Lectures on Barbiturate sedative Poisoning

2021-08-08 06:34 PM

Slow-acting barbiturates are glomerular filtered and reabsorbed in the proximal tubule. If urine pH is more alkaline than Barbiturate, it will reduce Barbiturate reabsorption

Outline

The first hypnotic derivative of barbituric acid was Barbital (Veronal) synthesized in 1903 by Eischer and Von Mehring. Since then, dozens of barbiturates have been born. Barbiturates are weak acids.

Classification of Barbiturates

There are two main types: Oxybarbiturate and Thiobarbiturate.

The typical oxybarbiturate is Phenobarbital which is slow acting (3-6 hours).

Thiobarbiturate has a very rapid effect immediately after injection, used for intravenous anesthesia (Thiopental).

Barbiturate metabolism in the body

Barbiturates are easily absorbed in an acidic environment, so they are rapidly absorbed through the gastric mucosa.

Fast-acting barbiturate is easier to dissolve in fat than slow barbiturate, so after 30 minutes of injection, it leaves the brain tissue and enters the fat tissue, so the patient wakes up.

Barbiturates are metabolized in the liver by enzymes present in hepatocytes. Therefore, people with liver failure are susceptible to poisoning.

Slow-acting barbiturates are glomerular filtered and reabsorbed in the proximal tubule. If the urine pH is more alkaline than barbiturates, the reabsorption of barbiturates will be reduced and elimination is greatest in the urine as intact. Therefore, serum alkalinization and diuresis are a good means of renal elimination of barbiturates.

Barbiturate's toxicity

Barbiturates act on the mitochondria of cells to reduce oxygen consumption, the production of heat and lactic acid. At high doses, barbiturates inhibit the central nervous system. The drug acts on the reticular system and the hypothalamus, causing the awakening system to be inhibited, causing coma

Barbiturates inhibit the vasomotor, respiratory centers, the receptors for blood pH, pCO2, pO2 causing loss of cough reflex.

These effects are temporary and disappear without leaving any sequelae after the drug is eliminated.

Symptoms of acute poisoning

Rapid-acting barbiturate poisoning (Thiopental)

May cause increased reflexes such as spasms of the larynx, pharynx.

The rapid injection can cause apnea.

Expired thiopental can cause sulfhemoglobinemia (methemoglobin-like symptoms), cardiovascular collapse, and acute respiratory failure.

Barbiturate poisoning is slow acting

Comatose:

The degree of coma is proportional to the oral barbiturate dose. However, depending on the individual depends on absorption through the intestine, distribution in the body, and the ability of the liver to metabolize. Coma due to barbiturate poisoning can be divided into 4 levels:

Stage 1: Call out and answer. EEG: Tachycardia and normal Alpha waves. Barbiturate blood concentration 20 mg/liter.

Stage 2: Pinch structure, correct response. EEG: Slow Waves Theta and Denta. Barbiturate blood concentration: 40 mg/liter.

Stage 3: Incorrect reaction pinch configuration. EEG: Large slow-wave, no response to noise and pinching. Barbiturate blood concentration: 80 mg/liter.

Stage 4: The pinching structure is no longer responsive, the tendon reflexes are lost, the patient lies still, wheezing, the cough reflex is lost, swallowing response, pupils are often dilated. Autonomic disorders: Respiratory disorders, respiratory arrest, pulse collapse, high fever or hypothermia. EEG: Very slow waves on a straight-line basis (vegetative nerve paralysis). Barbiturate blood concentration: 100 mg/liter.

Respiratory disorders:

It is a manifestation of autonomic dysfunction, usually at stage 4. There are two possible explanations for this disorder:

Centrally induced alveolar hypoventilation due to barbiturates has a direct CNS depressant effect, especially the respiratory center in the medulla oblongata, leading to a decrease in PaO2 and an increase in PaCO2.

Obstruction of the upper respiratory tract due to a deep coma causes tongue retraction, sputum stagnation, loss of cough reflex, and aspiration of vomit and gastric juices.

These two mechanisms lead to very severe acute respiratory failure, especially in the presence of Mendelson's syndrome, and are often the main cause of death.

Circulatory disorders:

Severe barbiturate poisoning causes shock due to paralysis of the autonomic nerves, which reduces the impulses of the vessel walls, causing hypotension and collapse. Shock is more likely to occur if it is combined with dehydration, pulmonary embolism due to prolonged lying.

Dysregulation of body temperature:

Patients may have a high fever or hypothermia in case of severe poisoning.

Superinfection:

In the respiratory system due to sputum and atelectasis.

In the ulcer due to lying motionless.

Respiratory failure:

Acute functional renal failure due to dehydration or vascular collapse.

Acute renal failure in patients with latent adrenal damage.

Illness occasion:

Barbiturate poisoning is a favorable cause of the cerebrovascular accidents, pulmonary embolism, myocardial infarction.

To solve

Gastric lavage

When patients drink less than 6 hours because after 6 hours Barbiturate only remains 2% in the stomach. Intubation with balloon tamponade followed by gastric lavage to prevent Mendelson's syndrome. Add 5g of sodium bicarbonate per liter of fluid, wash about 3-5 liters, then pump into the stomach 30g of sodium bicarbonate or sorbitol. Pay attention to take gastric juice to look for toxins.

Alkalization - Infusion

Effective in slow-acting barbiturate poisoning but ineffective in short-acting barbiturate poisoning.

Contraindications: Renal failure, heart failure, liver failure.

Infusion: 3 to 5 times a day, each infusion in turn: Sodium bicarbonate 140/00 500ml, Glucose 10% 500ml, Sodium chloride 90/00 500ml, put into each bottle 1.5g Calcichloride.

Intravenous injection: Lasix 20mg, 4-6 times / day (3 days injection).

Monitor CVP, ECG, electrolytes, and urine output to adjust fluid and electrolytes.

Extra-renal dialysis

Effective for both types.

Indications: Renal failure, liver failure, severe toxicity.

Artificial kidney: Very good filtration (50 ml/min purification), after 6 hours, ½ of the barbiturate in the blood is eliminated, the patient wakes up quickly.

Peritoneal dialysis: Dialysis is slower than hemodialysis (8 ml/min) but easy to do and has few complications (24 hours of peritoneal dialysis is equal to 6 hours of hemodialysis).

Respiratory - circulatory resuscitation

Prevention of respiratory failure: Intubation, frequent sputum aspiration, postural drainage (bed foot elevation 200, head tilted to one side, frequent rotation, back-patting), feeding by catheter, antibiotics.

If there is a respiratory failure (slow breathing, shallow breathing): Increase sputum suction, squeeze balloons, or mechanical ventilation.

If there is atelectasis: Tracheostomy, bronchoscopy.

A slight decrease in blood pressure (80 - 90 mmHg): Adjust water and electrolytes, when central venous pressure is above 10 cmH2O Dopamine infusion.

Severe drop in blood pressure (pulse collapse) due to:

Severe barbiturate poisoning, many types: Plasma infusion, Dopamine. When blood pressure rises, hemodialysis or peritoneal dialysis immediately and simultaneously with Dopamine infusion.

Severe infection, pulmonary embolism, dehydration, irreversible shock.

Low molecular heparin injection to prevent pulmonary embolism.

Prognosis

Prognosis is severe if:

High oral dose and multi-drug combination.

Late.

Complications: Apnea, sputum obstruction, electrolyte disturbances, dehydration, atelectasis, pulmonary embolism, Mendelson's syndrome.

Have underlying disease: Kidney, liver, heart.