C/F:	Investigation	Management:
Incoordination Slurring of speech Unconsciousness Respiratory depression Loss of airway reflexes Hypotension metabolic acidosis Hypothermia Hypoglycemia Convulsion	Blood alcohol conc ABG FBC Glucose RFT LFT	Airway protection Breathing– ventilation , oxygen Fluid resuscitation Aggressive behavior: short-acting BDZ eg.  lorazepam (PO or IV) Antipsychotic medication (e.g., olanzapine IM  Hypoglycemia correction Treatment of convulsion: IV BDZ  Thiamine: chronic excess alcohol use Haemodialysis

 

Methanol/Ethylene glycol poisoning

C/F:

 

Common features:  Vomiting, ataxia, drowsiness, dysarthria, nystagmus F/O toxic metabolites: metabolic acidosis, tachypnea; coma, convulsion
Ethylene glycol ophthalmoplegia, CN palsy, hyporeflexia, myoclonus  Renal pain, ATN → renal calcium oxalate precipitation → Hypocalcemia, hypomagnesemia, hypokalemia	Methanol  Headache, delirium, vertigo Visual impairment, photophobia,  optic disc/retinal edema, impaired pupillary reflex, blindness Pancreatitis, abnormal liver function test
Investigation Urea, electrolyte, chloride, bicarbonate Glucose, calcium, magnesium, albumin Plasma osmolality ABG,  AG, OG calculation→ high osmolar gap, high AG metabolic acidosis Ethylene glycol, methanol concentration	Management: Antidote: Fomepizole/ethanol Metabolic acidosis→NaHCo3, 250 ml of 1.26% Convulsion → IV BDZ Ethylene glycol→ correction of hypocalcemia , if severe ECG features or seizure Methanol poisoning→ folinic acid  Haemodialysis/hemodiafiltration  Renal failure Visual loss

SAQ/OSPE. A 45 years old man was admitted to ED after being found collapsed on the street. O/E, GCS 6, pulse 110 bpm regular, BP 80/60 mmHg, RR 26/min, no h/o fever; pupils dilated, light reflexes reduced; hyperaemic disc with blurred margin on fundoscopy. ABG reveals- pH 7.22, PaO2- 91 mmHg, PaC02- 32 mmHg, HCO3 – 14 mmol/L; S. Na- 146 mmol/L, K-3.5 mmol/L, CI-106 mmol/L

 

Ques.1. What is the biochemical diagnosis 

• HAG metabolic acidosis with respiratory alkalosis

 

Ques.2. Mention most possible underlying cause 

• Methanol poisoning.

 

Ques.3. List 6 important investigations 

• B. urea, S. creatinine, Blood glucose
• S calcium / magnesium / albumin
• Plasma osmolarity
• Measurement of ethylene glycol or methanol concentrations 

 

Ques.4. What happens if untreated 

• Blindness, pancreatitis, renal failure, abnormal LFTs, 
• Aspiration pneumonia, arrhythmia, convulsion, coma, death 

 

Ques.5. Mention 6 immediate management options of this patient. (Methanol poisoning)

• Admission into HDU/ICU under MDT
• ABC management:

• • maintain Airway patency
  •  Breathing: High flow O2

• Circulation: IV access and fluid resuscitation

• For hypoglycemia: IV glucose
• Preventive measure for aspiration pneumonia, Bowel / bladder care 
• For metabolic acidosis

• IV NaHCO3 → 250 mL of 1.26% solution (repeated as necessary)

• For convulsion

• IV BDZ

• Correct hypocalcemia ( for ethylene glycol)

• only if severe ECG features or seizures occur, as it may increase calcium oxalate crystal formation

• Antidote

• Fomepizole or ethanol 
• Ethanol(IV/oral )

1. Loading dose: 10% ethanol 7.5 ml/kg IV over 30-60 minutes
2. Maintenance dose: 10% ethanol 1ml/kg/hr (nondrinker), 1.96ml/kg/hr (chr. drinker)

• Continued until methanol/ethylene glycol concentration is undetectable 

 

• • IV folinic acid (methanol): to enhance metabolism of formic acid (toxic metabolite)

• Hemodialysis / hemodiafiltration / RRT: Indications

•  renal failure, visual loss

• Referral to ophthalmologist
• Psychiatric counseling for alcohol withdrawal
• Monitoring & follow up

 

SAQ. Alcohol misuse and dependence

 

Clinical Feature:

• Social problems

• absenteeism from work, unemployment, 
• marital tensions, child abuse, 
• financial difficulties and 
• problems with the law, such as violence and traffic offenses.

• Low mood

• Anxiety

• Alcohol withdrawal syndrome: (D-16)

1. Anxiety, panic, paranoid delusions, visual and auditory hallucinations 
2. Agitation, restlessness, delirium, tremor, tachycardia, ataxia, disorientation, seizures

• Hallucinations

• Wernicke–Korsakoff syndrome:

1. Wernicke’s encephalopathy: delirium, ophthalmoplegia, nystagmus, ataxia (DONA)
2. Korsakoff syndrome: short-term memory deficits leading to confabulation

• Alcohol-related brain damage

• Effects on other organs

 

Investigation:

• CBC- high MCV

• • γ-glutamyl transferase (GGT)

• carbohydrate-deficient transferrin (CDT)

• Elastography/FibroScan

 

Management

• Health education

• Information on harmful effects of alcohol
• Safe level of consumption
• Alter leisure activities or change job to reduce consumption 

• Psychological treatment

• Cognitive-behavioral therapy
• Support group→ Alcoholics Anonymous (AA)

 

• Alcohol withdrawal syndrome– prevention/treatment

• LA BDZ→ Diazepam 20 mg 4 times daily , tapering over 5-7 days 
• DTs: 

1. In ICU
2. high-dose benzodiazepines (e.g. chlordiazepoxide)
3. If not responsive→ propofol

• Antipsychotic medications are not recommended for treatment of alcohol withdrawal symptoms

 

• Wernicke-Korsakoff syndrome: Immediate high dose of  thiamine-

• Parenteral, Pabrinex: 2 vial 3 times daily for 48 hours
• Then, orally, 100 mg 3 times daily 
• No treatment for WKS, once it has arisen.

• Maintenance of Abstinence 

• Acamprosate:

1. 666 mg 3 times daily
2. Reduce craving for alcohol

• Disulfiram

1. 200-400 mg daily 
2. an ALDH inhibitor→ increase acetaldehyde level→ when alcohol is consumed, unpleasant reaction occurs with headache, flushing, nausea

 

• Treatment of depression: Antidepressant
• Alcoholic hallucination

• antipsychotic- chlorpromazine 

 

• For insomnia:

• Reassurance
• It will begin to improve over subsequent weeks. 
• Maintain “sleep hygiene”

1. maintaining consistent schedules for bedtime and awakening, 
2. avoiding exercise or consumption of large meals before bedtime,
3. keeping the bedroom cool, dark, and quiet at night

 

• Depressant sleep medications not recommended

 

SAQ. A 24-year-old university student, hostel dweller is admitted to hospital with H/O 1 episode of seizure 5 hrs back. His roommate said that he vomited around 10 times within the last 2 days & behaved abnormally as he was seeing animals all around. On exam, pulse 130/m, pupil dilated, tremor was present.

 

1. i) Mention your diagnosis with reasoning. 

• Delirium tremens.

• Reasoning: 

• Delirium tremens describes severe alcohol withdrawal syndrome characterized by both delirium (characteristically agitation & visual hallucination) and physiological hyper-arousal (tremor, sweating & tachycardia)
• All these features in a hostel dweller university student indicate towards the Dx of Delirium tremens. 

 

1. ii) How will you manage him at this stage?

Management:

• ABCDE management
• Long acting large doses of BDZ, tailed off over a period of 5-7 days. 
• Pabrinex 2 vials 3 times daily for 48 hrs, then orally 100 mg 3 times daily.
• Antipsychotics. – not recommended 

 

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From harrison

Ethanol

Relatively low doses of alcohol (one or two drinks per day) may have potential beneficial effects of increasing high-density lipoprotein cholesterol and decreasing aggregation of platelets, with a resulting possible decrease in risk for occlusive coronary disease and embolic strokes. Red wine has additional potential health-promoting qualitiesat relatively low doses due to flavinols and related substances. Suchmodest drinking might also decrease the risk for vascular dementiaand, possibly, Alzheimer’s disease. However, any potential healthfuleffects disappear with the regular consumption of three or more drinksper day, and knowledge about the deleterious effects of alcohol canboth help the physician to identify patients with alcohol use disordersand supply them with information that might help motivate changes in behavior. (Harrison)

 

Acute drinking→ down	Chronic drinking	Withdrawal→ Up
stimulated GABA (inhibitory) inhibit glutamate (excitatory) contributes to anticonvulsant, sleep-inducing, antianxiety, and muscle relaxation effects GABA-high, Glutamate(NMDA)-low Dopamine-high→ leads to craving, linked to high cortisol and ACTH Serotini-high nicotinic acetylcholine-high	upregulation of excitatory receptor	decreases in GABA activity upregulation of  excitatory receptor GABA-low, Glutamate-high

 

Neurological:

• Blackout.
• disturbed sleep.
• snoring and sleep apnea-relaxes muscles in the pharynx
• Bad dreams
• headache, thirst, nausea, vomiting, and fatigue the following day, a hangover
• peripheral neuropathy-bilateral limb numbness, tingling, and paresthesias
• degeneration or atrophy-ataxia, nystagmus
• Wernicke’s (ophthalmoparesis, ataxia, and encephalopathy)
• Korsakoff’s syndromes (severe retrograde and anterograde amnesia) →low levels of thiamine,
• Brain atrophy-cognitive problems- ventricular enlargement and widened cortical sulci → MRI and CT scans

 

THE GASTROINTESTINAL SYSTEM

• Esophagitis, gastritis
• Mallory-Weiss lesion, from violent vomiting

 

Pancreas and Liver

• acute pancreatitis
• decreased oxidation of fatty acids→fat accumulation→ alcohol-induced hepatitis, cirrhosis

 

CANCER

• Female- breast cancer
• both sexes –  oral and esophageal cancers 
• many other cancers.

 

HEMATOPOIETIC SYSTEM;

• RBC– MCV- high, due to effects on stem cells; if malnutrition, sideroblastic changes may occur
• folic acid deficiency-hypersegmented neutrophils, reticulocytopenia, hyperplastic bone marrow
• WBC– leukopenia, decrease granulocyte mobility and adherence, and impair delayed-hypersensitivity →  false-negative tuberculin skin test).
• Platelet– thrombocytopenia,

 

CARDIOVASCULAR SYSTEM

• Hypertension.
• increased risk for coronary artery disease- high LDL cholesterol
• Cardiomyopathy→ arrhythmias
• paroxysmal tachycardia after heavy drinking in individuals showing no other evidence of heart disease, a syndrome known as the “holiday heart.”

 

GENITOURINARY SYSTEM CHANGES, SEXUAL FUNCTIONING, AND FETAL DEVELOPMENT

• can increase sexual drive but also decrease erectile capacity in men
• Even in the absence of liver impairment, a significant minority of chronic heavy drinking men show irreversible testicular atrophy with shrinkage of the seminiferous tubules, decreases in ejaculate volume, and a lower sperm count
• Women-  amenorrhea, a decrease in ovarian size, infertility, spontaneous abortion. 
• fetal alcohol syndrome

 

OTHER EFFECTS

• Alcoholic myopathy,
• fractures and osteonecrosis of the femoral head.
• Hormonal changes

• increase in cortisol levels
• inhibition of vasopressin secretion at rising blood alcohol concentrations
• enhanced secretion at falling blood alcohol concentrations→ looks overhydrated

• T3, T4- decreased

Terminology: alcohol use disorder, also called alcoholism or alcohol dependence.

 

Alcohol use disorder

 

Screening tool:

• • standardized questionnaires: Alcohol Use Disorders Identification Test (AUDIT)

 

Investigation:

• γ-glutamyl transferase (GGT) (>35 U) and carbohydrate-deficient transferrin (CDT) → the combination of the two tests is likely to be more accurate than either alone.

 

Treatment:  Acute intoxication→ withdrawal 

 

ACUTE INTOXICATION

 

• Aggressive behavior:

• reassurance, 
• short-acting benzodiazepine such as lorazepam (PO or IV)
• Antipsychotic medication (e.g., olanzapine IM )

• Intervention:

• motivational interviewing, 
• brief interventions→ FRAMES

1. Feedback to the patient; 
2. Responsibility to be taken by the patient;
3. Advice, rather than orders
4. Menus of options
5. Empathy
6. Self-efficacy

 

ALCOHOL WITHDRAWAL

• Features include

• Tremor of the hands (shakes); 
• agitation and anxiety; 
• autonomic nervous system overactivity including an increase in pulse, respiratory rate, sweating, and body temperature; 
• and insomnia.
• withdrawal seizure,
• withdrawal delirium, AKA delirium tremens (DTs), where the withdrawal includes delirium (mental confusion, agitation, and fluctuating levels of consciousness) associated with a tremor and autonomic overactivity (e.g.increases in pulse, blood pressure, and respirations).
• Risk factor for withdrawal seizure and DTs: 

1. Older age, 
2. concomitant medical problems, 
3. misuse of additional drugs,
4. and higher alcohol quantities.

• Management:

• thorough physical examination for evaluation of possible

1. liver impairment, 
2. gastrointestinal bleeding, 
3. cardiac arrhythmias,
4. infection, and g
5. glucose or electrolyte imbalances.

• offer adequate nutrition and oral multiple B vitamins, including 50–100 mg of oral thiamine daily for a week or more. 

 

• Because most patients with alcohol use disorders who enter withdrawal are either normally hydrated or mildly overhydrated, IV fluids should be avoided unless there is a relevant medical problem or significant recent bleeding, vomiting, or diarrhea.

 

• CNS depressant drug to control symptoms and then tapering over 3-5 days

1. longer half-lives benzodiazepines-(e.g.chlordiazepoxide, diazepam)
2. Dose adjustment 
3. Tapering over 5 days

• Management of DTs

1. In ICU
2. high-dose benzodiazepines (e.g., as much as 800 mg/d of chlordiazepoxide)
3. If not responsive→ propofol
4. Antipsychotic medications are not recommended for treatment of alcohol withdrawal symptoms.

 

THE REHABILITATION PHASE

 

• Cognitive-behavioral therapy
• Peer group – Alcoholics Anonymous (AA)
• For insomnia:

• Reassurence
• It will begin to improve over subsequent weeks. 
• Maintain “sleep hygiene”

1. maintaining consistent schedules for bedtime and awakening, 
2. avoiding exercise or consumption of large meals before bedtime,
3. keeping the bedroom cool, dark, and quiet at night

 

• Depressant sleep medications not recommended

 

• opioid antagonist naltrexone- oral/injection-shorten subsequent relapses, By blocking opioid receptors, naltrexone decreases activity in the dopamine-rich ventral tegmental reward system and decreases the feeling of pleasure if alcohol is imbibed.
• Acamprosate– oral, inhibits NMDA receptors
• disulfiram, 

• an ALDH inhibitor. 
• Produces vomiting and autonomic nervous system instability in the presence of alcohol as a result of rapidly rising blood levels of acetaldehyde. 
• This reaction can be dangerous, especially for patients with heart disease, stroke, diabetes mellitus, or hypertension.

 

Manifestations 

 

Neurologic

Patients are often alert on presentation, the period of inebriation having passed. 

They frequently complain of headache and dizziness. 

However, agitation, acute mania, amnesia, a decreased level of consciousness including coma, and seizures may occur.

In a large series, several patients developed a clinical picture resembling subarachnoid hemorrhage, with headache, vomiting, nuchal rigidity, hypertension, and bradycardia.

Putamenal necrosis, cerebral herniation, and cerebellar necrosis have been reported.

Gastrointestinal

Nausea and vomiting are frequently encountered. 

Other manifestations include flank pain, abdominal pain that is often severe, GI hemorrhage, diarrhea, liver function abnormalities, and pancreatitis.

Ophthalmologic

Signs and symptoms may develop 6 hours or more post ingestion but can be delayed 24 hours or more. Their development depends on the duration of elevation of formate concentration. In two large series, all patients presenting with acidemia also had complaints of visual disturbance. Patients who present early, prior to significant metabolism of methanol, may have no ophthalmologic findings. Symptoms, when present, can include blurred vision; photophobia; visual hallucinations, such as misty vision, “skin over the eyes,” “snowstorm,” “dancing spots,” or “flashes”; partial to total visual loss; and, rarely, eye pain. The findings on examination range from normal, despite visual complaints, to conjunctival injection, visual field constriction, sluggish nonreactive pupils, hyperemic optic discs, papilledema, retinal edema and hemorrhages, and decreased to absent vision. Impairment of the pupillary light reflex implies severe poisoning and a worse prognosis. In Benton’s analysis of the Atlanta outbreak, patients with fixed and dilated pupils were more likely to die or to have permanent visual sequelae.

Other

Sinus tachycardia and increased respiratory rate may be present. 

The patient may complain of breathlessness, and Kussmaul respirations occur as a consequence of acidosis.

The blood pressure is usually maintained until the preterminal stage.

Indeed, the presence of a severe metabolic acidosis in the absence of shock or hypoxia should increase the physician’s suspicion that a toxin, such as methanol or ethylene glycol is involved. When hypotension develops, left ventricular dilation and dysfunction may be present and may persist despite correction of serum Ph.

 Sudden respiratory arrest can occur.

Treatment 

 

General

Supportive care, including appropriate airway management GI decontamination via nasogastric suction for large oral ingestions Sodium bicarbonate IV for life-threatening metabolic acidosis Calcium IV for symptomatic hypocalcemia CNS toxicity Seizures: treat with benzodiazepines, Phenobarbital Monitor for increased cerebral pressure

Alcohol Dehydrogenase Inhibitor

Administer either fomepizole or ethanol as soon as toxic alcohol exposure is known or suspected. Ethanol

Cofactors

Administer cofactors until serum levels of toxic alcohol are undetectable and metabolic acidosis has cleared. Folinic acid (leucovorin), 1 mg/kg per dose (maximum 50 mg per dose) IV every 4 hr

Enhanced Elimination

Institute hemodialysis for one or more of the following conditions: A serum ethylene glycol or methanol level of 50 mg/dL or greater, regardless of symptoms or acid-base status; or Ongoing metabolic acidosis or evidence of end-organ damage, regardless of the serum level; or Unexplained metabolic acidosis with an anion or osmol gap when serum ethylene glycol or methanol levels are not readily obtainable and the suspicion of exposure is high