Management of Delirium

April 2, 2007

Ms. B is a 44-year-old married African-American female who was diagnosed with locally advanced right breast cancer in 2002. Immunohistochemistry in the original tumor was estrogen- and progesterone-receptor-negative, HER2-positive. Her past medical history is significant for hypertension and miscarriage in 1995.

Ms. B is a 44-year-old married African-American female who was diagnosed with locally advanced right breast cancer in 2002. Immunohistochemistry in the original tumor was estrogen- and progesterone-receptor-negative, HER2-positive. Her past medical history is significant for hypertension and miscarriage in 1995.

Treatment Summary

After surgical consultation, it was decided that preoperative chemotherapy and radiation would be administered. Ms. B was started on doxorubicin/cychlophosphamide, followed by docetaxel (Taxotere). She underwent a modified radical right mastectomy with axillary dissection in 2003. She was found to have 2 positive nodes out of 14 and extensive necrosis of 7 additional nodes. After recovery from surgery, she underwent external-beam radiation therapy.

Ms. B did well until late 2004, when she was found to have progression in her left neck. Magnetic resonance imaging (MRI) revealed multiple masses in the supraclavicular region. She was started on single-agent capecitabine (Xeloda), as her tumors were noted to be HER2-negative.

Unfortunately, her disesase progressed on capecitabine and she was enrolled in a clinical trial in early 2005 using a tyrosine kinase inhibitor. She did well until mid-2005, when her cancer progressed further. She then received vinorelbine and her disease stabilized.

In spring 2006, she underwent an elective left mastectomy and bilateral breast reconstruction. Multiple infections and other complications after surgery resulted in postponement of chemotherapy during the summer. In fall 2006 her cancer was restaged and was found to have progressed in her neck and to have metastasized to the cerebellum and temporal lobes of the brain.

Ms. B developed simple partial seizures at home and was admitted to begin dexamethasone 4 mg every 6 hours and levetiracetam (Keppra) 500 mg bid. She was discharged after consultation with neurosurgery for treatment with gamma knife and surgical resection, which she declined. She instead received a course of whole-brain radiation. Her steroids were gradually tapered. In December 2006 she was admitted to the neurology ICU in status epilepticus. An MRI showed a decrease in previous lesions with a new parietal lesion and minimal edema without midline shift.

Ms. B was stabilized with phenytoin 100 mg tid, levetiracetam 1,000 mg bid, valproic acid 500 mg bid, and dexamethasone 4 mg every 6 hours, and transferred to oncology.

Nursing Management/Outcome

Upon admission to the oncology unit, a Mini-Mental State Examination (MMSE) was performed as well as a screening for delirium using a delirium screening tool. Ms. B scored low on the MMSE, with a score of 20/30. Points were lost for disorientation, calculation, recall, and copying a design. She was also noted to be drowsy but cooperative. Her delirium screening score was 4, which was positive. The diagnosis of delirium was confirmed by the oncologist. A delirium protocol, including twice daily delirium screening with interventions specific to delirium, was initiated.

Laboratory studies showed white blood cells 15,130/mm3, hemoglobin 12 g/dL; platelets 110/mm3; albumin 2.3 g/dL; BUN 20 mg/dL; creatinine 0.8 g/dL; sodium 135 mEq/L; potassium 4.5 mEq/L; glucose 286 mg/dL; magnesium 2.0 mEq/L; calcium 9.5 mg/dL; total bilirubin 0.7 µmol/L. Antiseizure medication levels were noted to be within therapeutic range. A urine culture was positive for Escherichia coli, and her EKG was normal.

Ms. B's medications at this time, in addition to steroids and antiseizure medications, included ciprofloxacin for a urinary tract infection, subcutaneous insulin as needed for steroid-induced diabetes, oxycodone and hydromorphone hydrochloride for headache, lorazepam for agitation, diphenhydramine hydrochloride for sleep, and metoclopramide for nausea.

On the evening of her transfer, she was noted to go from her initial drowsiness to being agitated with visual hallucinations. She was also more inattentive and disoriented. Lorazepam IV 1 mg was given for agitation and diphenhydramine IV 25 mg was administered for sleep. She initially calmed after receiving both medications, but on waking was more agitated with increased hallucinations. An observer was placed at the bedside to assist and protect the patient.

The next morning Ms. B's medication came under review during multidisciplinary rounds. Diphenhydramine, lorazepam, and metoclopramide were discontinued, and haloperidol was begun at 1 mg po every 8 hours around the clock for her hallucinations/agitation and nausea/vomiting. Her pain medication was changed to single-agent hydromorphone at 0.5 mg po every 3 to 4 hours as needed. The dexamethasone was decreased to 2 mg every 6 hours to minimize side effects. Tighter management of her blood sugars was instituted. Ms. B's family was encouraged to be at her bedside to assist with frequent reorientation and provide support. A dry erase board with the date, her location, and her caregivers' names was maintained within her sight.

Throughout the next week, her headaches were eliminated with the prn hydromorphone. She experienced no additional seizures or nausea/vomiting. The hallucinations and agitation subsided, and the haloperidol was gradually decreased to 0.5 mg bid. The urinary tract infection resolved and her blood glucose improved with interventions to obtain tighter control (glucose < 180 mg/dL). Her MMSE score had improved to 24/30, but decreased again as her status deteriorated. She became drowsier, remained disoriented and inattentive, but had periods of alertness and clarity in which she conversed with her family.

Ms. B gradually became increasingly somnolent and died peacefully 1 week after admission to the oncology unit, with her family at her bedside.

Discussion

Delirium is one of the most common complications seen in hospitalized oncology patients, but it is often misunderstood, unrecognized, or misdiagnosed.[1] Delirium is an acute clinical syndrome in which cognitive malfunctioning of the brain is caused by medical conditions or their treatments. It can develop very quickly or over several days, and can last for a few hours to days, weeks, or months. The pathophysiology of delirium is not well understood.[2]

The hallmark signs of delirium include sleep/wake cycle disturbance (sleepiness during the day and wakefulness at night), impaired cognition (disorientation; poor concentration; impaired memory, especially short-term memory;
impaired written/verbal language), disturbances of consciousness or "clouding of consciousness" (inability to manage attention and have clear awareness even when awake), and symptom fluctuation (symptoms wax and wane, although as the delirium worsens less fluctuation will be seen).[2-4]

Because nurses generally spend more time with patients than other caregivers, they are in the best position to recognize the waxing and waning of the symptoms of delirium.[5] In addition to the above noted signs, hallucinations, illusions, delusions, and strong emotional responses often occur in delirious patients.[2,3]

There are three types of delirium: hyperalert-hyperactive, hypo-alert-hypoactive, and mixed, in which the patient exhibits symptoms of both. The patient is usually drowsy in the hypoalert state and has problems generating attention. In the hyperactive state, the patient is usually restless and aroused but cannot sustain attention. The hyperalert state of delirium is rarely missed, but the hypoalert state is often not recognized and may be mistaken for fatigue or depression.[2,6,7]

The MMSE is a quick, excellent tool that can be used to evaluate cognitive function or the degree of cognitive impairment.[8] There are other delirium screening tools that can be used at the bedside. The Confusion Assessment Method (CAM), the CAM-ICU, and the Intensive Care Delirium Screening Checklist[6,9,10] are all useful tools.

The causes of delirium are numerous. Delirium is often caused by infections; medications (eg, opiates, anticholinergics, steroids, benzodiazepines, antibiotics, anticonvulsants); metabolic or endocrine abnormalities; intracranial problems, including lesions, trauma, hemorrhages, and epilepsy; and alcohol or benzodiazepine withdrawal syndromes. When possible, elimination of the cause(s) hastens the resolution of the delirium.

Treatment and Management

Treatment and management of delirium should include the following five points: recognition, protection of the patient, correction of the cause(s), optimization of the environment, and treatment of any agitation.[2,4] The successful treatment of delirium requires an interdisciplinary team.

Recognition of delirium is paramount. Ms. B exhibited all the classic signs of delirium. Using the MMSE and a screening tool assisted the nurses in recognizing delirium on admission, so that the oncologist could promptly diagnose it.

Delirious patients must be protected, as they are at high risk for self-injury. When she became agitated, Ms. B was assigned an observer to protect her from harming herself. Bed alarms can also be helpful; restraints should only be used as a last resort as they often cause more agitation. It is important to notify all staff of the presence of delirium. Patients with delirium need simple instructions and explanations, especially before they are touched by caregivers. A family member should be present for all discussions, consents, and teaching, as the patient is likely to misunderstand or forget parts of conversations.

The cause(s) of the delirium must be recognized and removed immediately if possible. In Ms. B's case, possible causes of her delirium included infection (the urinary tract infection), hyperglycemia, and medications. Her medications included opiates, steroids, anticholinergics (diphenhydramine), antibiotics (ciprofloxacin), and antiseizure medications. Certainly Ms. B's brain lesions and history of whole-brain radiation made her more susceptible to becoming delirious. The treatment of her infection and the stabilization of her blood sugars and seizures helped to lessen her delirium.

The comprehensive medication review and initiation of medication changes also contributed to her improvement. As illustrated here, Ms. B was on some medications (steroids, opiates, antibiotics, and antiseizure medications) that were pertinent to her treatment and could not be discontinued. When medications cannot be eliminated, using smaller doses (steroids) or only one type of medicine (opiates) can make a difference.

The environment should be optimized to support the delirious patient. Appropriate lighting at all times and orientation props such as clocks and calendars should be used. Familiar objects such as pictures can be placed at the bedside.

Treating agitation should be done by first assessing possible causes (eg, pain, urinary retention), then using appropriate medications (eg, neuroleptics like haloperidol, risperidone [Risperdal], or olanzapine [Zyprexa] or benzodiazepines such as lorezepam). Neuroleptics can help calm the patient and treat hallucinations, illusions, or delusions. Benzodiazepines can be helpful in treating agitation but not hallucinations, illusions, or delusions. Benzodiazepines shoudl be the first choice for delirium not caused by alcohol or benzodiazepine withdrawals or if neuroleptics cannot be used, such as in cases of QT wave prolongation or extrapyramidal symptoms. Benzodiazepines can, at times, worsen delirium so monitoring of the patient for increased confusion and agitation after a dose is given is important.

Summary

Oncology providers are faced with delirium on a daily basis in both the inpatient and outpatient settings. Using appropriate screening tests and a comprehensive delirium safety protocol can empower both providers and family members and assist in the protection of patients. While delirium cannot always be prevented, knowledge of its pathophysiology, prevention, and treatment strategies can minimize the effects and possibly shorten the duration. Treating Ms. B's delirium and agitation allowed her to spend her remaining time peacefully with her family.

To access the refererences for this article, go to http://www.cancernetwork.com/nurses-edition