CPR+Post-Op+Delirium

__**Research Question:**__ Can preoperative factors be used to predict post-operative delirium?

"Delirium is an acute confusional state characterized by fluctuating symptoms including inattention, disturbances of consciousness, or disorganized thinking. Delirium is associated with greater cost, longer lengths of stay, complications, poor recovery, institutionalization, and mortality."


 * Type of surgery/reason for admission || Incidence of delirium ||
 * Hip fracture || 21.7% (4% to 53%) ||
 * Elective hip or knee replacement || 12.1% (9% to 28%) ||
 * Cardiac surgery || 32% (0% to 73%) ||
 * Major elective surgery || 10% (9% to 17%) ||
 * Elective vascular surgery || 34.5% (29% to 39%) ||
 * ICU care (surgical & medical patients >65 yo) || 70% to 87% ||

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The first CPR based on post-operative delirium is called Marcantonio’s CPR. This CPR does not include cardiac surgeries. This CPR states that the main factors that can predict post-operative delirium are age older than 70, alcohol abuse, a Telephone Interview for Cognitive Status (TICS) score less than thirty, a Specific Activity Scale (SAS) class IV, preoperative sodium 150 mmol/L, preoperative potassium 6 mmol/L, and glucose <3.3 or >16.7 mmol/L, and those with surgeries for aortic aneurysms or noncardiac thoracic procedures. The second CPR based on post-operative delirium focused on hip-surgeries. This CPR found that age, Mini-Mental State Examination score (MMSE) <24, visual acuity defined as binocular near vision worse than 20/70 after correction, Acute Physiological and Chronic Health Evaluation II score (APACHE II) >16, a higher Geriatric Depression scale score, and if it was an acute admission (fracture) were factors that helped predict post-operative delirium. **Factors that could predict delirium:**__**Age, Gender, and Visual/Hearing Impairments**__//__ Age __// With an aging population, complications specifically related to the elderly are becoming increasingly important. The US population is aging rapidly and by 2020, 53% of individuals will be older than 65 years.Estimates suggest that 55% of all operations are currently performed in patients older than 65 years. Given that the average 75 year old American “has three chronic conditions and uses five prescription drugs,” it’s not surprising that post-operative delirium is a frequent complication of surgery in elderly patients, with reported incidence rates ranging from 9% in patients over 50 and older who have undergone elective noncardiac surgery to nearly 18% in patients over the age 65 who have undergone emergency surgery and as high as 87% among elderly patients in ICUs.

In a 2009 study by Robinson stated that age was a risk factor for post-operative delirium. The average age was 64 __ + __ 9 years and 140 (97%) subjects were men. The incidence of delirium was 44% (64/144). The time to first onset of delirium was 2.4 __ + __ 1.9 days, and the mean duration of delirium was 4.0 __ + __ 5.1 days. No underlying cause of delirium was identified in 88% (56/64) of subjects who developed delirium. Identifiable causes of delirium in the other 12% (8/64) included: sepsis 75% (6/8), stroke 13% (1/8), and alcohol withdrawal 13% (1/8). The incidence of delirium increased as the subjects age by decade increased: age 50 to 59 years–incidence delirium 22% (11/50), age 60 to 69 years–incidence of delirium 42% (24/57), age 70 to 79 years–incidence of delirium 72% (18/25), and age 80 to 89 years–incidence of delirium 92% (11/12).

According to a study in 1993 by Inouye about a predictive model for hospitalized elderly patients based on admission characteristics, in contrast to results from previous studies, older age was not a statistically significant independent predictor of delirium. This finding may be attributable to the age cutoff (>70 years) among the patients and the relatively narrow age range that was represented or to better adjustment for other age-related factors such as illness severity.

In 1994, Marcantonio and colleagues also evaluated a clinical prediction rule for postoperative delirium using data available to clinicians preoperatively. Postoperative delirium occurred in 117 (9%) of the 1341 patients undergoing major elective noncardiac surgery. Independent correlates included age 70 years or older; self-reported alcohol abuse; poor cognitive status; poor functional status; markedly abnormal preoperative serum sodium, potassium, or glucose level; noncardiac thoracic surgery; and aortic aneurysm surgery.

In a 2012 study, age was dichotomised using a cut-off of 85 years, a value that was found to have a sensitivity of 85% and a specificity of 56% for delirium by the ROC curve analysis. In this prospective study, they identified three independent predictive factors for delirium: being 85 years old or older, being dependent in five or more ADL (of the six considered), and taking psychotropic drugs (antipsychotics, benzodiazepines, antidepressants, anticonvulsants and/or antidementia drugs). With these factors they developed a clinical prediction rule in which an individual risk score for delirium is obtained by adding one point for each of the factors present. Applying this rule, patients are classified as positive if they have a total score of 1 or more.

Ansaloni and colleagues studied 351 patients over the course of 357 surgical admissions, they found that five clinical factors were significant predictors of post-operative delirium and age over 75 was the first one. In a prospective descriptive survey of 71 patients ages 65 or older who were undergoing elective abdominal surgery, univariate analysis showed age over 74, longer ICU stay, longer hospital stay, greater number of postoperative complications, low preoperative cognitive screening test scores, and higher intraoperative American Society of Anesthsiologists scores to be significant risk factors for postoperative delirium. After multivariate analysis, however, only age over 74 was significant.

//__ Gender __// Male gender is a clinical risk factor for postoperative delirium. In a study by Fisher and Flowerdew, which was a simple model for predicting postoperative delirium in older patients undergoing elective orthopedic surgery, demonstrated that males were at greatest risk for postoperative delirium. In a study by Edlund about delirium before and after femoral neck fracture, male patients were more delirious preoperatively and postoperatively.

//__ Hearing Impairments __// A presence of sensory impairment increases the chance of falls and hip fractures, which can lead to postoperative delirium. In the 1993 study by Inouye, patients were considered to have hearing loss if they heard fewer than three of eight tones on the audioscope test (tones at a hearing level of 40 dB and at frequencies of 500, 1000, 2000, and 4000 Hz), had a score of 4 of 8 or less on the questions screening for hearing loss or wore a hearing aid. For assessment of hearing, the Whisper test was used. Hearing impairment was defined as present if the patient heard correctly fewer than 7 of 12 numbers on the Whisper test or wore a hearing aid. The Whisper test at a distance of two feet from the patient was the most discriminant test with a sensitivity of 100%, a specificity of 84% and a predictive value of 92% for hearing impairment likely to benefit from provision of a hearing aid. Free-field voice testing appears a simple, reliable and reproducible test for detecting hearing impairment in elderly patients. media type="custom" key="25581252"

//__ Visual Impairments __// In the study by Inouye, vision impairment was identified as one of the four baseline risk factors for delirium. The other risk factors were severe illness, dehydration, and preexisting cognitive impairment. Patients were considered to have vision impairment if their corrected vision was worse than 20/70 on both near and distant binocular tests (Jaeger type test). One in four adults over the age of 75 have 20/70 vision. This type of low vision can be loss of central vision, loss of peripheral vision, night blindness, blurred vision, and hazy vision. Vision impairment had a high risk from delirium but a low prevalence in the cohort. In a study by Runge, the Jaeger type test is the gold standard for reading vision tests. Picture below represents 20/70 vision.



__**Pre-existing Cognition Impairments**__

Post-operative delirium is consistently associated with pre-operative cognitive impairments and past history of delirium or confusion. Recognizing the presence of these factors may not be as obvious or previously documented like other risk factors, but can provide important information about patients’ risk of developing delirium post-op. Several articles including, Freter et al found cognitive impairment to be associated with POD development in a univariate analysis (OR=6.96, 95% CI=2.41-20.07)

__//Prior history of Delirium//__
====Present delirium, even subtle periods of confusion can be major indicators for post-operative delirium and should be taken into account when determining the POC. Lee et al (2011) had similar results between the two groups created using predisposing risk factors for POD. There was “substantially higher” POD development in patients who had preoperative delirium and were in the Probable Dementia Group, than those without preoperative delirium in the No Dementia Group (54% vs. 26%; p≤0.001; OR=3.35). ==== Edlund et al (2001) found that of 30 patients (29.7% of sample) who were delirious prior to surgery, all but one remained delirious post-op. Patients with preoperative delirium are linked to poorer short-term and long-term outcomes compared to patients with only POD (18.8%). Patients who showed signs of delirium prior to orthopedic procedure also had longer recovery and more complications than some one who developed post-operative delirium. History of delirium patients was also commonly sent to an institutionalized care center upon discharge.

====__//Pre-operative attention deficits//__ were found to be predictive of POD by Lowery et al (2007). Slower mean reaction times, as well as increased variability in reaction times showed to be associated with POD. Researchers did not describe specific tests to evaluate reaction times, which was a limitation of the study. However, they stated that greater variability in reaction times, one standard deviation above the mean, put the subject at 4-5 times more risk of developing POD.

__//Previous education//__
====Lower education level was named a risk factor for POD in the multivariate analysis (OR=3.59, 95% CI=1.14-11.25). These subjects were categorized by only having an elementary level education.

**//MMSE - Mini-Mental State Exam//**
====Pre-op cognitive impairment is an “important predictor or post-op delirium,” and MMSE is a valuable tool to evaluate it. Freter et al (2005) stated that it can be used to target patients who are at increased risk upon arrival at the orthopedic unit. Galanakis et al (2001) MMSE was used to measure prior cognitive impairment, mean score was 26.8 (±3.6) (OR=1.32 for each point less, 95% CI=1.07-1.22). They found that subjects who developed POD had significantly lower MMSE scores (//p<//0.05) preoperatively, with 20 out of 25 of the POD subjects with a score less than 24 (out of 30).(Galanakis, 2001). Lee et all (2011) also found the probable [development of] dementia group had significantly lower MMSE scores compared to the no dementia group; 18.6 mean score vs. 27.4 (//p//<0.001). This study also used MMSE to diagnose POD in addition to the Confusion Assessment Method or CAM.(Lee, 2011).



** TICS - Telephone Interview for Cognitive Status ** Marcantonia et al used TICS to evaluate preoperative cognitive status and was described as a modified, verbal version of MMSE. TICS is scored 0-41, with 30 or below being considered having cognitive impairment. During this study they adminstered TICS in person, but were able to use the same test to follow up via telephone post-op. Out of 1341 subjects, 24% (30/127) subjects who scored less than 30 on TICS developed POD. There was also 47/732 (6%) of subjects who scored greater than 30 who also developed POD. TICS was found to be a good measure for cognitive status and was a significant risk factor for POD.

**//Clock-drawing//**
==== The clock-drawing test is used to provide a baseline of cognitive ability prior to procedure. Scores less than 6 put pre-operative orthopedic patients at risk for POD. A literature review by Shulman (2000) found the clock-drawing test to have high sensitivity (85%) and specificity (85%). It also had high inter-rater and test-re-test reliability levels. One concern is that inconsistent scoring systems may affect reliability, but this variability was still found to result in similar outcomes. The clock drawing test has “good” predictive validity and is sensitive to cognitive changes. Clock-drawing Test PDF

//__Depression__//
====Depression, although considered more mental health than cognitive impairment, has also been linked to delirium after operation and hospital stay. Galanakis et al (2001) results showed 20.2% of POD subjects had depression (OR=3.67, 95% CI=1.12-12.02). ====Depression was considered a single/univariate risk factor in a systematic review by Dasgupta et al (2006). 50% of the articles used in the review measured depression using a depression scale or formal measure prior to noncardiac surgery. Several of these articles included other psychiatric illness along with depression and history of depression (1).==== __**Co-Morbidities**__ - Review by Dasgupta and Dumbrell, 2006 Comorbidity measured by: ~ Charlson Comorbidity Index [] ~ Counts of medical conditions ~ Modified RAND Index (in statistics, used to measure similarity between two data clusterings) Findings: ~ Not enough data available in the Charlson Comorbidity Index studies ~ 2/3 studies analyzed for studies using counts: __relationship suggested between increasing number of conditions and delirium (P<.001)__

- Review by Noimark, 2009 ==== "Co-morbidity: Older people undergoing surgical treatment often have comorbidity. Several studies have identified that having a number of unspecified co-morbid problems, including a previous episode of delirium, increases the risk of POD. Interestingly, __conditions which either increase vascular risk or indicate vascular damage are shown to increase risk of POD__.” ==== ▪ Hypertension  ▪ Diabetes mellitus  ▪ Myocardial infarction  ▪ Stroke  ▪ Atrial fibrillation  ▪ Peripheral vascular disease  ▪ Heart failure  ▪ Previous amputation

- Study from Schuurmans et al., 2003 ▪ Presence of 4 or more comorbidities is a risk factor ▪ “The delirious and non-delirious subjects did not differ much in comorbidities before the fracture, except in psychiatric comorbidities (//p// < .006) and the total number of comorbid problems (//p// < .02).”  Table 3. Comorbidity and Number of Medications of Non-delirious (n = 74) and Delirious (n = 18) Hip Fracture Subjects ∗Significant //p// value.  †Hypnotics, sedatives, anxiolytics, antipsychotics, lithium, anti-depressants.
 * || Non-delirious (%) || Delirious (%) ||
 * Comorbidity ||  ||   ||
 * Haematological || 4 (5.4) || 1 (5.6) ||
 * Neurologic || 9 (12.2) || 4 (22.2) ||
 * Motion || 27 (36.5) || 9 (50.0) ||
 * Cardiovascular || 35 (47.3) || 10 (55.5) ||
 * Pulmonal || 19 (25.7) || 3 (16.7) ||
 * Gastrointestinal || 26 (35.2) || 6 (33.3) ||
 * Urogenital || 22 (29.7) || 8 (44.4) ||
 * Endocrinological || 10 (13.5) || 1 (5.6) ||
 * Skin || 4 (5.4) || 3 (26.7) ||
 * Psychiatric [|__∗__] || 17 (23.0) || 10 (55.5) ||
 * Number of comorbid problems ||  ||   ||
 * 0 || 4 (5.4) ||  ||
 * 1–3 || 55 (74.3) || 11 (61.1) ||
 * 4–7 || 15 (20.3) || 7 (38.9) ||
 * Mean (//SD//) [|__∗__] || 2.6 (1.6) || 3.4 (1.4) ||
 * Number of medications ||  ||   ||
 * Range || 0–13 || 0–15 ||
 * 0 || 14 (18.9) || 2 (11.1) ||
 * 1–2 || 19 (25.6) || 5 (27.8) ||
 * 3–5 || 28 (37.8) || 3 (16.7) ||
 * 6–10 || 10 (13.5) || 4 (22.2) ||
 * >10 || 3 (4.1) || 3 (16.7) ||
 * Mean (//SD//) || 3.4 (3.1) || 5.1 (4.4) ||
 * Use of psycho-active drugs [|__†__] || 27 (36.5) || 10 (55.6) ||

- Prospective study by Lee et al., 2011 ▪ Compared risk factors of post-op hip surgery patients with and without dementia: significance in number of medical comorbidities in the without dementia group (not significant in the group with dementia) (OR: 1.15; 95% CI: 1.01-1.32) - Severe illness ▪Inouye, 1993 High risk indicated by an APACHE II score of greater than 16 or the nurse giving the rating of severe ~ APACHE II: Acute Physiology and Chronic Health Evaluation ~ [] ~ Used to predict hospital mortality ▪ Limitation: low prevalence (but relatively high risk for delirium), which could lead to unstable predictive estimates; needs to be further studied ▪ Adjusted Relative Risk of 3.5, CI of 1.5-8.2
 * |||| No Dementia (N=284) |||| Probable Dementia (N=141) ||
 * || Crude OR (95% CI) || p-value || Crude OR (95% CI) || p-value ||
 * # # of medical comorbidities || **1.14 (1.03, 1.27)** || **0.023** || 1.09(0.95, 1.25) || 0.201 ||
 * CVA or TIA || 1.15 (0.77, 3.03) || 0.225 || 1.22(0.57, 2.59) || 0.613 ||
 * #of prescription meds || **1.32 (1.02, 1.70)** || **0.034** || 0.95(0.74, 1.20) || 0.651 ||
 * ASA rating 4 or above || **2.45 (1.12, 5.25)** || **0.022** || 1.30 (0.54, 3.14) || 0.555 ||
 * History of depression || 1.13 (0.53, 2.39) || 0.758 || (0.43, 2.26) || 0.919 ||
 * |||| Hospital Mortality (%)  ||
 * APACHE II Score || Non-operative || Operative ||
 * 0-4 || 4 || 1 ||
 * 5-9 || 8 || 3 ||
 * 10-14 || 15 || 7 ||
 * 15-19 || 24 || 12 ||
 * 20-24 || 40 || 30 ||
 * 25-29 || 55 || 35 ||
 * 30-34 || 73 || 73 ||
 * ≥35 || 85 || 88 ||

- Another study mentioned previously (Lee et al. ) that compared hip fracture repair patients with and without dementia showed that ASA PS scores above 4 in the non dementia group were significant risk factors. ▪ American Society of Anesthesiologists (ASA) physical status (PS) classification rating system:  __ ASA Physical Status Classification System __  ** ASA Physical Status 1 ** - A normal healthy patient  ** ASA Physical Status 2 ** - A patient with mild systemic disease  ** ASA Physical Status 3 ** - A patient with severe systemic disease  ** ASA Physical Status 4 ** - A patient with severe systemic disease that is a constant threat to life  ** ASA Physical Status 5 ** - A moribund patient who is not expected to survive without the operation  ** ASA Physical Status 6 ** - A declared brain-dead patient whose organs are being removed for donor purposes  []

Some other things that were noted in the systematic review by Dasgupta and Dumbrell were that smoking and BMI were not found to be associated with delirium, while there is a statistical association suggested between depression and delirium (P<0.001). Specific conditions were assessed in several studies, but they were not analyzed in this particular review. Inouye does suggest that coexisting health conditions including chronic renal or hepatic disease, a history of stroke, neurologic disease, metabolic derangements, terminal illness, and HIV are also predictive factors for the development of delirium in the elderly population.

**__Prior Function__**

__//Tests Used to determine levels of physical function://__ //SAS: Specific Activity Scale// A survey developed for individuals with cardiovascular dysfunction Ordinally scaled with a I being the best and IV the worst. Class I: can carry 24lbs up 8 steps Class IV: unable to walk 4 km/h for one block, make their bed, or dress themselves without stopping. __//A grade of a IV indicates severe limitation.//__

www.cebp.nl/vault_public/filesystem/?ID=1529‎
 * Patient can perform to completion ||  Patient cannot perform to completion or does not perform  ||  Specific Activity Scale Functional Class  ||
 * Any activity requiring >=7 metabolic equivalents ||  NA  ||  I  ||
 * Any activity requiring >=5 metabolic equivalents ||  Any activity requiring >=7 metabolic equivalents  ||  II  ||
 * Any activity requiring >=2 metabolic equivalents ||  Any activity requiring >=5 metabolic equivalents  ||  III  ||
 * NA ||  Any activity requiring >=2 metabolic equivalents  ||  IV  ||

**

** __//Barthel Index://__ [] ** ** This test rates people on their ability to get dressed independently, groom, eat, bathing, and level of ambulation. Lower scores indicate more functionally independent people. **

** //__What the Research Says:__// **

** One study identified preoperative factors for the development of delirium after noncardiac surgery, one being severe functional impairment, and developed a CPR. They measured functional impairment using the SAS. Of the 70 patients with a SAS of class IV, 17% developed postoperative delirium. Of the 802 patients with a SAS of I-III, 8% developed delirium. This shows a relative risk of 2.1 with a significance of P= .01. This study included a SAS score of IV as a factor in their CPR with a value of 1 point. According to this CPR if a patient has only severe functional impairment, with a SAS of IV, and none of the other factors, that person has an 8% chance of developing delirium after surgery. As apposed to people with none of the risk factors who have <1% chance of developing delirium with a noncardiac surgery. ** **

** In a review, looking at preoperative risk assessment for non-Cardiac patients, they only considered factors that were investigated by 2 or more studies. 7 out of the 25 studies investigated functional status. All of the 7 studies found a correlation between functional dependence and the development of delirium. The studies that used the Barthel index found a moderate amount of correlation between functional dependence and delirium P < .001. The studies that used the Specific Activity Scale had a weighted odds ratio of 1.88 with a CI of (1.25- 2.95) showing a small correlation to delirium. This study did conclude that functional impairment is factor correlating to post operative delirium, however it is not one of the most significant factors. ** **  ** In a study looking at preoperative risk factors for developing postoperative delirium, physical function was considered. This study looked at SAS scores of greater than or equal to 3 as an indicator of developing post-operative delirium. They found the relative risk to be 1.57 with a confidence interval of 1.27-1.94. This relative risk was the lowest among all of the other factors they studied. They still considered functional limitation to be significant. ** **  ** Another study aimed at developing a list of reliable characteristics for predicting delirium in elderly who are hospitalized, also looked at decreased physical function. Although this study is not specifically aimed at post-operative patients, many of the factors are similar. This study had a very small sample size, but they did find a moderately significant relationship between physical function and the development of delirium. 36% of the 28 people that needed assistance with one or more ADL developed delirium. Conversely, of the 78 that did not have difficulty with at least one ADL, 22% still developed delirium. This shows that the functional limitation does predict slightly higher chances of developing delirium. For those that needed assistance with two or more IADL’s (60), 32% developed delirium. Of the other 46 that did not need help with two or more IADL’s, 17% still developed delirium. Once again, this measure does show a slightly more likely chance of developing delirium in the presence of decreased physical function. The numbers obtained in this study were not significant enough to include decreased physical function as a factor in their predictive rule. ** Decreased physical function was found in some of the larger reviews to be a significant predictor of postoperative delirium. There is still a lot of research lacking on this factor and its relationship to the development of delirium. When it comes to the tests being used to analyze physical function, there is also a lack of consistency among the studies. The Specific Activity Scale was used most commonly, however there is a gap in the evidence for the validity of this scale in determining physical function levels.

** __Conclusion and Discussion__ **

Other factors commonly referred to and studied are psycholpathological symptoms, psychotropic drug use, alcohol use, smoking, BMI, institutional residence.

** __Resources__ **