Alcohol Withdrawal—Therapeutical Management in Surgical Patients with Upper Intestinal Bleeding

Abstract

Psychological dependence involves a desire to use a drug to avoid the unpleasant withdrawal syndrome that results from cessation of exposure to it. Alcohol withdrawal syndrome is one of the most feared complications of alcohol addiction and sometimes can be fatal if not treated properly. Withdrawal syndrome is characterized by neurological hyperexcitability, which can lead to severe psychological and neurological symptoms. A survey was conceived in order to monitor the efficiency of several drug associations (Clonidine, Midazolam, IV ethanol), which were administered at the beginning of intensive therapy admission of achohol addicts. By comparing the postoperative evolution parameters and complications incidences for these patients (such as the hospitalization duration in AIT department, the tracheobronchitis incidence, complications as sepsis, pneumonia and cardiac complications), we managed to determine which treatment is the most beneficial for these cases. Benzodiazepines are frequently used for pharmacological therapy of alcohol addicted patients. In our study Midazolam was very efficient, compared to other therapies. When administered for a maximum of 7 days, the inccidence of side effects remains minimal.

Introduction

Alcohol withdrawal syndrome is one of the most feared complications of alcohol addiction and sometimes can be fatal if not treated properly, mortality reaching up to 15%. Withdrawal syndrome is characterized by neurological hyperexcitability due to reduced GABA-ergic activity and increased glutaminergic and noradrenergic activity.

Excess alcohol consumption is a serious health problem, that not only affects the mental health of the persons concerned, but may contribute to multi-systemic structural and/ or functional alterations, such as digestive tract organs and annexes, heart and so forth.

In this study we intend to establish the benefit of the multiple mesures and drugs administered in order to prevent complications for these high risk patients.

Matherials and Methods:

A survey was conceived in order to monitor the efficiency of several drug associations, which were administered at the beginning of intensive therapy admission (Clonidine, Midazolam, i.v. ethanol). By comparing the postoperative evolution parameters and complications incidences for these patients (such as the hospitalization duration in AIT department, the tracheobronchitis incidence, complications as sepsis, pneumonia and cardiac complications), we managed to determine which treatment is the most beneficial for these cases.

Postoperative withdrawal syndrome prevention and treatment have been tested by substitution with alcohol (1-2 mg/dl), monotherapy with Midazolam (0.2-0.4mg/kg/h) or Clonidine (1-2mg/dl). 150 patients were classified in 3 groups whom was administered one of the 3 forms of treatment. The results of group which received alcohol substitution were considered reference for the comparison.

Results:

Statistical analysis of the results revealed that the group that received Midazolam monotherapy, showed best postoperative results, followed by a reduced number of withdrawal syndrome symptoms (with 45%), a shorter duration of hospitalization in AIT department (with 5.2 days), less respiratory complications, delirium tremens and lower mortality (6% versus 12%), when compared with i.v. achohol group.

The patients in the group that received Clonidine, necessitated supplementary sedation, usually with benzodiazepines. Even so, the results were still better then the group with received alcohol sustitution, with 32% reduction of withdrawal syndrome symptoms,a shorter duration of hospitalization in AIT department (with 4.5 days)and lower mortality (8% versus 12%).

Discusions

Alcohol addiction prevalence in surgical patients is very high. Addiction is a compulsion for rewarding stimuli (associated with positive reinforcement), which is essentially an intense desire or craving. Psychological dependence involves a desire to use a drug or perform a behavior to avoid the unpleasant withdrawal syndrome (negative reinforcement) that results from cessation of exposure to it [1,2,3]. Alcohol withdrawal syndrome is one of the most feared complications of alcohol addiction and sometimes can be fatal if not treated properly, mortality reaching up to 15% [1,4]. Addicted patients have a higher morbidity and exhibitmore complications, such as infections and cardiovascular complications. In these patients, the alcohol recede during hospitalization, the surgical stress, the hypotension, the hypoxia or the perioperative pain, may hasten the onset of withdrawal syndrome [1,5,6].

Surgeons tend to under-recognize psychiatric disorders until they interfere with evaluation and treatment. Often, a patient’s psychiatric history is not obtained or considered until problems arise post-operatively. Chronic alcohol abuse and withdrawal syndrome, are associated with severe postoperative complications as pneumonia, infections, difficult healing, sepsis, cardiac complications (heart failure, ischemia, arrhythmias) [7]. They also develop severe hemorrhages and require a higher volume of blood for transfusions [7,8].

Withdrawal syndrome is characterized by neurological hyperexcitability due to reduced GABAergic activity and increased glutaminergic and noradrenergic activity. There are also numerous mechanisms of cortical inhibitory pathways depression, leaving the excitatory pathways to function uncontrolled [1,9,10].

In these patients, postoperative complications risk can be minimized. Tonnensen proved in one survey, that a month withdrawal program that includes disulfiram, before surgery, decreases postoperative complications in patients that undergo gastrointestinal surgery [11]. Minimizing intraoperative stress also decreases postoperative morbidity [12]. Also, an important part belongs toadministrationof agents that decrease the production of cortisol (small alcohol doses, morphine, ketoconazole, propofol) [13].

Postoperative withdrawal syndrome prevention in patients with UIB

Part of the patients with UIB requires emergency surgery and therefore withdrawal syndrome prevention shortens the hospitalization in AIT department. During a survey, were used and compared more drug associations, which were administered at the beginning of intensive therapy admission: flunitrazepam-clonidine, chormethiazol-halperidol, flunitrazepam-haloperidol or ethanol, then being appreciated the hospitalization duration in AIT department, the tracheobronchitis incidence, complications as sepsis, pneumonia and cardiac complications. The patientswith chlormethiazol- haloperidol, developed tracheobronchitis [14]. Although benzodiazepines are recommended as first line treatment in withdrawal syndrome prevention, administration of iv ethanol, represents a prophylactic alternative in many AIT departments. Many claim that it would realize prevention, without excessive sedation as benzodiazepines. A comparison survey was realized, focusing on sedative effects. The survey conclusion was that ethanol has no advantage as against diazepam and that its efficiency was not proved [2,15]. Another survey proved that ethanol vapors inhalation, may reduce postoperative ethanol withdrawal syndrome symptoms if diazepam treatment doesn’t work [16]. Clonidine efficiency has been evaluated in intrathecal or oral administration as a supplement to spinal anesthesia with lidocaine, in postoperative withdrawal syndrome prevention. The conclusion was that 150 mg of intrathecal/oral clonidine prevent the onset of postoperative withdrawal syndrome, better than 10 mg of oral diazepam [17,18].

Treatment for the patient hospitalized for UIB, that presents ethanol withdrawal syndrome

An important percentage of the patients with UIB, presents at hospital admission or develop during hospitalization ethanol withdrawal, due to the high rate of chronic ethanol consumption in this group of patients.

Severe withdrawal syndrome risk factors are: the chronic alcohol consumption, history of generalized convulsions or delirium tremens, while symptoms as anxiety, unrest, tremor, excessive perspiration, altered state of consciousness, hallucinations, show a severe withdrawal syndrome [19]. Supportive measures have a major part in ethanol withdrawal patient management. Reevaluation of the patient’s state has to be done repeatedly, since many symptoms of the withdrawal coexist, can be mimed or complicated by other conditions, infections, trauma, metabolic disorders, hepatic failure, digestive hemorrhages. When we confront with altered mental state without a defined cause, we have to perform a lumbar puncture or a CT scan, in order to exclude other diagnostic possibilities, especially in patients with fever and withdrawal syndrome.

The patients need to be placed into a quiet place, in lateral position (swimmer position). It may be necessary for those patients who suffer from delirium tremens, for their protection and for those who take care of them. Blood volume deficits have to be calculated and replaced; if there are no contraindications, isotonic i.v. fluids are administered until the patients become clinically euvolemics. Before administering solutions that contain glucose, Thiamine 100 mg iv or im have to be administered in order to decrease the risk of Wernicke encephalopathy or Korsakoff syndrome.

Multivitamins and folate are used as a regular base. Potassium, magnesium, glucose, phosphate deficiencies have to be corrected if necessary. Among the criteria that lead to AIT admission, are:

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Patients older than 40 years, with concurrent diseases like heart failure, myocardial ischemia and pectoral angina;

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Hidroelectrolytic imbalances with EEG alterations, alterations of the acid base balance;

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Hemodynamic instability, respiratory failure, hypoxemia, hypercapnia;

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Severe infections;

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Gastrointestinal pathology, pancreatitis, superior digestive hemorrhage, peritonitis, persistent hyperthermia;

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Rhabdomyolysis, renal failure, delirium tremens history.

Table II. Doses.

Table II. Doses.

“Clinical Institute Withdrawal Assessment for Alcohol” revised score (CIWA- Ar) uses 10 terms to quantify the severity of withdrawal syndrome and allows the classification of the patients in 3 different categories: mild (no hospitalization required), moderate, severe. Severe forms require hospitalization in AIT hospital department [20,21,22].

This score is useful but not sufficient, most of the patients having associated comorbidities. It does not take in consideration delirium tremens, which could have other etiologies beside ethanol withdrawal. It’s a numeric scale which assigns to symptoms a value regarding their severity, but it’s quite subjective [23,24,25]. In refractory withdrawal, barbiturates are associated, especially phenobarbital. Propofol may be also used. The usage of phenobarbital and propofol, requires AIT monitoring and mechanical ventilation [26]. Among other pharmacological agents which have been proposed is Baclofen, a selective agonist of the GABA – B receptor and owns antispasmodic effects through this mechanism. It seems to be efficient as benzodiazepines [27].

The most used antipsychotics are phenothiazines and butirophenones, which decrease convulsions but have to be used with extreme caution. Antiepileptic drugs: in studies is used carbamazepine which is thought to be as efficient as lorazepame, but there is not enough evidence to certify its use [23,28,29,30].

Chlormethiazole is a drug related to thiamine, which acts as a sedative-hypnotic, muscle relaxant and anticonvulsant. Other proposed agents are sodium valproate, gabapentin, gama-hydroxybutyrate [1,31,32]. Other drugs, as beta-agonists or neuroleptics might bring some benefits, but cannot be used in monotherapy [33].

Beta-blockers increase the risk of hallucinations and clonidine increases the frequency of nightmares, while their efficiency is not well enough documented. Neuroleptic drugs increase the risk of convulsions. Magnesium sulfate or meprobamate have numerous side effects and their usage is not recommended. There are no specific recommendations regarding hydration. Excessive intake of sodium containing solutions, increases the risk of pulmonary edema in patients with cardiac diseases. B1 vitamin deficiency is frequent and may cause severe complication, that’s why oral intake of B1 vitamin is recommended, in high doses, in order to compensate poor absorption. IV administration is preferred if the patient has a seriously altered nutritional status or in severe complications as Gayet-Wernicke encephalopathy, even if there were reported important anaphylactic reactions after vitamin injection.

Reestablishing proper hydroelectrolitic balance, along with continuous monitoring of vital functions and respiratory support, if necessary, has the effect of decreasing mortality in delirium tremens below 3% [19,34,35,36].

Conclusions

Benzodiazepines are frequently used for pharmacological therapy of alcohol addicted patients. In our study Midazolam was very efficient, compared to other therapies. When administered for a maximum of 7 days, the inccidence of side effects remainsminimal [19]. They act on GABA-ergic receptors. Lorazepam, Oxazepam or Tamazepam are used frequently in patients with advanced hepatic diseases, because they lack metabolic effects and they have a short half-life. Oral administration is the preferred way of administration. If bewildered, the i.v. way is used. If not possible, Lorazepam i.m. is used. Young patients with little comorbidity may be only slight sedated. Old patients, with comorbidities must be sedated and monitored in AIT department. Symptomatic therapy is reserved for withdrawal symptoms and represents the choice for young patients. They receive lower doses of benzodiazepines and the treatment period is shorter.