Use of propofol as adjuvant therapy in refractory delirium tremens.

Delirium tremens is recognized as a potentially fatal and debilitating complication of alcohol withdrawal. Use of sedatives, particularly benzodiazepines, is the cornerstone of therapy for delirium tremens. But sometimes, very heavy doses of benzodiazepines are required to control delirious symptoms. We are reporting one such case of delirium tremens, which required very heavy doses of benzodiazepines and was ultimately controlled by using infusion of propofol. Thus propofol should always be considered as an option to treat patients with resistant delirium tremens.

Alcohol withdrawal syndrome (AWS) is a major cause of morbidity and mortality in the acute-care setting.[1] The spectrum of AWS ranges from minor symptoms such as insomnia and tremulousness to severe complications such as withdrawal seizures and delirium tremens.[2] Delirium tremens, the most serious manifestation of alcohol withdrawal, occurs in approximately 5% of hospitalized alcoholics, and a mortality rate approaching 15% has been reported.[3] Current diagnostic criteria for delirium tremens include disturbance of consciousness, change in cognition or perceptual disturbance developing in a short period, and the emergence of symptoms during, or shortly after, withdrawal from heavy alcohol intake. With the advances in the treatment modalities, the mortality rate has dropped to almost 0%-1% in some centers.[4]

Most patients undergoing alcohol withdrawal can be treated safely and effectively as outpatients. Pharmacotherapy involves the use of drugs that are cross-tolerant with alcohol.[5] Benzodiazepines, the agents of choice, may be administered on a fixed schedule or the one based on triggering of symptoms.[6] Carbamazepine is an appropriate alternative to a benzodiazepine in the treatment of outpatients with mild-to-moderate alcohol withdrawal symptoms. Medications such as haloperidol, beta blockers, clonidine and phenytoin may be used as adjuncts to a benzodiazepine.[2]

Of late, propofol has also been used as adjuvant to control refractory delirium tremens due to acute alcohol withdrawal.[378] But all reports on the use of propofol have emerged from abroad. No case of delirium tremens due to alcohol withdrawal, treated with propofol has been reported in India. Here, we are reporting a case of refractory delirium tremens treated with infusion of propofol.

CASE REPORT

A 32-year-old man with a history of alcohol abuse was admitted to the general medical unit because of altered mental status and agitation. He had complaints of repeated episodes of vomiting, tremors, passing highly colored urine and loss of appetite. He had no significant past history of medical/ surgical illness. He was a heavy alcoholic for the last 8 years; and 3 days back, he had taken some medicine from a de-addiction center in his village, but the identity of those medicines could not be ascertained. On examination, his conjunctivae were pale; he was anxious and had tremors. His blood pressure was 110/74, pulse rate was 94 and respiratory rate was 20 per minute. Abdominal examination revealed hepatomegaly. Biochemical investigations including liver function tests [serum glutamic oxaloacetic transaminase (SGOT), 126 IU; serum glutamic pyruvic transaminase (SGPT), 118 IU] and lipid profile [Low-density lipoproteins (LDL), 201 mg/dL; total glycerides (TGs), 186 mg/dL; total cholesterol, 498 mg/dL] were deranged. He had normal coagulation profile, normal renal function and serum electrolytes. HBsAg, Anti-HCV and HIV-ELISA were negative. Ultrasonography of the abdomen showed diffuse fatty liver with hepatomegaly (liver size, 19.8 cm).

In the ward, he was started on intravenous thiamine along with dextrose infusion, metoclopramide and pantoprazole. His minor withdrawal symptoms were controlled by giving lorazepam 5 mg on day 1. As his condition deteriorated, diazepam and lorazepam injections were also added. As on the 3rd day, delirious symptoms appeared, the patient was shifted to the intensive care unit (ICU). Due to poor response to benzodiazepines; propofol infusion was started. He was maintained on continuous infusion of propofol and lorazepam with intermittent boluses of diazepam and midazolam [Table 1].

Table 1

Sedative doses used to treat delirium tremens (up to day 7)

Patient was intubated and placed on mechanical ventilation. His sedation level was monitored using Richmond Agitation Sedation Scale (RASS).[9] Subsequently his condition improved, and he got extubated on the 8th day and was transferred back to the general medical ward on oral diazepam and thiamine, which had been started in the ICU. He was discharged after another 5 days and was referred to institutional rehabilitation center.

DISCUSSION

Cases of alcohol-withdrawal–induced delirium tremens requiring heavy doses of sedatives are common. Cases requiring heavy sedations/ benzodiazepines have been reported earlier also.[1011] Propofol has also been used earlier to control delirious symptoms, as an adjuvant.[378] But in India, there is no documented proof of use of propofol for this condition. The clinical utility of benzodiazepines is limited by their stimulation of the γ-aminobutyric acid receptors — an effect not shared by propofol, an anesthetic agent that induces a state of cooperative and conscious sedation. Thus in patients requiring high doses of sedatives for the treatment of delirium tremens, propofol should be considered as an option for adjuvant therapy; although the side effects of high-dose propofol infusion, viz., hypertriglyceridemia, acute pancreatitis, increased risk of infection and metabolic acidosis, should always be kept in mind while using propofol infusion for refractory delirium tremens.