Clinical+Prediction+Rule+for+Post-Operative+Delirium

Are there specific patient risk factors that can be used to predict postoperative delirium?
 * Clinical Question **


 * Background **

//**__ What is postoperative delirium? __**//

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Delirium is an acute change in mental status and attention that affects 11% to 42% of hospitalized patients. Although an acute condition, it can have adverse consequences. For example, patients with delirium are at increased risk for in-hospital complications and mortality, as well as greater likelihood of post-hospital, long-term consequences, including skilled care placement. Strategies to prevent delirium have been successful, particularly in patients at heightened risk,and multiple validated delirium prediction rules to identify patients' risk currently exist (13).

**//__How do you diagnose it?__//** (Assessments/Tools)

media type="youtube" key="6WyJ0zL7VkI" width="560" height="315" (Duration: 0:42 - 2:06) The most common assessment of postoperative delirium is the Cognitive Assessment Method (CAM) ICU test. Any more than 2 mistakes in the first section counts as a failure and “inattention.” This means the health care professional would proceed to the second part of the test (four questions and a command). If the patient makes two more mistakes, they are considered to have “disorganized thinking.” If a patient is considered to have inattention and disorganized thinking, they are CAM positive for delirium.

__Criteria for studies included:__ Subjects over 50 years old, looked at predictive factors of current CPR or for the development of new CPR’s, < 30 years old
 * Research **

__Sources used:__ Google Scholar, PUBMED

__Search terms:__ Clinical prediction rule, Delirium, Risk factors, Intraoperative factors, Cognition, Age, Alcohol use, Nutrition

Through the research, several clinical prediction rules were found. The most inclusive of multivariate risk factors was done by Wassenaar et al, in an article titled “Multinational development and validation of an early prediction model for delirium in ICU patients.” Using nine factors, the model they created allows for health care professionals to identify the patients that are most at risk for postoperative delirium after surgeries. The nine factors are reflected in Table 2, below.
 * Clinical Prediction Rule **



They divided the patients into four risk categories based on the factors listed above. These were the predicted probabilities for development of postoperative delirium: very low (0–10 %), low (10–20 %), moderate (20–35 %), and high risk for delirium (>35 %). The sensitivity and specificity of these categories to the outcomes are shown in the chart below (Figure 2, 17).

Note the positive likelihood ratio, and how it increases along with the predicted risk percentage.

__** PRE-OP COGNITION **** : **__ Three prospective cohort studies were referenced.
 * Risk Factors **
 * In a study with 2914 patients, multiple factors were statistically analyzed. Of those, patients with a history of cognitive impairment had the highest correlation with post-op delirium. The regression coefficient was 0.878 with an odds ratio of 2.406 at a 95% confidence interval. This high correlation due to the r value and the odds ratio greater than 2 strongly indicate a history of cognitive impairment as a predictive factor for post-op delirium (17).
 * In a study with 500 patients who had major surgeries (elective), the univariate preoperative risk factors were calculated. They are presented in Table 1. Those who scored less than 30 on the TICS (Telephone Interview for Cognitive Status) test were considered to have preoperative cognitive impairment. The TICS test is a modified (and validated) version of the Mini-Mental Status Examination, which is used often to determine cognitive status (8).
 * The MMSE ranges from 0-30, with 0 representing severely impaired cognition and 30 representing no impairments in cognition. The TICS test ranges from 0-41, and in this study, a score of less than 30 was considered indicative of cognitive impairment. Both examinations have the health care professional ask the patient person/place/time questions, and test their short term memory.

( 8 )
 * This shows several of the risk factors that are a part of the clinical prediction rule for delirium. Preoperative cognitive impairment has a calculated relative risk of 3.1, while a previous history of delirium has a relative risk of 4.1 (8). These combined previous cognitive issues demonstrate a high predictive factor for delirium post-op.
 * Of the 603 patients in the study, 74 developed delirium within 5 days post-op. The researchers were able to determine that the patients in the delirium group had a statistically significant difference in MMSE scores from the patients with no delirium. This means that those patients who had delirium had scored with significantly worse cognitive impairments (7).
 * The p-value for the same study was <.001 for those patients who scored less than 24 out of 30 on the MMSE, meaning that scores below 24 were significant for post-op delirium at the confidence interval of 99 percent (7).

(7)

__**Summary**__: It has been demonstrated that measurable cognitive impairments do increase a patient’s risk to develop postoperative delirium. The measures used to indicate cognitive impairments in these particular studies are a score of less than 24 on the MMSE and a score of less than 30 on the TICS. No studies included in this presentation attempted to determine physiological determinants, due to the wide range of variety and individuality in cognitive impairments. Not only are preexisting cognitive impairments a predictive factor for postoperative delirium, but they are one of the strongest predictive factors. For the prospective cohort studies that gathered this data, a history of cognitive impairments consistently had the highest or second highest relative risk factor, odds ratio and regression coefficient.

__** INCREASED AGE: **__
 * Age is the most commonly cited risk factor for post-op delirium
 * The prevalence of delirium has been estimated to be up to 70% in the critically ill elderly patients, and age 80 and above was found to be the most significant delirium predictor with a p value of <.001 (4).
 * Cognitive dysfunction (such as delirium), and vision and hearing impairment also have been found to be significant contributors to delirium. These factors are more likely to appear with advanced age (4).
 * A prospective study over 2 years with 603 patients (70 years and older) set out to determine patient risk levels based on a predefined list of delirium risk factors. The 74 patients who developed delirium had an average age of 81.8 +/- 6.7, compared to the age of the 529 that did not develop delirium 77.4 +/- 5.7 (7).




 * The p value for age was once again found to be <.001, producing a significant factor for delirium
 * Reduced vision was also assessed and found in 15 of the patients that developed delirium. The p value was significant producing a .03 value (7).
 * Contrary to previous findings, age was an independent predictive factor for delirium (7).

__**Summary:**__ Although it is difficult to pick a single reason for why age affects delirium rates, it is clear that age play a significant role in developing post op delirium and should always be considered when developing a clinical prediction rule. Additional factors that can accompany patients as they get older are cognitive dysfunction, and vision and hearing loss.

__** ALCOHOL USE / NARCOTICS: **__
 * A study looked to discover potential risk factors after joint arthroplasty for post op delirium. Results did show an increased odds ratio for history of alcohol abuse for the risk of delirium (14.009) but these were found to be insignificant with a p value of .183 ( 1 ).
 * Another study of over 1300 subjects looked at potential risk factors that could be identified easily preoperatively in order to create a simple prediction rule to evaluate the risk for post op delirium so that preventive intervention may be administered in order to reduce the risk of post op delirium. It was discovered that those who self reported alcohol abuse upon admission had a Relative risk of 2.4 and was found significant with a P value of .01 ( 9 ).
 * In a study that looked at those who underwent elective orthopedic surgery 500 consecutive subjects were asked a series of questions in order to help identify risk factors and come up with a new clinical prediction rule to predict episodes of delirium and length of stay. They found that when asked if the subject thought there alcohol consumption affected their health and adjusted odds ratio of 6.5 and if they were on oral narcotics an adjusted odds ratio of 2.7 was formed. Both of these ended up being used as questions in their clinical prediction rule ( 15 ).
 * Another study that looked at just under 3000 in order to try to identify risk factors that could predict post op delirium reported that if the patient reports any type of alcohol abuse in the past the odd ratio of them developing delirium post op was 1.657 ( 17 ).
 * This study contradicted most, in a study of 209 subjects those who reported drinking some form of alcohol’s risk of developing post op delirium was insignificant with an odds ratio of .79 and a P value of .6 making the findings insignificant ( 4 ).

__**Summary**__: Although it does seem apparent that alcohol consumption is a contributing factor to post op delirium, none of these studies seemed to define how much alcohol or how frequently the patients had been drinking whether it was right before their surgery or 30 years prior. It seemed that the phrasing of the question affected the outcome of those affected by alcohol use. More research needs to be looked into to more properly define what qualifies as alcohol use or abuse and if there is a time frame that it is relevant in. The population that is sampled from may also need to be looked into, whether it was a region or country that drinking is more common or more taboo to see if that makes a significant difference in the outcome. PT could suggest abstaining alcohol use prior to surgery if they see the patient early enough before surgery or to limit narcotic use.

__** NUTRITIONAL FACTORS: **__
 * Can poor nutritional status predict post-op delirium in elderly hip fracture surgery patients? Delirium and poor nutritional status are two common findings in individuals with hip fracture but is one a predictor of the other? Although delirium and poor nutritional status may coexist in an individual experiencing hip fracture, few studies have assessed the effect of their association on clinical outcomes.
 * Patients over 70 underwent a geriatric assessment including nutritional status, evaluated using the Mini Nutritional Assessment Short Form or MNA-SF. The MNA-SF is a validated tool to detect poor nutritional status that consists of six items: decline in food intake over the past 3 months, weight loss during the last 3 months, mobility, acute disease or psychological stress in the past 3 months, current neuropsychological problems, and body mass index (BMI)Malnourished is defined as a score between 0-7, At risk of malnutrition is defined as a score between 8-11, and well nourished is defined as a score from 12-14. There were 78 malnourished, 185 at risk of malnutrition, and 152 well nourished participants in the study. Those who were malnourished and at risk of malnutrition were more likely to develop postoperative delirium (11).
 * The conclusion is that this study shows that either risk of malnutrition or malnourishment are independent predictors of postoperative delirium. Therefore, nutritional status should be assessed in individuals before hip surgery to determine risk of developing delirium. Findings from this study would be clinically relevant because postoperative delirium is partially preventable, and poor nutritional status may be a target condition for intervention or prevention (11).
 * Possible complicating factors: All participants were over 70 with a hip fracture so it may not be applicable to all populations. Also the patients with poor nutritional status were also described as more disabled and more cognitively impaired than the well nourished and at risk of malnutrition groups. The study claims that multivariate regression analysis adjusted for age, sex, comorbidity, functional impairment, and preoperative cognitive status (11).






 * It is important to know whether we can predict the risk of postoperative delirium after orthopedic surgeries. It is a major cause of concern, especially for the elderly undergoing surgery. The MNA-SF is a leading way to assess nutritional status in patients. Can it be a predictor of postoperative delirium after surgery?
 * 544 individuals (60 and older) were included in this study. The MNA-SF was used to evaluate the patients’ nutritional status preoperatively. Delirium was assessed daily after surgery using the confusion assessment method (CAM). The 4th edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM) with text revisions criteria was used to confirm the diagnosis of delirium. Multivariate and univariate logistic regression analyses were performed to identify key factors associated with postoperative delirium. For multivariate analyses, variables were entered into a multiple logistic regression model to identify the most significant risk factors for developing postoperative delirium after orthopedic surgery (2).
 * Age, male gender, low Mini-Mental State Examination scores, and higher Charlson Comorbidity Index scores were associated with increased likelihood of postoperative delirium. After adjusting for all potential factors in the final model, participants that were at least at risk for malnutrition were 2.85 times more likely to develop postoperative delirium compared to well-nourished subjects (2).
 * The study concludes that the MNA-SF is an effective test and can be used as a tool to predict the possibility of postoperative delirium in elderly patients after orthopedic surgeries. Several studies have found that poor nutrition is associated with functional and cognitive impairment, dependency and increased risk of depression, all of which are documented risk factors for postoperative delirium. Use of this tool may enable early detection and timely intervention for patients who are at risk of malnutrition, potentially helping to prevent negative postoperative outcomes (2). Malnutrition can be indicated by low-serum albumin level as a quick test before going into surgery.

Multiple logistic regression of predisposing factors for incident POD after orthopedic surgery:


 * = ** Covariables ** ||= ** Adjusted OR ** ||= ** S.E. ** ||= ** β ** ||= ** P values ** ||= **95% CI**  ||
 * = Age  ||= 1.06 ||= 0.03 ||= 0.06 ||= < .05 ||= 1.01–1.11 ||
 * = Male gender  ||= 5.78 ||= 0.47 ||= 1.76 ||= < .001 ||= 2.30–14.55 ||
 * = MNA-SF: At risk for undernutrition (score 0–11)  ||= 2.85 ||= 0.45 ||= 1.05 ||= < .05 ||= 1.19–6.87 ||
 * = MMSE  ||= 0.84 ||= 0.04 ||= 0.17 ||= < .001 ||= 0.78–0.91 ||
 * = CCI  ||= 1.32 ||= 0.14 ||= 0.28 ||= < .05 ||= 1.01–1.73 ||

__**Summary:**__ Nutritional status, specifically evaluated by the MNA-SF, seems to be a very strong predictor of the development of postoperative delirium. However poor nutritional status often presents in patients with many health risks and comorbidities, and it can be difficult to determine the true cause and effect relationship among them. Overall, these studies support nutritional status as a strong, independent predictor of postoperative delirium.

__** INTRAOPERATIVE FACTORS: **__ When researching risk factors for postoperative delirium that come from the actual surgery itself there are many different aspects that have been researched. Below is information collected and summarized from a prospective cohort study that include some of the most commonly talked about possible risk factors.

1,341 patients, 50 years or older, were included in this study to help determine possible intraoperative risk factors that could lead to the development of postoperative delirium. Out of all of the subjects, postoperative delirium was diagnosed in 9%. Delirium was diagnosed on either postop day 2 or 3, and was done via daily interviews with the CAM, nursing intensity index, and data retrieved from the hospital’s medical records (10). *** Negligible difference in rates of delirium among specific types of anesthesia.
 * __**Route of Anesthesia**__: A common factor that shows up in studies researching risk factors for postoperative delirium is the particular route of anesthesia that was used during the surgery. This study found that the incidence of delirium specific to the particular anesthetic method is small enough that it is considered non-associative with developing delirium (the medications given in the postoperative period, particularly analgesics, are a more important factor) (10).
 * // **NOT** STATISTICALLY SIGNIFICANT //
 * **__Intraoperative Hypotension:__** (//see table below//)
 * Blood pressure decline to 66% of preoperative baseline (or <90mmHg)
 * Out of 352 of the subjects that had intraoperative hypotension, 27 of them developed postoperative delirium (8%.)
 * Out of 989 of the subjects that did **not** have intraopertaive hypotension, 90 of them still developed delirium (9%.)
 * The rates of delirium in subjects with and without intraoperative hypotension did not have a significant difference. Even if they did, the study explains that the incidence and duration of hypotension cannot be an __//independent//__ factor in determining if a patient will have postoperative delirium, because it is on the same causal train as the route of anesthesia (6, 10).
 * This was backed by evidence from an additional study that concluded their research with a sensitivity analysis where they performed additional adjustments to these variables and the results did not change from the initial conclusion (6).
 * // **NOT** STATISTICALLY SIGNIFICANT //


 * **__Bradycardia and Tachycardia__** (//see table below//)
 * **Bradycardia** (<60 bpm requiring atropine)
 * Rate of occurrence of postoperative delirium in patients that experienced intraoperative bradycardia was the same as patients who did not have bradycardia (10).
 * Out of 49 of the subjects in this study that experienced bradycardia, 4 of them developed postoperative delirium (8%.)
 * Out of 1292 of the subjects who did **not** experience bradycardia in surgery, 113 of them still developed postoperative delirium (9%.)
 * **Tachycardia** (>120 bpm for more than 5 mins)
 * As with bradycardia, the occurrence of postoperative delirium in patients that had intraoperative tachycardia was the same as patients who did not have tachycardia (10).
 * Out of 47 patients that experienced tachycardia during surgery, 5 of them developed postoperative delirium (11%.)
 * Out of 1294 patients that did **not** experienced tachycardia during surgery, 112 of them developed postoperative delirium (9%.)
 * // **NOT** STATISTICALLY SIGNIFICANT //




 * **__ Blood Loss and Number of Blood Transfusion __**
 * There is a significant association between blood loss and number of blood transfusions and the development of postoperative delirium.This study also found that low postoperative blood oxygen saturation was highly associated with delirium; blood loss and transfusions have major influences on blood saturation (10).
 * Blood transfusions were recorded from the start of surgery until the patient was discharged.
 * Mean blood loss during surgery was 566 +/- 890 cc.
 * Mean blood transfusion was 1.3 +/-2.4 units.
 * // STATISTICALLY SIGNIFICANT //



*** out of all 5 of these intraoperative factors, this was found to be the most indicative of developing delirium.
 * **__ Lowest Postoperative Hematocrit __**
 * There was no statistical significance in //preoperative// hematocrit level between patients who did not develop postoperative delirium and patients who did.
 * On the other hand, postoperative hematocrit was examined by using the lowest hematocrit level recorded postop at least 1 day before the onset of delirium (and throughout the whole postop period in patients who did not develop delirium.)
 * The risk for postoperative delirium was found to be associated when the patient’s hematocrit level was <30%.
 * The researchers believe that low hematocrit levels can lead to delirium by causing inadequate oxygen delivery to the brain - the same way that blood loss and transfusions can also possibly lead to delirium.
 * Despite knowing how low hematocrit levels affect the brain, and that low levels are a risk factor, it cannot be labeled as a causative factor because it could possibly just be a marker for other unrecognized factors (10).
 * STATISTICALLY SIGNIFICANT

__** Limitations **__ → The biggest limitation of the particular study that we have covered in this intraoperative section is that the patients that were included in the study were all undergoing elective surgeries. Therefore the outcomes may not be generalized to other, older patients undergoing emergency surgeries (10).


 * __ Summary: __** The intraoperative risk factors discussed above are the most commonly researched factors in developing postoperative delirium. Route of anesthesia, intraoperative hypotension, and bradycardia/tachycardia are **not** considered statistically significant in the development of delirium. Whereas, blood loss, number of blood transfusions, and the lowest postoperative hematocrit level were associated with delirium. As far as preventative measures, these are all possible risk factors when having surgery, so there really is no way to prevent them (more transfusions to keep hematocrit level above 30%). Although we cannot take steps as a PT to help prevent these factors, what can be taken away from this section is knowing when someone might be at a higher risk for developing postoperative delirium based on what happens during their surgery.

Clinical Application- the “So what?” Aside from the negative effects delirium has on the patient, their caregivers, and the health professionals that treat them, it can also lead to postoperative complications. These complications lead to poor cognitive and functional recovery, greater length of stay, and cost to the patient. Having postoperative delirium (especially in elderly patients) can cause a waterfall of adverse effects that lead to a serious decline in functionality and ultimately the patient's independence ( 10 ).

PT intervention is very limited when it comes to post-op delirium, but by performing pre-operative interventions in order to reduce the risk of post-op delirium, potentially more patients can perform their inpatient rehab faster and be out of the hospital quicker, reducing hospital length of stay and improving the quality of care patients receive. In a study in 2014 that looked at preoperative physical therapy for total joint replacement. When patients were given preoperative PT there was a 29% reduction in postoperative cost including reduction in skilled nursing and inpatient rehab billing ( 14 ).


 * Our CPR for postoperative delirium?? **
 * Preoperative Cognition
 * Advanced Age
 * Nutrition
 * Hemodynamic Complications (Blood loss / Lowest Postoperative Hematocrit Levels)


 * References **
 * 1) Chen, W., Ke, X., Wang, X., Sun, X., Wang, J., Yang, G., ... & Zhang, L. (2017). Prevalence and risk factors for postoperative delirium in total joint arthroplasty patients: A prospective study. General Hospital Psychiatry.
 * 2) Chu, C. S., Liang, C. K., Chou, M. Y., Lin, Y. T., Hsu, C. J., Chou, P. H., & Chu, C. L. (2016). Short-Form Mini Nutritional Assessment as a useful method of predicting the development of postoperative delirium in elderly patients undergoing orthopedic surgery. General hospital psychiatry, 38, 15-20.
 * 3) Ely, E. W., Inouye, S. K., Bernard, G. R., Gordon, S., Francis, J., May, L., ... & Hart, R. P. (2001). Delirium in mechanically ventilated patients: validity and reliability of the confusion assessment method for the intensive care unit (CAM-ICU). Jama, 286(21), 2703-2710.
 * 4) Douglas, V. C., Hessler, C. S., Dhaliwal, G., Betjemann, J. P., Fukuda, K. A., Alameddine, L. R., ... & Josephson, S. A. (2013). The AWOL tool: derivation and validation of a delirium prediction rule. Journal of hospital medicine, 8(9), 493-499.
 * 5) Fisher, B. W., & Flowerdew, G. (1995). A simple model for predicting postoperative delirium in older patients undergoing elective orthopedic surgery. Journal of the American Geriatrics Society, 43(2), 175-178.
 * 6) Kappen, T. H., Wesselink, E. M., van Klei, W. A., & Slooter, A. J. C. (2016). Intraoperative hypotension and postoperative delirium: no confusion on confounding. British journal of anaesthesia, 116(6), 887-888.
 * 7) Kalisvaart, K. J., Vreeswijk, R., De Jonghe, J. F., Van Der Ploeg, T., Van Gool, W. A., & Eikelenboom, P. (2006). Risk Factors and Prediction of Postoperative Delirium in Elderly Hip‐Surgery Patients: Implementation and Validation of a Medical Risk Factor Model. Journal of the American Geriatrics Society, 54(5), 817-822.
 * 8) Litaker, D., Locala, J., Franco, K., Bronson, D. L., & Tannous, Z. (2001). Preoperative risk factors for postoperative delirium. General hospital psychiatry, 23(2), 84-89.
 * 9) Marcantonio ER, Goldman L, Mangione CM, Ludwig LE, Muraca B, Haslauer CM, Donaldson MC, Whittemore AD, Sugarbaker DJ, Poss R, Haas S, Cook EF, Orav EJ, Lee TH. A Clinical Prediction Rule for Delirium After Elective Noncardiac Surgery. JAMA. 1994;271(2):134-139. doi:10.1001/jama.1994.03510260066030
 * 10) Marcantonio, E. R., Goldman, L., Orav, E. J., Cook, E. F., & Lee, T. H. (1998). The association of intraoperative factors with the development of postoperative delirium. The American journal of medicine, 105(5), 380-384.
 * 11) Mazzola, P., Ward, L., Zazzetta, S., Broggini, V., Anzuini, A., Valcarcel, B., ... & Annoni, G. (2017). Association Between Preoperative Malnutrition and Postoperative Delirium After Hip Fracture Surgery in Older Adults. Journal of the American Geriatrics Society.
 * 12) Plaschke, K., Von Haken, R., Scholz, M., Engelhardt, R., Brobeil, A., Martin, E., & Weigand, M. A. (2008). Comparison of the confusion assessment method for the intensive care unit (CAM-ICU) with the Intensive Care Delirium Screening Checklist (ICDSC) for delirium in critical care patients gives high agreement rate (s). Intensive care medicine, 34(3), 431-436.
 * 13) Rudolph, J. L., Doherty, K., Kelly, B., Driver, J. A., & Archambault, E. (2016). Validation of a delirium risk assessment using electronic medical record information. Journal of the American Medical Directors Association, 17(3), 244-248.
 * 14) Snow, R., Granata, J., Ruhil, A. V., Vogel, K., McShane, M., & Wasielewski, R. (2014). Associations between preoperative physical therapy and post-acute care utilization patterns and cost in total joint replacement. J Bone Joint Surg Am, 96(19), e165.
 * SM, Edward R. Marcantonio MD. "A Clinical Prediction Rule for Delirium After Elective Noncardiac Surgery." JAMA.
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