Withdrawal Syndromes Clinical Presentation

In addition to documenation of presenting complaints, essential elements of the history in withdrawal syndrome include the following:

• Type of drugs ingested over the long term
• Duration of addiction
• Time of last ingestion
• Reason for the patient's cessation of the drug
• Alternative treatments used to relieve withdrawal symptoms
• Previous withdrawal symptoms and their severity

Serious comorbid conditions can be inciting events for reasons for cessation of alcohol and should be thoroughly investigated. In patients admitted for reasons other than withdrawal (eg, myocardial infarction [MI], multiple trauma), obtaining a history of illicit drug and alcohol abuse is important, as it can assist with anticipating the need for treatment of withdrawal syndrome(s).

Alcohol withdrawal

Patients have typically abused alcohol on a daily basis for at least 3 months, or they have consumed large quantities for at least 1 week (ie, binge drinking). Withdrawal symptoms appear within 6-12 hours after individuals cease or decrease alcohol intake and are usually relieved by consuming additional alcohol.

The hallmark of alcohol withdrawal is a continuum of signs and symptoms ranging from simple tremulousness to DT. The spectrum varies greatly, and symptoms overlap in time and duration. Therefore, defining a constellation of manifestations ranging from mild to severe is most clinically useful.

Mild withdrawal usually occurs within 24 hours of the last drink and is characterized by the following:

• Tremulousness (shakes)
• Insomnia
• Anxiety
• Hyperreflexia
• Diaphoresis
• Mild autonomic hyperactivity
• GI upset

Moderate withdrawal usually occurs 24-36 hours after the cessation of alcohol intake and includes the following:

• Intense anxiety
• Tremors
• Insomnia
• Excessive adrenergic symptoms

Severe withdrawal usually occurs more than 48 hours after a cessation or decrease in alcohol consumption and is characterized by the following:

• Profound alteration of sensorium, including disorientation, agitation, and hallucinations
• Severe autonomic hyperactivity, including tremulousness, tachycardia, tachypnea, hyperthermia, and diaphoresis

Predictors of severe alcohol withdrawal syndrome include the following ^[5] :

• Past history of severe withdrawal
• Thrombocytopenia
• Hypokalemia

As many as 25% of patients with a prolonged history of alcohol abuse have alcoholic hallucinosis. Alcoholic hallucinosis can occur 24 hours after the last drink and continues for about 24 hours.

Symptoms consist of persecutory, auditory, or (most commonly) visual and tactile hallucinations; however, the patient's sensorium is otherwise clear. In the early stage, the patient recognizes frank hallucinations. However, in the advanced stage, these hallucinations are perceived as real and may provoke extreme fear and anxiety. The patient can be seen pulling at imaginary objects, clothing, and sheets, for example. Hallucinosis is not necessarily followed by delirium tremens (DT).

Approximately 23-33% of patients with significant alcohol withdrawal have alcohol withdrawal seizures ("rum fits"). Features of these seizures are as follows:

• Seizures are usually brief, generalized, tonic-clonic in nature, and without an aura. They occur in a cluster of  one to three seizures with a short postictal period. Partial seizures are not uncommon. In 30-50% of patients, the seizures progress to DT.

• The incidence peaks 24 hours after the most recent alcohol ingestion.

• Seizures typically terminate spontaneously or are easily controlled with benzodiazepines.

• Status epilepticus may occur in 3% of alcohol withdrawal seizures and should prompt an investigation for other causes, as people with alcoholism are prone to head injuries, chronic idiopathic epilepsy, and meningitis.

DT, the most intense sign of alcohol withdrawal, occurs 48-72 hours after the last drink. Features of DT are as follows:

• DT includes all early and intermediate symptoms of alcohol withdrawal but with the additional feature of a profoundly altered sensorium (disorientation, agitation, and hallucination)

• Severe autonomic derangements (including diaphoresis, tachycardia, tachypnea, and hyperthermia) are common

• DT may present without preceding seizures

To blunt the effects of alcohol withdrawal, persons who cannot obtain regular alcoholic beverages because of financial reasons may resort to ingesting other substances, as follows:

• Ingestion of isopropyl alcohol is common

• Other alcohols (eg, methanol, ethylene glycol) are rarely ingested.

• Ingesting cough syrup containing large amounts of alcohol may cause inadvertent acetaminophen toxicity

• The following substances have a sufficient alcohol concentration to mitigate the effects of withdrawal: isopropyl alcohol, cough syrup, hand sanitizer, mouthwash, methanol, and ethylene glycol.

Sedative-hypnotic withdrawal syndrome

Features include the following:

• Discontinuation of benzodiazepines, barbiturates, and other sedatives or hypnotics after long-term use produces withdrawal symptoms resembling those of alcohol withdrawal syndrome

• The morbidity/mortality is closely related to that of alcohol withdrawal syndrome

• Sedative-hypnotic withdrawal syndrome is characterized by pronounced psychomotor and autonomic dysfunctions

• Catatonia may occur with benzodiazepine withdrawal, as well as clozapine withdrawal ^[6]

• Symptoms usually occur 2-10 days after abrupt discontinuation of the drug, depending on its half-life

Gamma-hydroxybutyrate withdrawal

Gamma-hydroxybutyrate (GHB) withdrawal syndrome involves the following ^[7] :

• GHB and its precursors (gamma-butyrolactone, 1,4'-butanediol) are reported to induce tolerance and produce dependence

• These drugs are most commonly abused by young adolescents in dance clubs and rave parties

• Many users have mild withdrawal symptoms on discontinuing the drug; the symptoms resemble those of sedative-hypnotic withdrawal syndrome and are characterized by mild and brief autonomic instability with prolonged psychotic symptoms

• Severe withdrawal occurs following long-term heavy use; symptoms are similar to those of alcohol withdrawal syndrome, but delirium occurs earlier, while seizures (7%) and rhabdomyolysis (7%) rarely occur ^[8]

Opioid withdrawal

Patients experiencing opioid withdrawal can usually provide an accurate history of their usual dose, of the timing of their last dose, and of any other current symptoms. The clinical problem is in differentiating symptoms associated with opiate withdrawal from symptoms that may reflect an underlying medical illness.

In general, opioid withdrawal does not directly cause life-threatening symptoms, seizures, or delirium.

Opioid withdrawal syndrome may resemble a severe flulike illness. The syndrome is characterized by the following:

• Rhinorrhea
• Sneezing
• Yawning
• Lacrimation
• Abdominal and leg cramping
• Piloerection (gooseflesh)
• Nausea and vomiting
• Diarrhea
• Mydriasis
• Myalgias
• Arthralgias

Altered mental status, disorientation, hallucinations, and seizures, which are characteristic of DT, are not seen in opioid withdrawal.

The half-life of the opioid causing withdrawal syndrome determines the onset and duration of symptoms. For example, heroin and methadone withdrawal symptoms peak in 36-72 hours and 72-96 hours, respectively, and may last for 7-10 days and at least 14 days, respectively.

In addition to withdrawal syndrome, the differential diagnosis in patients with a history of long-term intravenous (IV) drug abuse must include the host of infectious problems to which these patients are susceptible, including but not limited to the following:

• Endocarditis
• Septic emboli
• Osteomyelitis
• Septic arthritis
• Abscesses (ie, psoas, brain, and epidural)
• Viral hepatitis

Stimulant withdrawal

Stimulant (cocaine and amphetamine) withdrawal, or wash-out syndrome generally does not directly cause life-threatening symptoms, seizures, or delirium. Features include the following:

• This syndrome resembles severe depressive disorder

• Manifestations include dysphoria, excessive sleep, hunger, and severe psychomotor retardation, whereas vital functions are well preserved

• The patient is typically in deep sleep with normal vital signs, and he or she may have a history of crack-cocaine binging and similar episodes ("crashes") in the past

• Patients may be so motivated to do nothing but sleep deeply that another cause for the patient's lack of responsiveness is suspected; in this case, a gradual full recovery and a negative workup would be expected

• Depression, mood, and anxiety symptoms improve over the first week but may persist for up to 2 weeks ^[9]

Thorough physical examination is important, given the multisystemic effects of alcohol withdrawal, the wide variety of potential medical diseases associated with alcoholism, and the patient's often limited ability to provide an accurate history. Although a complete physical examination may have to be deferred until after resuscitation, the treatment of seizures, and/or sedation for severe agitation, this examination must be completed as soon as possible with the goal of detecting end-organ damage resulting from the effects of withdrawal as well as other underlying conditions.

Vital signs may include the following:

• The central adrenergic storm that occurs during alcohol withdrawal results in hyperventilation, tachycardia, hypertension, tremor, hyperthermia, and diaphoresis.

• Hyperthermia is common in severe alcohol withdrawal because of psychomotor agitation.

• Hypothermia can be seen with Wernicke encephalopathy.

Head and neck findings may include the following:

• Stigmata of chronic alcoholism (eg, flushed facies, vascular spider angiomata) may be present

• Paralysis of extraocular muscles and nystagmus may indicate Wernicke encephalopathy or other intracerebral processes; these findings are important because they represent an opportunity to diagnose a readily treatable condition

• Dentition is often neglected and may be a source of infection

• Tongue lacerations may indicate previous seizures or other trauma; the tongue is also a reliable place to look for withdrawal tremors

• Determine if evidence of head and facial trauma (eg, signs of basilar skull fracture) is present, as this represents a common opportunity for critical intervention

Chest findings in alcohol withdrawal may include the following:

• Tachypnea is expected during moderate-to-severe alcohol withdrawal, but dyspnea is not expected.

• Rib fractures are common in people with chronic alcoholism; recent rib fractures may be associated with pneumothorax.

• Note signs of pneumonia (eg, cough, sputum production, fever, localized wheezing, consolidation, respiratory distress).

• Kussmaul respiration may represent underlying metabolic acidosis. Potential causes in the setting of alcohol withdrawal include alcoholic ketoacidosis (AKA) and ingestion of toxic alcohols or medications that result in metabolic acidosis (eg, methanol, ethylene glycol, salicylate). Consumption of rubbing alcohol (isopropyl alcohol) does not cause metabolic acidosis or Kussmaul respiration.

Chest findings in opiate withdrawal may include the following:

• Patients with opiate addiction are at high risk for HIV infection and are susceptible to AIDS-related pneumonias, particularly those due to Pneumocystis jiroveci and Mycobacterium tuberculosis.

• Note symptoms and physical evidence of cough, hemoptysis, fever, and tachypnea

Cardiac findings may include the following:

• Tachycardia and hypertension are common and expected during alcohol withdrawal

• A murmur (particularly a right-sided tricuspid or pulmonic murmur) and fever in a patient with a history of intravenous drug abuse is worrisome because of the possibility of endocarditis. Blood cultures and an echocardiography are indicated in this circumstance to determine if infective endocarditis is present

Abdominal findings may include the following:

• Stigmata of chronic alcoholism include caput medusae, ascites, and hepatomegaly; splenomegaly may be detected in patients with cirrhosis

• Diffuse abdominal tenderness in a patient with ascites may indicate spontaneous bacterial peritonitis, but other causes of peritonitis (eg, ruptured appendicitis) can occur as well. Peritoneal findings should not be ascribed to opiate withdrawal, though significant gastrointestinal distress with cramping and vomiting are common

• Rectal examination may indicate evidence of GI bleeding.

• Opiate use suppresses peristalsis and commonly produces chronic constipation. During withdrawal, increased bowel sounds, abdominal cramping, vomiting, and diarrhea can be seen.

Findings in the extremities include the following:

• Examine the limbs and joints for evidence of trauma or joint infection.

• Unexplained painful and limited hip movements in a patient with intravenous drug abuse and fever suggests psoas abscess.

Neurologic examination findings may include the following:

• Alcohol withdrawal results in a progressive sequence of increasing anxiety, agitation, confusion, disorientation, visual and auditory hallucinations, seizures, dysphoria, panic, and potentially violent attacks on others

• Dysphoria due to opioid withdrawal may also promote negative reactions and possible violence in affected patients but are not associated with delirium

• Cranial-nerve deficits may indicate Wernicke encephalopathy (ocular nerve palsies), intracranial trauma, or bleeding

• Ataxia can be seen in Wernicke-Korsakoff syndrome

• Peripheral neuropathy is common in chronic alcoholism, but it is difficult to confirm in a minimally cooperative patient

• Focal neurologic deficits, other than those listed above, meningeal signs, and coma are not a part of the clinical picture of alcohol withdrawal and require further investigation

Skin findings may include the following:

• Spider angiomas, gynecomastia, and sparse pubic hair are common in persons with chronic alcoholism

• Patients with intravenous drug abuse have evidence of injections, such as tract marks, and they often have tattoos to mask these marks

• Piloerection is common during opioid withdrawal