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Aging and Delirium: Too Much or Too Little Pain Medication?
Original Articles Aging and Delirium: Too Much or Too Little Pain Medication? yyy Sherry Robinson, PhD, RNCS,* Charlene Vollmer, BSN, RNBC,† Holly Jirka, MSN, RNBC,† Catherine Rich, BSN, RNBC,† Carol Midiri, RNBC,† and Donna Bisby, RNBC†
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From the *SIU School of Medicine, Springfield, Illinois; and †Memorial Medical Center, Springfield, Illinois. Address correspondence to Sherry Robinson, PhD, RNCS, Assistant Professor, Department of Internal Medicine, SIU School of Medicine, P.O. Box 19636, Springfield, Illinois 627949636. E-mail: [email protected]. 1524-9042/$34.00 © 2008 by the American Society for Pain Management Nursing doi:10.1016/j.pmn.2007.12.002
ABSTRACT:
Review of the literature revealed an association of pain and delirium in hip fracture patients. The literature was sparse addressing other types of patients. The purpose of the present study was therefore to examine the association of pain and delirium in medical and surgical patients. A retrospective record review was conducted using records of 100 patients who developed delirium while hospitalized. Data included: age, comorbidities, hospital day when delirium developed, presence of major risk factors for delirium on admission, and amount of medication received in the 24 h before onset of delirium. Descriptive statistics, correlations, and univariate analysis of variance were used to determine association between the variables. The mean age was 76.71 years. The mean number of comorbities was 2.22. The mean number of risk factors for delirium on admission was 2.26 (range 0 to 5). The mean percentage of total amount of medication ordered that was received was 27.67%. Those individuals admitted with a risk factor of hearing loss received significantly less amount of pain medication than those with other risk factors (p ⴝ .023). Nurses should carefully assess pain management in their older patients. If using a PCA pump, the older patient’s ability to manage the pump should be reassessed often. If a patient is admitted with risk factors for development of delirium, unmanaged pain might be the additional factor that precipitates delirium. © 2008 by the American Society for Pain Management Nursing
Delirium, also known as acute confusion, is common in hospitalized elders and can result in poor outcomes. Delirium occurs in as many as 50% of general hospital patients and rises to more than 80% in intensive care patients and patients at the end of life (Esper & Heidrich, 2005; Inouye, 1998; Inouye, 2006; Pisani, McNicoll, & Inouye, 2003). Delirium is associated with increased morbidity, increased length of stay, poorer functional outcomes, increased risk of nursing home placement, and increased patient care costs (Pompei, Foreman, Rudberg, Inouye, Braund & Cassel, 1994). Medicare hospital expenditures attributable to delirium are nearly $6.9 billion (Inouye, 2006). The clinical Pain Management Nursing, Vol 9, No 2 (June), 2008: pp 66-72
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features include a rapid onset, disordered attention, disturbance of the sleep-wake cycle, and a fluctuating course with deterioration in the evening. Alertness can be either increased (hyperactive) or decreased (hypoactive) (Burns, Gallagley, & Byrne, 2004). Many studies have identified potential causative factors; however, most causes of delirium appear to be multifactorial. Two to six factors may be present in any case. Often, patients are admitted to the hospital with predisposing factors to delirium, including: older age; diagnosis of dementia, depression, or alcoholism; vision or hearing loss; history of mental status changes; mobility impairment; and dehydration. Then something in the hospital triggers the onset of delirium. These precipitating factors are hospital- or treatmentrelated factors that further contribute to the development of delirium. Precipitating factors that have been identified are physical restraints, malnutrition, more than three medications added, use of a bladder catheter, and any iatrogenic event. Those who have predisposing factors can easily develop delirium when a precipitating factor is added (Burns et al., 2004; Inouye & Charpentier, 1996; Inouye, Viscoli, Horwitz, Hurst, & Tinetti, 1993; Meagher, 2001). There is evidence from carefully controlled laboratory studies that pain can impact cognition and thus might precipitate delirium. Pain demands attention and generally interrupts ongoing thought processes. Crombez, Eccleston, Baeyens, & Eelen (1996) were able to elicit changes in cognition in a study of 26 young adults who were subjected to a painful stimulus and then given tests of attention and reaction time. They found that subjects reported being distracted by the pain stimulus. Both reaction time and attention span deteriorated in the subjects. In a follow-up study, these same researchers were able to demonstrate that pain interrupts and distracts. Subjects had difficulty disengaging from the pain to complete tasks (Crombez, Eccleston, Baeyens, & Eelen, 1997). Similarly, Eccleston (1995) demonstrated in a laboratory setting that subjects experiencing high-intensity pain could not maintain attention to a task as well as subjects with low-intensity pain. In a study of subjects with chronic pain, Karp et al. (2006) found that pain severity was associated with increased impairment on the Trails Number-Letter Switching Test, which tests mental flexibility. Findings from these laboratory studies indicate that unmanaged pain, both acute and chronic, can affect mental status and might precipitate delirium. Studies of the relationship of pain and delirium have been conducted with surgical patients, primarily hip fracture patients. In a large prospective cohort study of 541 hip fracture patients, 16% became delirious. Severe pain was associated with a ninefold risk of
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developing delirium (Morrison et al., 2003). In several studies, researchers hypothesized that opioid analgesics precipitated delirium. In a study by Schuurmans, Duursma, Shortridge-Baggett, Clevers, & Pel-Little (2003), 19.6% of 92 subjects with hip fracture developed delirium. Data were collected on a number of potential precipitating factors, including use of morphine. Presence or absence of use of morphine was recorded and the association between morphine and delirium determined. The use of morphine for pain control was not associated with the development of delirium. Brauer, Morrison, Silberzweig, & Liu (2000) found that in a group of 54 patients with hip fracture who developed delirium, only one case could definitely be attributed to opioids. Neither study reported amounts of pain medication received. Because delirium onset may be related to the dose of analgesia, analysis of the dose in relation to onset of delirium would have been helpful. Rao and Cherukuri (2006) concluded that opioid analgesia, given in appropriate doses, does not increase the risk of delirium for patients with hip fracture and that inadequate postoperative pain control increases the risk of delirium. Several studies suggest that when pain is managed in hip-fracture patients, delirium is lessened (Marcantonio, Flacker, Wright, & Resnick, 2001; Milisen et al., 2001). In a randomized study of patients undergoing surgery after hip fracture, researchers found that the implementation of nine specific interventions, which included pain management, statistically reduced delirium by one-third. Pain management consisted of: 1) around-the-clock acetaminophen (1 g four times daily); 2) low-dose subcutaneous morphine early in the postoperative period; and 3) oxycodone later in the postoperative period (Marcantonio et al., 2001). In another study of hip fracture patients, a nurse-led interdisciplinary intervention program for delirium was implemented in the experimental group, and the control group received usual care. The patients in the experimental group received a scheduled pain protocol of a short-acting weak opioid in combination with a nonopioid analgesic (acetaminophen). Although there was no significant difference in the incidence of delirium in the two groups, the duration of delirium was much shorter in the experimental group. Delirium lasted a mean of 1 day compared with 4 days in the control group. Additionally, the severity of delirium as measured by the Confusion Assessment Method was much less in the intervention group (Milisen et al., 2001). Literature is sparse on the relationship between pain and delirium in types of patients other than hip fracture. Agnoletti et al. (2005) studied a variety of surgical patients and determined that delirium typi-
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cally presents early in the postoperative period. Lynch, Lazor, Gellis, Orav, Goldman, & Marcantonio (1998) noted that patients were at highest risk for delirium during the first three postoperative days, and peak incidence occurred on postoperative day 2. After controlling for preoperative risk factors for delirium, higher pain scores at rest were significantly associated with the development of delirium. The authors explained that uncontrolled pain might affect sleep-wake cycle and hormonal levels, thus causing delirium. More recently, Vaurio, Sands, Wang, Mullen, & Leung (2006) prospectively followed 333 patients with a mean age of 74 years for 3 days after major noncardiac surgery. Forty-six percent developed delirium. Preoperative resting pain and increase in pain from baseline to postoperative day 1 were significantly associated with delirium. Pain is a readily treatable symptom; however, it is relatively unrecognized as a potential precipitating factor for delirium (Burns et al., 2004). The relationship of pain and delirium has been studied in patients recovering from hip fracture, but rarely in other groups particularly medical patients. The purpose of the present study was to examine the characteristics of both medical and surgical patients who developed delirium during hospitalization in relation to pain management. Particular attention was given to the amount of medication received in the 24 h before the onset of delirium.
METHODS Design This descriptive study was conducted in a 500-bed midwestern U.S. hospital. Data were collected using retrospective review of the records of 100 patients who developed delirium during hospitalization. Inclusion criteria were patients with: 1) a diagnosis that typically has associated pain, acute or chronic; 2) pain medication ordered; 3) documentation of normal orientation on admission (knows name, date, place, and situation); and 4) discharge diagnosis of delirium. Patients were excluded if they had an admission diagnosis of delirium or dementia. Data Collection Demographic data retrieved from the chart included age, gender, primary diagnosis, and Charlson Comorbidity Score (Charlson, Pompei, Ales, & MacKenzie, 1987). Each record was reviewed for the presence of major risk factors for delirium present on admission (vision impairment, hearing impairment, history of cognitive impairment, sleep deprivation, immobility, and dehydration [blood urea nitrogen/creatinine ratio
ⱖ18]) (Inouye et al., 1993). The number of days after admission and the time of day when signs and symptoms were first documented were recorded. Based on the signs and symptoms recorded in the nurses’ notes, the data collectors classified the delirium as hypoactive, hyperactive, or mixed. Classification of delirium was of interest because it was expected that clinicians might not recognize the hypoactive form of delirium. Data on pain management were recorded, including: name of drug; dosage; PRN, scheduled, or PCA administration; and number of doses and total milligrams received in the 24 h before onset of delirium. The physician progress notes were reviewed to identify the physician’s opinion of the probable cause of delirium. Patient outcomes were retrieved, including whether the delirium cleared by discharge, whether the patient died, and whether the patient was readmitted within 2 weeks. Analysis Means, percentages, and frequencies were determined for variables as appropriate. The actual amount of pain medication received during the 24 h before the onset of delirium was divided by the amount the patient could have received according to the order to determine the outcome of “percentage of allowed pain medication received.” Correlations were determined for the variables of age, medical or surgical diagnoses, comorbidities, admission risk factors, number of days after admission or surgery when delirium was first noted, and percentage of allowed pain medication received. Univariate analysis of variance was used to determine association between variables and percentage of total allowed pain medication received.
RESULTS The mean age of the 100 patients who developed delirium was 76.71 years (range 41-90 years), with 62 men and 38 women. The mean number of comorbidities was 2.22 (range 0-9). Forty-two of the patients had a medical diagnosis causing pain, and 58 patients had pain as a result of surgery. The most common surgical diagnoses were abdominal surgery and hip fracture. The most common medical diagnoses were back pain and arthritis. The mean number of risk factors for delirium on admission was 2.26 (range 0-5); vision impairment was the most common, with 82 patients having some form of vision impairment. Regarding the other risk factors, 39 patients had hearing impairment, 39 had impaired mobility, 34 were dehydrated, and 26 experienced sleep problems. Forty-six cases of delirium were first noted on the night shift, 31 cases on the evening shift, and 23 cases
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Pain Medication and Delirium
TABLE 1. Percentage of Allowed Pain Medication Actually Received in Patients Who Developed Delirium
Medication
Administration
Number of Patients Who Received the Drug
Morphine Morphine Vicodin (hydrocodone/acetaminophen) Tylenol (acetaminophen) Darvocet-N (propoxyphene-N/acetaminopohen) Tylenol #3 (acetaminophen/codeine) Duragesic (fentanyl transdermal) Dilaudid (hydromorhone) Ultracet (tramadol/acetaminophen) Ultram (tramadol) Demerol (meperidine)
PCA PRN PRN PRN PRN PRN Scheduled PCA PRN PRN PRN
41 13 13 11 8 5 5 1 1 1 1
on the day shift. The most common symptom recorded in the record was disorientation, followed by inattention. Forty cases were classified as hypoactive, 54 hyperactive, and 6 mixed. Table 1 shows the name of the pain medication given, how often administered, and the mean percentage received of the total amount of pain medication the patient could have received during the 24 h before the onset of delirium. The mean for all patients was 27.67%. Further examination of morphine usage was conducted by using the work of Macintyre and Jarvis (1996), who suggested that expected 24-h morphine requirement declines with age and can be estimated by the formula: mg ⫽ 100 ⫺ age. This estimated morphine requirement was computed for each patient that was receiving morphine. The milligrams of morphine received in the 24 h before onset of delirium was then divided by the estimated morphine requirement. The percentage of the expected amount was still low, at 37%. Before discharge, mental status had improved in 61 patients. Five patients died, and 18 patients were readmitted within 2 weeks. In the progress notes, 39 cases of delirium were attributed to pain management and 36 were specifically attributed to opioid analgesics. The opioids were stopped, even though there was no evidence that anyone had considered how much opioid was received. In only three cases did the physician consider that the delirium might be related to lack of pain control. The remaining suspected causes of delirium were as follows: 11 were multifactorial, 4 were ICU psychosis, 3 were metabolic, and those of 2 general medical patients were labeled as environmental. There was a significant mild correlation between the number of days after admission or surgery that
Mean % Received of Total Amount That Could Have Been Received 12.00% 30.67% 41.62% 19.42% 22.88% 26.00% 100.00% 97.00% 25.00% 17.00% 13.00%
delirium occurred and percentage of total pain medication patient received (r ⫽ 0.269; p ⫽ .007). The onset of delirium was later in patients who received greater amounts of pain medication. Age and number of admission risk factors were moderately correlated (r ⫽ .413; p ⬍ .001). Using analysis of variance with percentage of pain medication as the dependent variable, there was a significant difference in one admission risk factor, hearing impairment (p ⫽ .023). Individuals with hearing impairment received the lowest amount of pain medication.
DISCUSSION AND NURSING IMPLICATIONS The demographic findings from the study were similar to previous studies of delirium. Not surprisingly, these 100 patients who developed delirium were older adults. Most researchers have found that elders are at greater risk (Brauer et al., 2000; Burns et al., 2004). Almost twice as many men as women experienced delirium. Except in studies of hip fracture patients, where 80% of the patients were women, male gender has been listed by researchers as a predisposing factor in delirium. The presence of coexisting medical conditions is also a predisposing factor. In the present study, the comorbidity index for these patients was 2.2 (Brauer et al., 2000; Burns et al., 2004; Inouye, 2006). Twice as many cases of delirium were noted on the night shift as on the day shift. Whether or not the symptoms first occurred on the night shift is unknown, but the night shift was when the symptoms were recognized by the nurses. The majority of the cases were classified as hyperactive, which is typical.
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Many nurses define delirium in terms of agitated behavior and fail to recognize the hypoactive version. The sample was nearly equally divided between medical and surgical patients. The most common diagnoses in the medical patients were arthritis and back pain. It could be inferred that much of the pain in the medical group may have been chronic pain, lending support that unmanaged chronic pain as well as acute pain may be implicated in the precipitation of delirium. The most profound finding was the small amount of pain medication received during the 24 h before onset of delirium. We compared the amount received against the amount the patient could have received according to the physician order. Even when the amount received was compared with the expected amount to be used based on age, the patients who developed delirium were still undermedicated. The study finding of low amounts of PCA medication is of interest. This may be related to several factors, including higher efficacy of intravenous drug administration, difficulty in use of the pump by the elderly, or cultural and generational bias of some elders toward stoicism (Grass, 2005). Some older patients are fearful of using too much pain medication and may endure pain needlessly (Everett & Salamonson, 2005). Geriatric patients should be assessed preoperatively and immediately postoperatively to ensure that they can manage the pump both physically and cognitively. Learning to use the PCA concept requires sufficient preoperative mental status. Yet, not all surgeries are planned so that patients have the opportunity to learn PCA before surgery. Keita et al. (2003) suggested that older patients be given the Mini Mental State Exam (MMSE) before surgery. Those researchers also found that in a group of 40 patients aged over 70 years undergoing total hip replacement, the MMSE declined significantly 2 h after surgery and remained at that lower level for 48 h. This is a critical period of time. If the older patient cannot cognitively manage the PCA pump, pain may get out of control. This is supported by the experimental work of Crombez et al. (1996), 1997), who determined that pain interferes with task performance. If a patient is in severe pain, there will be cognitive interference, and the patient may not be able to complete the task of pushing the button on the PCA pump. Thus, the older patient’s ability to use the pump should be assessed frequently. It may be that neither PCA nor PRN medication is appropriate for older adults. Asher (2004) recommended that postsurgical pain medication be scheduled for older adults. Vaurio et al. (2006) found that older patients who used oral opioid analgesics on a
scheduled basis were at decreased risk of developing delirium compared with those who used intravenous PCA management of pain. The same is true with older medical patients who are in pain. They, too, should be assessed frequently for their ability to use the pump. A variety of medical and treatment-related factors could impinge on their mental status and affect their ability to use a PCA pump. Scheduled dosing of pain medication around the clock may be a better method of managing pain in hospitalized older patients. Review of the physician progress notes indicated that many of the cases of delirium were readily attributed to opioids. It was apparent that the amount of opioid the patient had received was not determined before discontinuation. Evidence demonstrates that most opioids do not cause cognitive changes. In the study by Lynch et al. (1998), cumulative opioid doses were not associated with an increased risk of delirium. Ersek, Cherrier, Overman, & Irving (2004) reviewed the empiric literature regarding the cognitive effects of opioids. From their systematic review of the literature, those authors concluded that the evidence reveals minimal to no significant cognitive changes associated with opioids. In a systematic review of postoperative patients by Fong, Sands, & Leung (2006), only meperidine was associated with increased delirium. There were no convincing data to indicate that morphine, fentanyl, or hydromorphone increased the risk of delirium. Similarly, in hip fracture patients, Morrison et al. (2003) demonstrated that opioids, with the exception of meperidine, do not precipitate delirium in patients with hip fracture. Although patients in earlier studies reported sedation and mental dullness, there were no marked deficits in cognition as measured by validated neuropsychiatric instruments. Many doctors and nurses believe that opioids should be used sparingly. They immediately assume that opioids are the culprit when elders experience delirium. More education is needed for all health care providers to destroy this myth and clarify the issue. Esper and Heidrich (2005) stressed the importance of evaluating all potential causes of delirium rather than quickly blaming the opioid as the causative factor. If the clinician rules out other factors, then it would be appropriate to change to an equianalgesic dose of another opioid rather than stopping all opioids. Eight of the patients received propoxyphene-N, and one received meperidine. There is a considerable amount of literature that links these drugs to delirium in elders (Fong, Sands, & Leung, 2006; Morrison, 2003). In their guidelines on pain management, the American Geriatrics Society (AGS) discourages the use of both medications with elders. Propoxyphene’s effi-
Pain Medication and Delirium
cacy is similar to acetaminophen alone, but because of drug accumulation it can have neuroexcitatory effects (AGS Panel on Persistent Pain in Older Persons, 2002). Propoxyphene or meperidine may have contributed to the delirium in these patients. Another serious finding of the present study was that patients with the predisposing risk factor of hearing impairment received the lowest amount of pain medication. This may reflect a communication issue. It may be that the older patient with a hearing impairment is not hearing how to use a PCA pump if ordered. He or she may not hear explanations from nurses on how to ask for PRN pain medication or may misunderstand the nurses when they ask about pain symptoms. This finding stresses the importance of using proper techniques in communicating with older patients with hearing losses or improving communication with devices such as pocket-talkers.
LIMITATIONS AND FUTURE RESEARCH One of the difficulties in conducting this study was related to retrieving charts where the physician had identified delirium as a diagnosis. Because this was a retrospective study, the study was totally dependent on clinician recognition and documentation of delirium. Delirium was rarely included in the discharge summaries. This problem in itself supports findings from the literature that delirium is often unrecognized in the hospital setting. This is partly due to lack of clinicians’ use of valid and reliable instruments to assess delirium. This may also be related to clinicians’ failure to appreciate the consequences of delirium. Underdiagnosis can lead to serious outcomes, such as complications, prolonged hospital stay, and even death. Routine use of a simple instrument, such as the Confusion Assessment Method or the Nursing Delirium Screening Scale, could improve recognition of delirium and reduce the associated morbidity and mortality (Gaudreau, Gagnon, Harel, Tremblay, & Roy,
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2005; Inouye, 2006; Inouye, Van Dyck, Alessi, Balkin, Siegal, & Horwitz, 1990). In hindsight, the study could have been improved if attention was given to pain intensity rating and appropriateness of medications prescribed. Additional insight would have been provided regarding adequate pain management. The design of the study is limited in that it is a retrospective record review, which is dependent on accurate documentation. Another limitation is lack of a comparison group. The outcomes of the study would be strengthened by comparing this group of patients with a matched group of patients who did not develop delirium. More information about the influence of lack of pain control and the development of delirium could be obtained. Another suggestion for future research would be to examine the appropriateness of use of the PCA pump for the geriatric patient. Many elders might do quite well, but others may experience difficulty. Unmanaged pain may contribute to cognitive impairment, and cognitive impairment may impact elders’ ability to use the PCA pump. A vicious cycle may ensue that could be interrupted by careful assessment. In conclusion, this was a descriptive study, and no association between delirium and pain can be determined from this design. The study did reveal that patients with pain who developed delirium had received only a fraction of the ordered pain medication during the 24 h before the onset of delirium. This provides a hint that there may be a relationship between inadequate pain management and development of delirium in medical patients with chronic pain as well as surgical patients with acute pain. Although the cause of delirium is multifactorial in most patients, it behooves all nurses to focus on adequate pain management in their elderly patients. If the patient is admitted with risk factors for development of delirium, unmanaged pain might be the additional factor that precipitates delirium.
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Asher, M. E. (2004). Surgical considerations in the elderly. Journal of PeriAnesthesia Nursing, 19(6), 406414. Brauer, C., Morrison, R. S., Silberzweig, S. B., & Siu, A. L. (2000). The cause of delirium in patients with hip fracture. Archives of Internal Medicine, 160, 1856-1860. Burns, A., Gallagley, A., & Byrne, J. (2004). Delirium. Journal of Neurology, Neurosurgery, & Psychiatry, 75, 362-367.
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Charlson, M. E., Pompei, P., Ales, K. L., & MacKenzie, C. R. (1987). A new method of classifying prognostic comorbidity in longitudinal studies: development and validation. Journal of Chronic Diseases, 40(5), 373-383. Crombez, G., Eccleston, C., Baeyens, F., & Eelen, P. (1996). The disruptive nature of pain: an experimental investigation. Behavioral Research & Therapy, 34(11/12), 911-918. Crombez, G., Eccleston, C., Baeyens, F., & Eelen, P. (1997). Habituation and the interference of pain with task performance. Pain, 70, 149-154. Eccleston, C. (1995). Chronic pain and distraction: an experimental investigation into the role of sustained and shifting attention in the processing of chronic persistent pain. Behavioral Research and Therapy, 33(4), 39914405. Ersek, M., Cherrier, M. M., Overman, S. S., & Irving, G. A. (2004). The cognitive effects of opioids. Pain Management Nursing, 5 (2), 75-93. Esper, P., & Heidrich, D. (2005). Symptom clusters in advanced illness. Seminars in Oncology Nursing, 21(1), 20-28. Everett, B., & Salamonson, Y. (2005). Differences in postoperative opioid consumption in patients prescribed patient-controlled analgesia versus intramuscular injection. Pain Management Nursing, 6 (4), 137-144. Fong, H. K., Sands, L. P., & Leung, J. M. (2006). The role of postoperative analgesia in delirium and cognitive decline in elderly patients: a systematic review. Anesthesia & Analgesia, 102, 1255-1266. Grass, J. A. (2005). Patient-controlled analgesia. Anesthesiology & Analgesia, 101, S44-S61. Gaudreau, J., Gagnon, P., Harel, F., Tremblay, A., & Roy, M. (2005). Fast, systematic, and continuous delirium assessment in hospitalized patients; the nursing delirium screening scale. Journal of Pain and Symptom Management, 29(4), 368-375. Inouye, S. K. (1998). Delirium in hospitalized older patients. Clinics in Geriatric Medicine, 14, 745-68. Inouye, S. K. (2006). Delirium in older persons. The New England Journal of Medicine, 354, 1157-65. Inouye, S. K., & Charpentier, P. A. (1996). Precipitating factors for delirium in hospitalized elderly persons: a predictive model and interrelationship with baseline vulnerability. Journal of the American Medical Association, 275, 852-857. Inouye.S. K., van Dyck, C. H., Alessi, C. A., Balkin, S., Siegal, A. P., & Horwitz, R. I.. (1990). Clarifying confusion: The confusion assessment method: a new method for detection of delirium. Annals of Internal Medicine, 113, 941-948. Inouye S. K., Viscoli, C. M., Horwitz, R. I., Hurst, L. D., & Tinetti, M. E. (1993). A predictive model for delirium in hospitalized elderly medical patients based on admission characteristics. Annals of Internal Medicine, 119, 474-480.
Karp, J. F., Reynolds, C. F., Butters, M. A., Dew, M. A., Mazumdar, S., Begley, A. E., Lenze, E., & Weiner, D. K. (2006). The relationship between pain and mental flexibility in older adult pain clinic patients. Pain Medicine, 7(5), 444-452. Keita, H., Geachan, N., Dahmani, S., Couderc, E., Armand, C., Quazza, M., Mantz, J., & Desmonts, J. M. (2003). Comparison between patient-controlled analgesia and subcutaneous morphine in elderly patients after total hip replacement. British Journal of Anaesthesia, 90(1), 53-57. Lynch, E. P., Lazor, M. A., Gellis, J. E., Orav, J., Goldman, L., & Marcantonio, E. R. (1998). The impact of postoperative pain on the development of postoperative delirium. Anesthesia & Analgesia, 86, 781-785. Macintyre P. E. & Jarvis, D. A. (1996). Age is the best predictor of postoperative morphine requirements. Pain, 64, 357-64. Marcantonio, E. R., Flacker, J. M., Wright, R. J., & Resnick, N. M. (2001). Reducing delirium after hip fracture: a randomized trial. Journal of the American Geriatrics Society, 49, 516-522. Meagher, D. M. (2001). Delirium: optimizing management. British Medical Journal, 322, 144-149. Milisen, K., Foreman, MD, Abraham, I. L., De Geest, S., Godderis, J., Vandermeulen, E., Fischler, B.., Delooz, H. H., Spiessens, B., & Broos, P. L.. (2001). A nurse-led interdisciplinary intervention program for delirium in elderly hipfracture patients. Journal of the American Geriatrics Society, 49, 523-532. Morrison, R. S., Magaziner, J., Gilbert, M., Koval, K. J., McLaughlin, M. A., Orosz, G., Strauss, E., & Siu, A. L. (2003). Relationship between pain and opioid analgesics on the development of delirium following hip fracture. Journal of Gerontology: Medical Sciences, 58A, 58A, 7681. Pisani, M. A., McNicoll, L., & Inouye, S. K. (2003). Cognitive impairment in the intensive care unit. Clinics of Chest Medicine, 24, 727-37. Pompei, P., Foreman, M., Rudberg, M., Inouye, S., Braund, V., & Cassel, C. (1994). Delirium in hospitalized older person: outcomes and predictors. Journal of the American Geriatric Society, 42,809-815. Rao, S. S., & Cherukuri, M. (2006). Management of hip fracture: The family physician’s role. American Academy of Family Physicians, 73(12), 2195-2200. Schuurmans, M. J., Duursma, S. A., Shortridge-Baggett, L. M., Clevers, G. & Pel-Little, R. (2003). Elderly patients with a hip fracture: the risk of delirium. Applied Nursing Research, 16(2), 75-84. Vaurio, L. E., Sands, L. P., Wang, Y., Mullen, E. A., & Leung, J. M.. (2006). Postoperativedelirium: the importance of pain and pain management. Anesthesia & Analgesia, 102, 1267-73.
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From the *SIU School of Medicine, Springfield, Illinois; and †Memorial Medical Center, Springfield, Illinois. Address correspondence to Sherry Robinson, PhD, RNCS, Assistant Professor, Department of Internal Medicine, SIU School of Medicine, P.O. Box 19636, Springfield, Illinois 627949636. E-mail: [email protected]. 1524-9042/$34.00 © 2008 by the American Society for Pain Management Nursing doi:10.1016/j.pmn.2007.12.002
ABSTRACT:
Review of the literature revealed an association of pain and delirium in hip fracture patients. The literature was sparse addressing other types of patients. The purpose of the present study was therefore to examine the association of pain and delirium in medical and surgical patients. A retrospective record review was conducted using records of 100 patients who developed delirium while hospitalized. Data included: age, comorbidities, hospital day when delirium developed, presence of major risk factors for delirium on admission, and amount of medication received in the 24 h before onset of delirium. Descriptive statistics, correlations, and univariate analysis of variance were used to determine association between the variables. The mean age was 76.71 years. The mean number of comorbities was 2.22. The mean number of risk factors for delirium on admission was 2.26 (range 0 to 5). The mean percentage of total amount of medication ordered that was received was 27.67%. Those individuals admitted with a risk factor of hearing loss received significantly less amount of pain medication than those with other risk factors (p ⴝ .023). Nurses should carefully assess pain management in their older patients. If using a PCA pump, the older patient’s ability to manage the pump should be reassessed often. If a patient is admitted with risk factors for development of delirium, unmanaged pain might be the additional factor that precipitates delirium. © 2008 by the American Society for Pain Management Nursing
Delirium, also known as acute confusion, is common in hospitalized elders and can result in poor outcomes. Delirium occurs in as many as 50% of general hospital patients and rises to more than 80% in intensive care patients and patients at the end of life (Esper & Heidrich, 2005; Inouye, 1998; Inouye, 2006; Pisani, McNicoll, & Inouye, 2003). Delirium is associated with increased morbidity, increased length of stay, poorer functional outcomes, increased risk of nursing home placement, and increased patient care costs (Pompei, Foreman, Rudberg, Inouye, Braund & Cassel, 1994). Medicare hospital expenditures attributable to delirium are nearly $6.9 billion (Inouye, 2006). The clinical Pain Management Nursing, Vol 9, No 2 (June), 2008: pp 66-72
Pain Medication and Delirium
features include a rapid onset, disordered attention, disturbance of the sleep-wake cycle, and a fluctuating course with deterioration in the evening. Alertness can be either increased (hyperactive) or decreased (hypoactive) (Burns, Gallagley, & Byrne, 2004). Many studies have identified potential causative factors; however, most causes of delirium appear to be multifactorial. Two to six factors may be present in any case. Often, patients are admitted to the hospital with predisposing factors to delirium, including: older age; diagnosis of dementia, depression, or alcoholism; vision or hearing loss; history of mental status changes; mobility impairment; and dehydration. Then something in the hospital triggers the onset of delirium. These precipitating factors are hospital- or treatmentrelated factors that further contribute to the development of delirium. Precipitating factors that have been identified are physical restraints, malnutrition, more than three medications added, use of a bladder catheter, and any iatrogenic event. Those who have predisposing factors can easily develop delirium when a precipitating factor is added (Burns et al., 2004; Inouye & Charpentier, 1996; Inouye, Viscoli, Horwitz, Hurst, & Tinetti, 1993; Meagher, 2001). There is evidence from carefully controlled laboratory studies that pain can impact cognition and thus might precipitate delirium. Pain demands attention and generally interrupts ongoing thought processes. Crombez, Eccleston, Baeyens, & Eelen (1996) were able to elicit changes in cognition in a study of 26 young adults who were subjected to a painful stimulus and then given tests of attention and reaction time. They found that subjects reported being distracted by the pain stimulus. Both reaction time and attention span deteriorated in the subjects. In a follow-up study, these same researchers were able to demonstrate that pain interrupts and distracts. Subjects had difficulty disengaging from the pain to complete tasks (Crombez, Eccleston, Baeyens, & Eelen, 1997). Similarly, Eccleston (1995) demonstrated in a laboratory setting that subjects experiencing high-intensity pain could not maintain attention to a task as well as subjects with low-intensity pain. In a study of subjects with chronic pain, Karp et al. (2006) found that pain severity was associated with increased impairment on the Trails Number-Letter Switching Test, which tests mental flexibility. Findings from these laboratory studies indicate that unmanaged pain, both acute and chronic, can affect mental status and might precipitate delirium. Studies of the relationship of pain and delirium have been conducted with surgical patients, primarily hip fracture patients. In a large prospective cohort study of 541 hip fracture patients, 16% became delirious. Severe pain was associated with a ninefold risk of
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developing delirium (Morrison et al., 2003). In several studies, researchers hypothesized that opioid analgesics precipitated delirium. In a study by Schuurmans, Duursma, Shortridge-Baggett, Clevers, & Pel-Little (2003), 19.6% of 92 subjects with hip fracture developed delirium. Data were collected on a number of potential precipitating factors, including use of morphine. Presence or absence of use of morphine was recorded and the association between morphine and delirium determined. The use of morphine for pain control was not associated with the development of delirium. Brauer, Morrison, Silberzweig, & Liu (2000) found that in a group of 54 patients with hip fracture who developed delirium, only one case could definitely be attributed to opioids. Neither study reported amounts of pain medication received. Because delirium onset may be related to the dose of analgesia, analysis of the dose in relation to onset of delirium would have been helpful. Rao and Cherukuri (2006) concluded that opioid analgesia, given in appropriate doses, does not increase the risk of delirium for patients with hip fracture and that inadequate postoperative pain control increases the risk of delirium. Several studies suggest that when pain is managed in hip-fracture patients, delirium is lessened (Marcantonio, Flacker, Wright, & Resnick, 2001; Milisen et al., 2001). In a randomized study of patients undergoing surgery after hip fracture, researchers found that the implementation of nine specific interventions, which included pain management, statistically reduced delirium by one-third. Pain management consisted of: 1) around-the-clock acetaminophen (1 g four times daily); 2) low-dose subcutaneous morphine early in the postoperative period; and 3) oxycodone later in the postoperative period (Marcantonio et al., 2001). In another study of hip fracture patients, a nurse-led interdisciplinary intervention program for delirium was implemented in the experimental group, and the control group received usual care. The patients in the experimental group received a scheduled pain protocol of a short-acting weak opioid in combination with a nonopioid analgesic (acetaminophen). Although there was no significant difference in the incidence of delirium in the two groups, the duration of delirium was much shorter in the experimental group. Delirium lasted a mean of 1 day compared with 4 days in the control group. Additionally, the severity of delirium as measured by the Confusion Assessment Method was much less in the intervention group (Milisen et al., 2001). Literature is sparse on the relationship between pain and delirium in types of patients other than hip fracture. Agnoletti et al. (2005) studied a variety of surgical patients and determined that delirium typi-
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cally presents early in the postoperative period. Lynch, Lazor, Gellis, Orav, Goldman, & Marcantonio (1998) noted that patients were at highest risk for delirium during the first three postoperative days, and peak incidence occurred on postoperative day 2. After controlling for preoperative risk factors for delirium, higher pain scores at rest were significantly associated with the development of delirium. The authors explained that uncontrolled pain might affect sleep-wake cycle and hormonal levels, thus causing delirium. More recently, Vaurio, Sands, Wang, Mullen, & Leung (2006) prospectively followed 333 patients with a mean age of 74 years for 3 days after major noncardiac surgery. Forty-six percent developed delirium. Preoperative resting pain and increase in pain from baseline to postoperative day 1 were significantly associated with delirium. Pain is a readily treatable symptom; however, it is relatively unrecognized as a potential precipitating factor for delirium (Burns et al., 2004). The relationship of pain and delirium has been studied in patients recovering from hip fracture, but rarely in other groups particularly medical patients. The purpose of the present study was to examine the characteristics of both medical and surgical patients who developed delirium during hospitalization in relation to pain management. Particular attention was given to the amount of medication received in the 24 h before the onset of delirium.
METHODS Design This descriptive study was conducted in a 500-bed midwestern U.S. hospital. Data were collected using retrospective review of the records of 100 patients who developed delirium during hospitalization. Inclusion criteria were patients with: 1) a diagnosis that typically has associated pain, acute or chronic; 2) pain medication ordered; 3) documentation of normal orientation on admission (knows name, date, place, and situation); and 4) discharge diagnosis of delirium. Patients were excluded if they had an admission diagnosis of delirium or dementia. Data Collection Demographic data retrieved from the chart included age, gender, primary diagnosis, and Charlson Comorbidity Score (Charlson, Pompei, Ales, & MacKenzie, 1987). Each record was reviewed for the presence of major risk factors for delirium present on admission (vision impairment, hearing impairment, history of cognitive impairment, sleep deprivation, immobility, and dehydration [blood urea nitrogen/creatinine ratio
ⱖ18]) (Inouye et al., 1993). The number of days after admission and the time of day when signs and symptoms were first documented were recorded. Based on the signs and symptoms recorded in the nurses’ notes, the data collectors classified the delirium as hypoactive, hyperactive, or mixed. Classification of delirium was of interest because it was expected that clinicians might not recognize the hypoactive form of delirium. Data on pain management were recorded, including: name of drug; dosage; PRN, scheduled, or PCA administration; and number of doses and total milligrams received in the 24 h before onset of delirium. The physician progress notes were reviewed to identify the physician’s opinion of the probable cause of delirium. Patient outcomes were retrieved, including whether the delirium cleared by discharge, whether the patient died, and whether the patient was readmitted within 2 weeks. Analysis Means, percentages, and frequencies were determined for variables as appropriate. The actual amount of pain medication received during the 24 h before the onset of delirium was divided by the amount the patient could have received according to the order to determine the outcome of “percentage of allowed pain medication received.” Correlations were determined for the variables of age, medical or surgical diagnoses, comorbidities, admission risk factors, number of days after admission or surgery when delirium was first noted, and percentage of allowed pain medication received. Univariate analysis of variance was used to determine association between variables and percentage of total allowed pain medication received.
RESULTS The mean age of the 100 patients who developed delirium was 76.71 years (range 41-90 years), with 62 men and 38 women. The mean number of comorbidities was 2.22 (range 0-9). Forty-two of the patients had a medical diagnosis causing pain, and 58 patients had pain as a result of surgery. The most common surgical diagnoses were abdominal surgery and hip fracture. The most common medical diagnoses were back pain and arthritis. The mean number of risk factors for delirium on admission was 2.26 (range 0-5); vision impairment was the most common, with 82 patients having some form of vision impairment. Regarding the other risk factors, 39 patients had hearing impairment, 39 had impaired mobility, 34 were dehydrated, and 26 experienced sleep problems. Forty-six cases of delirium were first noted on the night shift, 31 cases on the evening shift, and 23 cases
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Pain Medication and Delirium
TABLE 1. Percentage of Allowed Pain Medication Actually Received in Patients Who Developed Delirium
Medication
Administration
Number of Patients Who Received the Drug
Morphine Morphine Vicodin (hydrocodone/acetaminophen) Tylenol (acetaminophen) Darvocet-N (propoxyphene-N/acetaminopohen) Tylenol #3 (acetaminophen/codeine) Duragesic (fentanyl transdermal) Dilaudid (hydromorhone) Ultracet (tramadol/acetaminophen) Ultram (tramadol) Demerol (meperidine)
PCA PRN PRN PRN PRN PRN Scheduled PCA PRN PRN PRN
41 13 13 11 8 5 5 1 1 1 1
on the day shift. The most common symptom recorded in the record was disorientation, followed by inattention. Forty cases were classified as hypoactive, 54 hyperactive, and 6 mixed. Table 1 shows the name of the pain medication given, how often administered, and the mean percentage received of the total amount of pain medication the patient could have received during the 24 h before the onset of delirium. The mean for all patients was 27.67%. Further examination of morphine usage was conducted by using the work of Macintyre and Jarvis (1996), who suggested that expected 24-h morphine requirement declines with age and can be estimated by the formula: mg ⫽ 100 ⫺ age. This estimated morphine requirement was computed for each patient that was receiving morphine. The milligrams of morphine received in the 24 h before onset of delirium was then divided by the estimated morphine requirement. The percentage of the expected amount was still low, at 37%. Before discharge, mental status had improved in 61 patients. Five patients died, and 18 patients were readmitted within 2 weeks. In the progress notes, 39 cases of delirium were attributed to pain management and 36 were specifically attributed to opioid analgesics. The opioids were stopped, even though there was no evidence that anyone had considered how much opioid was received. In only three cases did the physician consider that the delirium might be related to lack of pain control. The remaining suspected causes of delirium were as follows: 11 were multifactorial, 4 were ICU psychosis, 3 were metabolic, and those of 2 general medical patients were labeled as environmental. There was a significant mild correlation between the number of days after admission or surgery that
Mean % Received of Total Amount That Could Have Been Received 12.00% 30.67% 41.62% 19.42% 22.88% 26.00% 100.00% 97.00% 25.00% 17.00% 13.00%
delirium occurred and percentage of total pain medication patient received (r ⫽ 0.269; p ⫽ .007). The onset of delirium was later in patients who received greater amounts of pain medication. Age and number of admission risk factors were moderately correlated (r ⫽ .413; p ⬍ .001). Using analysis of variance with percentage of pain medication as the dependent variable, there was a significant difference in one admission risk factor, hearing impairment (p ⫽ .023). Individuals with hearing impairment received the lowest amount of pain medication.
DISCUSSION AND NURSING IMPLICATIONS The demographic findings from the study were similar to previous studies of delirium. Not surprisingly, these 100 patients who developed delirium were older adults. Most researchers have found that elders are at greater risk (Brauer et al., 2000; Burns et al., 2004). Almost twice as many men as women experienced delirium. Except in studies of hip fracture patients, where 80% of the patients were women, male gender has been listed by researchers as a predisposing factor in delirium. The presence of coexisting medical conditions is also a predisposing factor. In the present study, the comorbidity index for these patients was 2.2 (Brauer et al., 2000; Burns et al., 2004; Inouye, 2006). Twice as many cases of delirium were noted on the night shift as on the day shift. Whether or not the symptoms first occurred on the night shift is unknown, but the night shift was when the symptoms were recognized by the nurses. The majority of the cases were classified as hyperactive, which is typical.
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Many nurses define delirium in terms of agitated behavior and fail to recognize the hypoactive version. The sample was nearly equally divided between medical and surgical patients. The most common diagnoses in the medical patients were arthritis and back pain. It could be inferred that much of the pain in the medical group may have been chronic pain, lending support that unmanaged chronic pain as well as acute pain may be implicated in the precipitation of delirium. The most profound finding was the small amount of pain medication received during the 24 h before onset of delirium. We compared the amount received against the amount the patient could have received according to the physician order. Even when the amount received was compared with the expected amount to be used based on age, the patients who developed delirium were still undermedicated. The study finding of low amounts of PCA medication is of interest. This may be related to several factors, including higher efficacy of intravenous drug administration, difficulty in use of the pump by the elderly, or cultural and generational bias of some elders toward stoicism (Grass, 2005). Some older patients are fearful of using too much pain medication and may endure pain needlessly (Everett & Salamonson, 2005). Geriatric patients should be assessed preoperatively and immediately postoperatively to ensure that they can manage the pump both physically and cognitively. Learning to use the PCA concept requires sufficient preoperative mental status. Yet, not all surgeries are planned so that patients have the opportunity to learn PCA before surgery. Keita et al. (2003) suggested that older patients be given the Mini Mental State Exam (MMSE) before surgery. Those researchers also found that in a group of 40 patients aged over 70 years undergoing total hip replacement, the MMSE declined significantly 2 h after surgery and remained at that lower level for 48 h. This is a critical period of time. If the older patient cannot cognitively manage the PCA pump, pain may get out of control. This is supported by the experimental work of Crombez et al. (1996), 1997), who determined that pain interferes with task performance. If a patient is in severe pain, there will be cognitive interference, and the patient may not be able to complete the task of pushing the button on the PCA pump. Thus, the older patient’s ability to use the pump should be assessed frequently. It may be that neither PCA nor PRN medication is appropriate for older adults. Asher (2004) recommended that postsurgical pain medication be scheduled for older adults. Vaurio et al. (2006) found that older patients who used oral opioid analgesics on a
scheduled basis were at decreased risk of developing delirium compared with those who used intravenous PCA management of pain. The same is true with older medical patients who are in pain. They, too, should be assessed frequently for their ability to use the pump. A variety of medical and treatment-related factors could impinge on their mental status and affect their ability to use a PCA pump. Scheduled dosing of pain medication around the clock may be a better method of managing pain in hospitalized older patients. Review of the physician progress notes indicated that many of the cases of delirium were readily attributed to opioids. It was apparent that the amount of opioid the patient had received was not determined before discontinuation. Evidence demonstrates that most opioids do not cause cognitive changes. In the study by Lynch et al. (1998), cumulative opioid doses were not associated with an increased risk of delirium. Ersek, Cherrier, Overman, & Irving (2004) reviewed the empiric literature regarding the cognitive effects of opioids. From their systematic review of the literature, those authors concluded that the evidence reveals minimal to no significant cognitive changes associated with opioids. In a systematic review of postoperative patients by Fong, Sands, & Leung (2006), only meperidine was associated with increased delirium. There were no convincing data to indicate that morphine, fentanyl, or hydromorphone increased the risk of delirium. Similarly, in hip fracture patients, Morrison et al. (2003) demonstrated that opioids, with the exception of meperidine, do not precipitate delirium in patients with hip fracture. Although patients in earlier studies reported sedation and mental dullness, there were no marked deficits in cognition as measured by validated neuropsychiatric instruments. Many doctors and nurses believe that opioids should be used sparingly. They immediately assume that opioids are the culprit when elders experience delirium. More education is needed for all health care providers to destroy this myth and clarify the issue. Esper and Heidrich (2005) stressed the importance of evaluating all potential causes of delirium rather than quickly blaming the opioid as the causative factor. If the clinician rules out other factors, then it would be appropriate to change to an equianalgesic dose of another opioid rather than stopping all opioids. Eight of the patients received propoxyphene-N, and one received meperidine. There is a considerable amount of literature that links these drugs to delirium in elders (Fong, Sands, & Leung, 2006; Morrison, 2003). In their guidelines on pain management, the American Geriatrics Society (AGS) discourages the use of both medications with elders. Propoxyphene’s effi-
Pain Medication and Delirium
cacy is similar to acetaminophen alone, but because of drug accumulation it can have neuroexcitatory effects (AGS Panel on Persistent Pain in Older Persons, 2002). Propoxyphene or meperidine may have contributed to the delirium in these patients. Another serious finding of the present study was that patients with the predisposing risk factor of hearing impairment received the lowest amount of pain medication. This may reflect a communication issue. It may be that the older patient with a hearing impairment is not hearing how to use a PCA pump if ordered. He or she may not hear explanations from nurses on how to ask for PRN pain medication or may misunderstand the nurses when they ask about pain symptoms. This finding stresses the importance of using proper techniques in communicating with older patients with hearing losses or improving communication with devices such as pocket-talkers.
LIMITATIONS AND FUTURE RESEARCH One of the difficulties in conducting this study was related to retrieving charts where the physician had identified delirium as a diagnosis. Because this was a retrospective study, the study was totally dependent on clinician recognition and documentation of delirium. Delirium was rarely included in the discharge summaries. This problem in itself supports findings from the literature that delirium is often unrecognized in the hospital setting. This is partly due to lack of clinicians’ use of valid and reliable instruments to assess delirium. This may also be related to clinicians’ failure to appreciate the consequences of delirium. Underdiagnosis can lead to serious outcomes, such as complications, prolonged hospital stay, and even death. Routine use of a simple instrument, such as the Confusion Assessment Method or the Nursing Delirium Screening Scale, could improve recognition of delirium and reduce the associated morbidity and mortality (Gaudreau, Gagnon, Harel, Tremblay, & Roy,
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2005; Inouye, 2006; Inouye, Van Dyck, Alessi, Balkin, Siegal, & Horwitz, 1990). In hindsight, the study could have been improved if attention was given to pain intensity rating and appropriateness of medications prescribed. Additional insight would have been provided regarding adequate pain management. The design of the study is limited in that it is a retrospective record review, which is dependent on accurate documentation. Another limitation is lack of a comparison group. The outcomes of the study would be strengthened by comparing this group of patients with a matched group of patients who did not develop delirium. More information about the influence of lack of pain control and the development of delirium could be obtained. Another suggestion for future research would be to examine the appropriateness of use of the PCA pump for the geriatric patient. Many elders might do quite well, but others may experience difficulty. Unmanaged pain may contribute to cognitive impairment, and cognitive impairment may impact elders’ ability to use the PCA pump. A vicious cycle may ensue that could be interrupted by careful assessment. In conclusion, this was a descriptive study, and no association between delirium and pain can be determined from this design. The study did reveal that patients with pain who developed delirium had received only a fraction of the ordered pain medication during the 24 h before the onset of delirium. This provides a hint that there may be a relationship between inadequate pain management and development of delirium in medical patients with chronic pain as well as surgical patients with acute pain. Although the cause of delirium is multifactorial in most patients, it behooves all nurses to focus on adequate pain management in their elderly patients. If the patient is admitted with risk factors for development of delirium, unmanaged pain might be the additional factor that precipitates delirium.
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