Clearing up the confusion: minimizing postoperative delirium

Lionel Lim, MD, MPH, FACP, FACPM

Postoperative delirium is an under-diagnosed yet common geriatric syndrome that manifests as an acute confusional state, typically within 48 to 72 hours after surgery.  Occurrence of postoperative delirium is variable (15-25% in elective surgery) and its incidence is highest in hip and coronary artery bypass surgeries (>50%).¹  Delirium in elderly patients is associated with increased mortality, hospital length of stay, institutionalization, and dementia.^{2, 3}  Furthermore, functional and cognitive impairment from delirium may persist for months after discharge from hospital.¹  Risk factors for delirium are older age, neurocognitive impairment, multiple comorbidities, functional and sensory impairments, male gender and alcoholism.¹  Patients should be screened for risk factors or cognitive impairment at baseline so that appropriate delirium-preventing interventions can be implemented. 

It is also important to educate the patient and family regarding the etiology, treatment and prognosis of delirium.  Informing family that delirium is not permanent and may take weeks to months to eventually resolve may help to reduce anxiety or frustration.  Having the support and continued presence of family members or caregivers can also help patients during their recovery by providing frequent orientation, reassurance, and avoiding the need to institute unfamiliar “sitters” or physical restraint use during episodes of confusion.  Providers should pay close attention for delirium occurrence in previously affected or high-risk patients by using a validated screening tool like the Confusion Assessment Method (CAM).⁴  Appropriate steps should be taken to avoid the precipitants mentioned above and to correct and treat any underlying infective or metabolic derangements.  

Patients at high risk of post-operative delirium should be followed closely by an interdisciplinary team that is knowledgeable in the prevention, detection and management of delirium.  This team should include a geriatrician or internist working in a setting with established protocols in place to reduce the risk of postoperative delirium.⁵  These protocols would include adequate postoperative pain management, early mobilization, close monitoring of fluid status to avoid dehydration, adequate cognitive stimulation to maintain orientation, maintenance of diurnal rhythm through nonpharmacologic sleep protocols, bowel regimens to avoid constipation, minimizing the use of bladder or vascular catheters, and avoiding deliriogenic medications (benzodiazepines or sedatives and highly anticholinergic medications, e.g. diphenhydramine).  Implementation of the Hospital Elder Life Program (HELP) which targets some of the above risk factors and includes a nonpharmacologic sleep protocol in hospitalized older adults has been shown to reduce the risk of delirium by over a third.⁶  Although haloperidol for postoperative delirium prophylaxis may be a promising agent for use in high risk patients, larger trials are needed before their routine use can be justified in higher-risk patients.^7-9

References

1.            Marcantonio ER. In the clinic. Delirium. Ann Intern Med. Jun 7 2011;154(11):ITC6-1 to 6-16.

2.            Inouye SK. Delirium in older persons. N Engl J Med. Mar 16 2006;354(11):1157-1165.

3.            Witlox J, Eurelings LS, de Jonghe JF, Kalisvaart KJ, Eikelenboom P, van Gool WA. Delirium in elderly patients and the risk of postdischarge mortality, institutionalization, and dementia: a meta-analysis. Jama. Jul 28 2010;304(4):443-451.

4.            Inouye SK, van Dyck CH, Alessi CA, Balkin S, Siegal AP, Horwitz RI. Clarifying confusion: the confusion assessment method. A new method for detection of delirium. Ann Intern Med. Dec 15 1990;113(12):941-948.

5.            Marcantonio ER, Flacker JM, Wright RJ, Resnick NM. Reducing delirium after hip fracture: a randomized trial. J Am Geriatr Soc. May 2001;49(5):516-522.

6.            Inouye SK, Bogardus ST, Jr., Charpentier PA, et al. A multicomponent intervention to prevent delirium in hospitalized older patients. N Engl J Med. Mar 4 1999;340(9):669-676.

7.            Girard TD, Pandharipande PP, Carson SS, et al. Feasibility, efficacy, and safety of antipsychotics for intensive care unit delirium: the MIND randomized, placebo-controlled trial. Crit Care Med. Feb 2010;38(2):428-437.

8.            Kalisvaart KJ, de Jonghe JF, Bogaards MJ, et al. Haloperidol prophylaxis for elderly hip-surgery patients at risk for delirium: a randomized placebo-controlled study. J Am Geriatr Soc. Oct 2005;53(10):1658-1666.

9.            Wang W, Li HL, Wang DX, et al. Haloperidol prophylaxis decreases delirium incidence in elderly patients after noncardiac surgery: a randomized controlled trial*. Crit Care Med. Mar 2012;40(3):731-739.

How to Decrease Your Risk of Dementia with Cognitive Activities

Daviglus ML, Plassman BL, Pirzada A, et al. Risk Factors and Preventive Interventions for Alzheimer Disease: State of the Science. Arch Neurol. 2011;68(9):1185-1190.

·         Four cohort studies on the association between cognitive engagement and development of AD:

o   In all 4 studies, participants had normal cognition at baseline, and self-reported frequency of involvement in specific activities was assessed

o   All 4 studies showed a somewhat decreased risk of AD associated with greater involvement in cognitive activities.

Study 1

Verghese J, Lipton RB, Katz MJ,  et al.  Leisure activities and the risk of dementia in the elderly.  N Engl J Med. 2003;348(25):2508-2516
PubMed  |  Link to Article

·         Participation in leisure activities is associated with a reduced risk of dementia.

1.       reading,

2.       playing board games,

3.       playing musical instruments, and

4.       dancing.

·         Increased participation in cognitive activities at base line was associated with reduced rates of decline in memory.

Study 2

Akbaraly TN, Portet F, Fustinoni S,  et al.  Leisure activities and the risk of dementia in the elderly: results from the Three-City study.  Neurology. 2009;73(11):854-861
PubMed  |  Link to Article

·         Cognitively stimulating leisure activities may delay the onset of dementia in community-dwelling elders.

·         Cognitive activities in which seeking or processing information plays a central role.

1.       Doing crosswords,

2.       playing cards,

3.       attending organizations,

4.       going to cinema/theater, and

5.       practicing an artistic activity

Study 3

Wilson RS, Mendes De Leon CF, Barnes LL,  et al.  Participation in cognitively stimulating activities and risk of incident Alzheimer disease.  JAMA. 2002;287(6):742-748
PubMed  |  Link to Article

·         Frequent participation in cognitively stimulating activities is associated with reduced risk of Alzheimer’s disease.

·         7 common activities that involve information processing as a central component:

1.       viewing television;

2.       listening to radio;

3.       reading newspapers;

4.       reading magazines;

5.       reading books;

6.       playing games such as cards, checkers, crosswords, or other puzzles; and

7.       going to museums.

Study 4

Wilson RS, Scherr PA, Schneider JA, Tang Y, Bennett DA. Relation of cognitive activity to risk of .developing Alzheimer disease.  Neurology. 2007;69(20):1911-1920
PubMed  |  Link to Article

·         Level of cognitively stimulating activity in old age is related to risk of developing dementia.

·         More frequent participation in cognitive activity was associated with reduced incidence of AD.

·         Frequent cognitive activity was also associated with reduced incidence of mild cognitive impairment and less rapid decline in cognitive function.

·         Common activities in which seeking or processing information played a central role:

1.       reading a newspaper,

2.       playing games like chess or checkers,

3.       visiting a library, or

4.       attending a play

More on atrial fibrillation & anticoagulation

Excellent review article on the newer anticoagulants for stroke and systemic embolism reduction in AF:

ACP Journal Club 18 Sept 2012

 

The CHA₂DS₂-VASc score identifies those patients with atrial fibrillation and a CHADS₂ score of 1 who are unlikely to benefit from oral anticoagulant therapy 

European Heart Journal Oct 2012

 

Various risk stratification schemes predict ischemic stroke and bleeding in atrial fibrillation

ACP Journal Club 16 Oct 2012

Friberg L, Rosenqvist M, Lip GY. Evaluation of risk stratification schemes for ischaemic stroke and bleeding in 182 678 patients with atrial fibrillation: the Swedish Atrial Fibrillation cohort study. Eur Heart J. 2012;33:1500-10.

The CHA₂DS₂-VASc score had 100% sensitivity and 6% specificity for predicting stroke in patients with atrial fibrillation; CHADS₂ and Framingham scores had slightly lower sensitivities but higher specificities.

Commentary: In their analysis of 7 risk stratification schemes, Friberg and colleagues found that CHADS_2, CHA₂DS₂-VASc, and Framingham were the most accurate for predicting ischemic stroke, with c-statistics of 0.66 to 0.67. They also concluded that the 2 risk stratification schemes for bleeding had “similar predictive value,” but HEMORR₂HAGES had a higher c-statistic than the HAS-BLED scheme in 7 of 8 subgroups and the same value in 1 subgroup. A new risk stratification scheme, ATRIA (Anticoagulation and Risk Factors in Atrial Fibrillation), was not evaluated (1).

Warfarin-associated major hemorrhage predicted by 7 risk stratification schemes in patients with atrial fibrillation
ACP Journal Club 15 Nov 2011

The ATRIA risk score has the potential to be a major clinical tool but needs further validation in other populations and comparisons with similar risk scores, such as HAS-BLED (2).

 ATRIA risk score had a similar c-statistic (0.69) to HEMORR2HAGES (0.67).

 

Patients at High Risk for Falls: A Reason Not to Anticoagulate?
(from Journal Watch)

Donzé J et al. Risk of falls and major bleeds in patients on oral anticoagulation therapy. Am J Med 2012 Aug; 125:773

Among patients taking anticoagulants, high risk for falls was not associated with elevated risk for major bleeding.
Despite the proven benefits of oral anticoagulants in preventing and treating certain cardiovascular and cerebrovascular diseases, they are underprescribed. Fear of falls is the most commonly cited reason. Prior studies suggest that high fall risk should not be a contraindication to oral anticoagulant use, but these studies were limited by retrospective design or exclusion of patients at high risk for falls.
Researchers evaluated whether fall risk is associated with risk for major bleeding in a prospective study of 515 patients (median age, 71) who were treated with vitamin K antagonists at a hospital in Switzerland. Patients were considered to be at high risk for falls if they answered yes to either of two validated questions: (1) Did you fall during the last year? (2) Did you notice any problem with gait, balance, or mobility? Sixty percent of patients were categorized as high risk and all others as low risk. Times to first major bleeding event (including fatal or intracranial) within the 12-month follow-up did not differ significantly between the groups. Polypharmacy was associated independently with risk for major bleeds, with a 12% increase in risk for each additional drug taken.
Comment: This study adds to evidence that patients should not be denied oral anticoagulation solely on the basis of high risk for falls. For patients with valid indications for anticoagulation, benefit generally outweighs risk. For example, an analytic model suggests that older patients (age, 65) who have a 5% annual risk for stroke (i.e., CHADS₂ score of 2–3) and are taking anticoagulants would need to fall approximately 295 times yearly for risks of fall-related subdural hemorrhages to outweigh benefits of stroke prevention (Arch Intern Med 1999; 159:677). In addition, providers should be aware of risks conferred by polypharmacy in patients taking anticoagulants and should discontinue unnecessary medications, monitor patients more closely, or both.

CHF Prognostication

I favor the model described by Lee et al in the following study:

Predicting Mortality Among Patients Hospitalized for Heart Failure

JAMA.2003;290(19):2581-2587.

ACP Journal Club Commentary.

The actual risk prediction tool uses easily obtained variables (e.g. Age • Respiratory rate • Systolic blood pressure • Blood urea nitrogen • Serum sodium • Comorbid conditions: cerebrovascular disease, dementia, chronic obstructive pulmonary disease, cirrhosis, cancer, anemia) and the 30d. and 1 year risk score can be computed online:

http://www.ccort.ca/Research/CHFRiskModel.aspx

It has also been validated in populations in the US. 

Risk categories (score)	30-day mortality rate		1-year mortality rate
	Derivation	Validation	Derivation	Validation
Very low ( 60)	0.4%	0.6%	7.8%	2.7%
Low (61 to 90)	3.4%	4.2%	12.9%	14.4%
Intermediate (91 to 120)	12.2%	13.7%	32.5%	30.2%
High (121 to 150)	32.7%	26.0%	59.3%	55.5%
Very high (> 150)	59.0%	50.0%	78.8%	74.7%

A more recent article uses the same model to provide a median survival based on the risk scores above:

Life expectancy after an index hospitalization for patients with heart failure: a population-based study.

Am Heart J. 2008 Feb;155(2):324-31. PubMed PMID:18215604.

  

Table II. Mortality and life expectancy for all patients with HF according to the EFFECT HF risk score

	No. of patients	1-y mortality, n (%)	5-y mortality, n (%)	Median survival		Median survival for patients who survived first 3 m after hospitalization
				Months	95% CI	Months	95% CI
All patients with HF	9943	3294 (33.1%)	6833 (68.7%)	29	28-30	41	40-43
Baseline risk⁎
Very low	490	41 (8.4%)	117 (23.9%)	NA	NA	NA	NA
Low	3101	502 (16.2%)	1573 (50.7%)	59	55-62	66	63-71
Intermediate	4225	1450 (34.3%)	3185 (75.4%)	25	24-27	33	32-35
High	1770	1034 (58.4%)	1618 (91.4%)	8	7-9	18	17-20
Very high	357	267 (74.5%)	340 (95.2%)	3	2-4	12	10-15

NA, Not available.

Table IV. Mortality and life expectancy for patients with HF who had LVEF of ≤30% according to the EFFECT HF risk score

	No. of patients, n	1-y mortality, n (%)	5-y mortality, n (%)	Median survival		Median survival for patients who survived first 3 m after hospitalization
				Months	95% CI	Months	95% CI
All patients	1,467	489 (33.3%)	966 (65.8%)	31	27-35	46	42-49
Baseline risk⁎
Very low	131	16 (12.2%)	32 (24.4%)	NA	NA	NA	NA
Low	498	89 (17.9%)	252 (50.6%)	59	51-67	66	60-NA
Intermediate	559	207 (37.0%)	423 (75.7%)	22	19-27	32	28-36
High	225	140 (62.2%)	210 (93.3%)	6	4-9	18	14-21
Very high	54	37 (68.5%)	49 (90.7%)	3	2-8	14	7-24

 

Also useful is the EPERC FAST FACTS on CHF Prognostication and the Readmission Risk Calculator for CHF (also includes MI and Pneumonia).

The Central Role of Prognosis in Clinical Decision Making

JAMA Network | JAMA: The Journal of the American Medical Association | The Central Role of Prognosis in Clinical Decision Making

Physicians should be trained to consider prognosis in their clinical decision making. As a starting point, age-, sex-, and race-specific life expectancies (median and interquartile range) can be calculated using data from standard life tables.
Physicians could then make qualitative judgments, based on information from the medical record or clinical assessment, about whether a patient is likely to live substantially longer or shorter than an average person in his or her age and race cohort. The strongest and most consistent predictors of mortality in older persons include comorbidity and functional status. Lung disease requiring regular use of corticosteroids or supplemental oxygen, New York Heart Association class III or IV congestive heart failure, renal disease requiring dialysis, advanced dementia, inability to walk more than a block, and need for personal assistance with bathing are examples of factors that would reduce life expectancy substantially below the average.
The absence of significant comorbid conditions or functional limitations would identify older persons who are likely to live longer than average.

Antipsychotics and Mortality in Dementia

PsychiatryOnline | American Journal of Psychiatry | Antipsychotics and Mortality in Dementia
Commentary on Kales study Am J Psychiatry 2012;169:71-79

The study examined the relative risk of mortality associated with newly commenced prescriptions of olanzapine, quetiapine, and haloperidol, compared with risperidone as the reference compound, in a cohort of more than 30,000 veterans with dementia, ages 65 years and older.

Which antipsychotic has the highest and lowest risk of mortality?

Haloperidol was associated with significantly greater mortality than risperidone (relative risk=1.54).
Several studies have suggested that haloperidol confers a greater mortality risk than atypical antipsychotics (9), but the Kales et al. report is one of the few to have systematically compared mortality risk between different atypical antipsychotic agents.
Olanzapine and risperidone had similar mortality risk, while the risk for quetiapine was significantly lower (relative risk=0.73).
A key observation is that the highest increase in mortality risk was in the first 120 days, particularly in the first 30 days for haloperidol.

Which antipsychotic is best for aggression, agitation, or psychosis?

...three randomized controlled trials of quetiapine did not demonstrate any effectiveness in the treatment of aggression, agitation, or psychosis (4, 5).
The best evidence of efficacy is for risperidone, with consistent evidence of a modest but significant benefit over 12 weeks in the treatment of both aggression and psychosis.
There is also evidence of a similar level of benefit with aripiprazole, olanzapine, and haloperiodol, but only a few studies have examined other agents.
Through balancing the mortality data from this study and efficacy data from previous randomized controlled trials, risperidone and olanzapine emerge as the best evidence-based options.

What harms are associated with antipsychotic use?

...extrapyramidal symptoms, sedation, gait disturbances, and falls.
Many agents also lead to anticholinergic side effects, including delirium (4).
Tardive dyskinesia with atypical antipsychotics appears to occur less frequently than with typical antipsychotics, but QTc prolongation has been reported as a significant problem associated with several atypical antipsychotics.
A meta-analysis also identified a significant increase in respiratory and urinary tract infections as well as peripheral edema in people treated with risperidone, compared with placebo (4). These are likely to be class effects of atypical antipsychotics.
It has also become clear that other, more serious adverse outcomes, such as stroke and related cerebrovascular events, accelerated cognitive decline, and death, are significantly increased in people with dementia who are prescribed antipsychotics, compared with people with dementia not treated with these agents.
Deaths related to bronchopneumonia, thrombo-embolic events (including stroke and pulmonary embolism), and sudden cardiac arrhythmias are all significantly increased in people with dementia receiving antipsychotic treatment (6).
...meta-analyses of randomized controlled trials have reported significant incidence of sedation, chest-infection, and dehydration (4)

1.5- to 1.7-fold increase in mortality risk for people with Alzheimer's disease receiving antipsychotics

What can we do to reduce the harms associated with antipsychotic use?

...monitoring fluid intake and promoting vigilance for early detection and treatment of chest infections, may offer important potential opportunities to reduce excess mortality.
The potential role of ECG monitoring for prolonged QTc interval should perhaps also be considered

What about the use of non-psychotics like valproic acid?

The mortality risk for valproic acid and its derivatives, which were included as a nonantipsychotic comparison, was generally higher than the risk for quetiapine and similar to that for risperidone.

See guidelines below from UK Alzheimer's Society:

Optimising treatment and care for behavioural and psychological symptoms of dementia: A best practice guide