|Year : 2015 | Volume
| Issue : 3 | Page : 89-94
Delirium tremens in the elderly: Emerging role of dexmedetomidine
Vishal Sehgal1, Sukhminder Jit Singh Bajwa2, John A Consalvo3, Anurag Bajaj4, Rinku Sehgal4
1 Department of Internal Medicine, University of South Carolina, Greenville, South Carolina, USA
2 Department of Anesthesiology and Intensive Care Medicine, Gian Sagar Medical College, Patiala, Punjab, India
3 Department of Emergency Medicine, Regional Hospital of Scranton, Pennsylvania, USA
4 WCGME, Scranton, PA, USA
|Date of Submission||27-Jan-2015|
|Date of Acceptance||20-Apr-2015|
|Date of Web Publication||8-Jun-2015|
Dr. Sukhminder Jit Singh Bajwa
House No - 27-A, Ratan Nagar, Tripuri, Patiala - 147 001, Punjab
Source of Support: None, Conflict of Interest: None
| Abstract|| |
The elderly are more predisposed to depression, which puts them at high risk for alcohol abuse and alcohol-related disorders such as delirium tremens (DTs). But its clinical presentation is often complicated by underlying comorbid conditions, such as congestive heart failure (CHF), atrial fibrillation (AF), sepsis, chronic kidney disease (CKD), electrolyte imbalance, dementia, malglycemia, nutritional deficiencies, and polypharmacy. The current review is aimed at defining the appropriate management of these clinical conundrums that frequently accompany alcohol abuse in the elderly, leading to increased morbidity and mortality. It also emphasizes the emerging role of dexmedetomidine in treating the elderly with DTs.
Keywords: Alcohol abuse, atrial fibrillation (AF), chronic kidney disease (CKD), delirium tremens (DTs), dexmedetomidine, elderly, malglycemia, polypharmacy
|How to cite this article:|
Sehgal V, Bajwa SJ, Consalvo JA, Bajaj A, Sehgal R. Delirium tremens in the elderly: Emerging role of dexmedetomidine. Int J Nutr Pharmacol Neurol Dis 2015;5:89-94
|How to cite this URL:|
Sehgal V, Bajwa SJ, Consalvo JA, Bajaj A, Sehgal R. Delirium tremens in the elderly: Emerging role of dexmedetomidine. Int J Nutr Pharmacol Neurol Dis [serial online] 2015 [cited 2020 Jan 21];5:89-94. Available from: http://www.ijnpnd.com/text.asp?2015/5/3/89/158319
| Introduction|| |
There has been a huge increase in the elderly population, and the health-care infrastructure is ill-equipped to handle the massive surge in the elderly population across the world. With aging, there is multisystem decline in body functions. Most notably, there is a linear decline in renal function after the age of 30 when the body attains the peak body mass. In addition, the elderly have multiple comorbidities, which accelerate the decline, resulting in decreased renal and hepatic clearance of drugs. Their cytochrome and P-gp (permeability glycoprotein) systems slow down with aging and there is potential for drug toxicity secondary to accumulation. Further, there are medications that could suppress the cytochrome and P-gp systems and slow the metabolism of the drugs. On the other hand, if the elderly are on cytochrome- or P-gp-inducing medication, it may lead to accelerated metabolism of drugs. This would lead to subtherapeutic drug levels. The scenario is somewhat complicated, as the elderly are often on polypharmacy. 
The elderly in particular are more predisposed to depression and alcohol-related disorders. , Delirium tremens (DTs) is a severe form of alcohol withdrawal manifesting in autonomic hyperactivity and a change in mental status with global confusion. It is a medical emergency with high mortality, and more so in the elderly. This indicates a critical need for prevention, early diagnosis, and appropriate treatment.
Chronic alcohol abuse alters the neurotransmitter system in the brain [Figure 1]. The effects include the altered release of endogenous opiates, activation of GABA receptors leading to increased γ-aminobutyric acid (GABA) inhibition, and upregulation of N-methyl-N-aspartate (NMDA) and glutamate receptors. It also interferes with serotonin and dopamine receptors. Withdrawal from alcohol leads to a loss of the inhibitory effect of GABA, resulting in increased autonomic activity. This may manifest in tremors, increased sweating, tachycardia, and seizures. In addition, the lack of inhibition from NMDA receptors leads to seizures and delirium.
|Figure 1: Effect of chronic alcohol abuse and acute alcohol withdrawal on the neurotransmitters|
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| Risk Factors|| |
There are many risk factors that predispose an individual to DTs, old age being one. , Other risk factors include a prior history of DTs, medical comorbidities, hypokalemia, regularity of alcohol use, and prior history of detoxification. In a study by Lee et al., a prior history of DTs with tachycardia had a high predictive value for the development of DTs during hospitalization.  The risk factor profile has wide variability. About 9% of adults in the USA have alcohol abuse disorder, but less than 50% develop withdrawal symptoms. Only 5% patients with alcohol withdrawal develop DTs.  It is very uncommon in the pediatric age group but much more common in the elderly. This is because the physiological substrate needed to develop DTs takes time to develop.
| Clinical Presentation|| |
Elderly patients often present to the hospital for non-alcohol-related causes. , The cause of presentation in the emergency room (ER) is usually a comorbidity. , This often leads to delay in diagnosis and a longer length of hospital stay secondary to a more complicated clinical course.  Often, patients are seen in postoperative settings. , Acute alcohol intoxication or DTs could be complicated by severe sedation, respiratory depression, electrolyte imbalance, hepatic encephalopathy, hypoglycemia, hypophosphatemia, pneumonia, and cardiac arrhythmias [Figure 2]. , Cardiac arrhythmias are similar in alcohol intoxication and alcohol withdrawal syndrome (AWS). Arrhythmias could be tachy-arrhythmias or brady-arrhythmias. Tachy-arrhythmias may manifest as atrial fibrillation (AF), torsades de pointes, or ventricular tachycardia.  Additionally, due to increased sympathetic activity, the QT interval may be prolonged. , Brady-arrhythmias usually manifest as sinus bradycardia. Takotsubo cardiomyopathy has also been reported in DTs.  Even a single episode of alcohol intoxication has been related to increased mortality secondary to cardiac arrhythmias. 
|Figure 2: Clinical conundrums in the management of delirium tremens (DTs) in the elderly|
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Mortality in DTs may vary in the range of 5-15%. The most common cause of death is cardiac arrhythmias and its rate is likely to be higher in the elderly. , In a recent study by Grover et al., mortality from DTs was found to be as high as 18% within 4 days of hospitalization. 
AWS occurs in varying degrees of severity and may be subclassified as minor withdrawal, major withdrawal, withdrawal seizures, and DTs. Minor withdrawal is manifested as autonomic dysfunction with tremulousness, vomiting, sweating, tachycardia, and labile hypertension. Major withdrawal has features of minor withdrawal and hallucinations that may be auditory or visual. Major withdrawal is associated with a high incidence of rehospitalization after discharge from the hospital.  Withdrawal seizures may occur up to 48 h after cessation of alcohol use. They are major motor seizures and are generalized but brief. If left untreated, multiple seizures may occur. About 3% of patients go on to develop status epilepticus. Seizures might be the only sign of withdrawal and could potentially progress to DTs. If the seizures are focal or there is a history of trauma, the condition is unlikely to be related to withdrawal.
DTs is the most profound manifestation of alcohol withdrawal and manifests as profound global confusion along with major withdrawal or/and seizures.  DTs often manifests with significant comorbidities. A detailed history is always desirable, but this is usually not feasible, as the patient may not be able to give any meaningful history secondary to global confusion.
| Management|| |
Vigorous screening for alcohol-related disorders and scales to assess the severity of alcohol withdrawal are needed for all elderly individuals admitted to the hospital irrespective of the admission diagnosis. ,,,,,, Clinically, the most validated tool to assess for AWS is the Clinical Institute Withdrawal Assessment for Alcohol, revised (CIWA-AR) scale. It uses 10 variables to assess the severity of AWS. The 10 variables are nausea/vomiting, sweating, anxiety, agitation, tremor, headache, auditory disturbance, visual disturbance, tactile disturbance, and orientation. If the score is more than 20 it indicates possible severe withdrawal, and if score is less than 10 it is likely to be mild withdrawal. The earlier the treatment is started, the faster the recovery. , In the elderly, comorbidities more often than not complicate the clinical presentation of DTs and are one of the main determinants of mortality in this group, along with severity of DTs. , Other causes of global confusion need to be considered that might be the cause of delirium or could potentially complicate the clinical manifestation of DTs.
Congestive heart failure (CHF) is the most common cause of admissions to hospitals in the USA.  The hypermetabolic state of AWS may actually worsen the underlying CHF, which might mask the diagnosis of DTs. In addition, there may be concomitant hyponatremia, which may cause global confusion. Underlying dementia could complicate things further. AF is often seen concomitantly in patients with CHF. It could be a manifestation of underlying thyroid disorders, which is the secondmost common endocrinopathy in the elderly after diabetes mellitus (DM). AF has a worldwide prevalence of 1% and is much more common in the elderly.  It could potentially complicate the clinical presentation, diagnosis, and management of DTs. The tachycardia associated with DTs may be wrongly ascribed to poorly controlled AF. If hemodynamic instability is there it might be prudent to hold off on new oral anticoagulants (NOAC), as they need to be dosed renally and have significant drug interactions. , Based on the renal function, these NOAC may need dose titration or may need to be held. Short-acting anticoagulants such as unfractionated i.v. heparin may be more appropriate in these clinical settings.
In elderly individuals, sepsis frequently manifests as global confusion, especially if there is underlying dementia. ,, Empiric antibiotics and work-up for sepsis should be considered in all elderly patients with delirium. Hospitalization accentuates the risk of hospital-acquired infections (HAI) in the elderly, and they are also at high risk for antibiotic resistance and pressure sores.  Therefore, patients need to be evaluated for HAI on a regular basis. Additionally, the Centers for Disease Control and Prevention (CDC) has published three levels of alert to define the severity and urgency of antibiotic resistance in the population.  While prescribing drugs, antibiotic resistance as defined by the CDC needs to be considered along with the local hospital antibiogram. This would help prevent antibiotic failure and minimize the development of Clostridium difficile resistance to antibiotics.
It is difficult to define renal function in the elderly, as most of the equations rely on creatinine for calculation of the kidney function. In the elderly this could be highly inaccurate because of the individuals' low muscle mass. , Patients often present with acute kidney injury in chronic kidney disease (CKD). CKD is a marker of increased mortality in the elderly. All the drugs have to be carefully titered based on the dynamic renal function changes in the critically sick elderly. The elderly also have underlying electrolyte imbalance, which may be worsened with alcohol-related dehydration.
More than 25% of elderly individuals in the USA are diabetic.  The elderly are more predisposed to hypoglycemia because of impaired counterregulatory mechanisms. Hypoglycemia could complicate the clinical hospital course in both the diabetic and nondiabetic elderly. , In nondiabetics, hypoglycemia may be a manifestation of underlying CKD. Alcohol intoxication and sepsis are other common causes of hypoglycemia in the nondiabetic elderly. Noniatrogenic hypoglycemia is a marker of increased mortality and should alert the clinician to impending clinical worsening.  Neuroglycopenic clinical manifestations of hypoglycemia predominate in the elderly and often mimic AWS.  All long-acting oral hypoglycemics should be stopped at this point. An individualized insulin regime should be started depending on the clinical scenario. Long-acting insulin and sulfonylureas are responsible for most cases of hypoglycemia and should be reassessed in the inpatient settings. Additionally, uncontrolled hyperglycemia with the acute stress of AWS could potentially precipitate ketoacidosis in the diabetic elderly. ,, Again, a diagnosis of AWS may be missed because of, dementia, lack of history, and multiple confounding clinical conundrums. Nutritional deficiencies may or may not be related alcohol abuse.  Thiamine is useful in preventing Wernicke's encephalopathy. The goal should be to give thiamine within 2 h of diagnosis and to continue it for 30 days.  There is no evidence that proves the benefit of treating any other nutritional deficiency in the acute care setting.
The elderly frequently are on polypharmacy and potentially inappropriate medications. This exposes them to drug interactions and consequent, lifethreatening arrhythmias.  These individuals are often on chronic medications that could potentially prolong the QT interval [Table 1]. Hospitalization complicates the picture further, as more medications are added and the potential for drug interactions increases. Also, in DTs, because of electrolyte imbalance and underlying autonomic instability, QT prolongation may be seen. Antipsychotics are sometimes used for psychotic symptoms associated with delirium both alcohol- and non-alcohol-related. They lower the severity but not the incidence of delirium. ,, They are also associated with prolonged QT interval and hypotension. They have been associated with increased mortality in elderly dementia patients.  Prior to prescribing the use of haloperidol, it would be appropriate to make sure that there is no electrolyte imbalance and to do a screening electrocardiogram (EKG) to rule out underlying QT prolongation. This complicated scenario demands extreme caution and close monitoring if antipsychotics have to be used in the elderly. There are limited data regarding the use of atypical antipsychotics. 
Benzodiazepines remain the drug of choice for treatments in all stages of alcohol withdrawal. , However, it is not to be used in non-alcohol-related delirium, and this reinforces the importance of early diagnosis. Benzodiazepines act on the potentiating effect of GABA receptors just like alcohol. Long-acting drugs such as diazepam and chlordiazepoxide should be avoided in the elderly due to the high chance of accumulation. Shorter-acting drugs such as lorazepam are the preferred drugs in the elderly with DTs due to their short half-life.  A symptom-triggered approach versus standard protocols has been used successfully in the treatment of DTs. If a symptom-triggered approach is used, the drugs should be titered based on the CIWA-AR. In the elderly, dose and frequency need to be individualized, and if a fixed dose is used, it should be held for sedation. ,,,,,,,,,,,,
When excessive sedation is a concern with benzodiazepines, dexmedetomidine may be used, which is a highly selective, centrally acting alfa2 agonist. ,,, It does significantly decrease the need for benzodiazepines. It has anxiolytic, analgesic, and sedative properties but causes no respiratory depression. It has been associated with decreased delirium in critically ill patients. Bradycardia and hypotension may be seen on initial administration.  However, these effects may actually be beneficial in the hyperadrenergic state associated with DTs. It has been implicated in QT prolongation, and appropriate screening should be done prior to its use in elderly patients. 
Barbiturates and propofol may be considered in people refractory to benzodiazepines. They also act on the GABA and NMDA receptors. However, these drugs are associated with a higher incidence of hypotension and respiratory depression, and their use is best avoided in elderly patients with DTs.
| Conclusion|| |
All elderly individuals admitted to the hospital need to be diligently screened for alcohol-related disorders. Clinical conundrums associated with DTs in the elderly need to be addressed, which could potentially help reduce the mortality and morbidity associated with DTs.
Benzodiazepines remain the drug of choice for AWS, but excessive sedation remains a concern. Dexmedetomidine is a promising new drug and its use in AWS in the elderly is likely to be expanded as more data become available.
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[Figure 1], [Figure 2]