Lactic Acidosis Overview

Lactic Acidosis

• Lactic acidosis is a condition where there is an accumulation of lactic acid in the blood, causing a decrease in blood pH.
• Pyruvate combines with NADH to generate lactate, mainly in skeletal muscles.
• Lactate is continuously generated and consumed, with an increase in generation during exercise and seizures.
• Mechanisms of Lactic Acidosis:
• Most Common: Tissue hypoxia, due to decreased oxygen delivery or microcirculation issues.
• Less Common: Stimulation of beta-2 receptors by drugs like epinephrine or albuterol.
• Impaired oxidative phosphorylation: Caused by medications like antiretrovirals, metformin, and propofol.
• Impaired pyruvate dehydrogenase activity: Caused by thiamine deficiency.
• Diagnosis:
• Increased anion gap is a clue.
• Normal anion gap can occur in about half of cases with high lactate levels.
• Lactate levels can be measured in arterial or venous blood.
• Higher lactate levels are associated with a worse prognosis.
• Management:
• Primarily involves treating the underlying cause.
• Sodium bicarbonate may be used if pH is less than 7.2, but this is controversial.
• Dialysis is a controversial treatment option for severe cases.

Hyponatremia

• Hyponatremia is defined as a serum sodium level below 136 mmol/L.
• The first step in managing hyponatremia is to differentiate between hypotonic and hypertonic hyponatremia.
• Hypotonic Hyponatremia:
• Pseudo hyponatremia: A laboratory artifact due to high protein, triglyceride, or cholesterol levels.
• Can also be caused by hyperglycemia, mannitol, and hypertonic radiocontrast.
• Important Considerations:
• Assess hyponatremia severity as acute (less than 48 hours) or chronic.
• Consider if the hyponatremia is symptomatic or asymptomatic.
• Determine if the hyponatremia is hypovolemic, euvolemic, or hypervolemic.

Hyponatremia (additional causes)

• Hyponatremia is most commonly caused by diuretics, polydipsia, and water intoxication.
• Other causes include dehydration, heart failure, and medications like haloperidol, diuretics, and others.

Managing Hyponatremia

• Determine if hyponatremia is symptomatic.
• If symptomatic, treat immediately with hypertonic saline, being careful not to overcorrect.
• Obtain urine osmolality. A low urine osmolality (less than 100) suggests polydipsia or beer potomania.
• Obtain urine sodium. A low urine sodium indicates decreased effective volume to the kidneys.
• A high urine sodium suggests SIADH, adrenal insufficiency, hypothyroidism, or other conditions.

Treatment of Hyponatremia

• Treatment depends on the cause and severity.
• Acute hyponatremia: Treat with hypertonic saline bolus, followed by continuous infusion if necessary.
• Chronic hyponatremia: Fluid restriction for SIADH, normal saline or lactated ringers for hypovolemic hyponatremia, and fluid restriction for hypervolemic hyponatremia.

Overcorrection of Hyponatremia

• Rapid correction of chronic hyponatremia or rapid onset of acute hyponatremia can lead to osmotic demyelination syndrome.
• Risk factors for demyelination syndrome include low baseline sodium, hypokalemia, alcoholism, malnutrition, and liver disease.
• Aim for a correction no more than 8 mEq/L per day.

Hypernatremia

• Hypernatremia is characterized by increased serum sodium concentration due to water loss or hypertonic sodium gain.
• Water loss can be caused by diabetes insipidus, insensible losses, or hypotonic fluid loss.
• Hypernatremia typically occurs in patients with impaired thirst mechanism, such as infants, elderly individuals, and those with altered mental status.

Managing Hypernatremia

• Address the underlying cause of hypernatremia.
• Correct hypernatremia gradually, aiming for a fall in serum sodium concentration no more than 0.5 mEq/L per hour.
• Preferred route of correction is oral hydration; if IV solution is required, use hypotonic fluids.

Drug Poisoning

• Drug overdose deaths are a significant public health issue, with fentanyl being the most common cause.
• Different drug toxicities present with distinctive signs and symptoms.

Toxic Syndromes

• Anticholinergic toxic syndrome: Dilated pupils, dry mucous membranes, altered mental status.
• Cholinergic toxic syndrome: Diarrhea, diaphoresis, bradycardia, constricted pupils, bronchorrhea.
• Opioid toxic syndrome: Constricted pupils, depressed respiratory drive.
• Sympathomimetic toxic syndrome: Dilated pupils, tachycardia, hypertension.

Osmolar Gap

• An elevated osmolar gap suggests the presence of an unmeasured osmotic substance, often an alcohol like ethanol, propanol, methanol, or ethylene glycol.

QT Interval Prolongation

• Certain drugs can block the potassium efflux, prolonging the QT interval.
• These drugs include antihistamines, antipsychotics, some antibiotics (e.g., azithromycin, clarithromycin), antiarrhythmics, macrolides, and methadone.
• Maintaining normal electrolytes, especially magnesium, is important in patients with QT prolongation.

Drugs Blocking Fast Sodium Channels

• Tricyclic antidepressants, carbamazepine, class 1 & 3 antiarrhythmics, cocaine, phenothiazines, propranolol, verapamil, and others can block fast sodium channels.
• Blockage can lead to sine wave pattern on EKG or ventricular tachycardia.
• Treatment includes sodium bicarbonate.

Serotonin Syndrome

• Serotonin syndrome is typically caused by drug interactions, such as SSRIs with MAOIs, tramadol, or meperidine.
• Symptoms include high temperature, altered mental status, rigidity, hyperreflexia, and clonus.
• Treatment focuses on supportive care and may include cyproheptadine.

Neuroleptic Malignant Syndrome

• Neuroleptic malignant syndrome is typically caused by antipsychotics but can also be caused by dopamine agonists.
• Symptoms are similar to serotonin syndrome but with less hyperreflexia, including high fever, altered mental status, rigidity, autonomic instability, and elevated CPK.
• Treatment includes bromocriptine and dantrolene.

Malignant Hyperthermia

• Malignant hyperthermia is a genetically determined reaction to depolarizing neuromuscular blocking agents or volatile general anesthetics.
• Treatment focuses on removing the inciting agents, providing supportive care, and potentially dantrolene.

Antidotes

• Acetaminophen toxicity: N-acetylcysteine
• Beta blocker toxicity: Glucagon, calcium, vasopressors, insulin plus glucose, lipid emulsion therapy
• Calcium channel blocker toxicity: Calcium, glucagon, insulin plus glucose, lipid emulsion therapy
• Opioid toxicity: Naloxone
• Methanol and ethylene glycol toxicity: Dialysis
• Cyanide toxicity: Hydroxocobalamin (most effective), other treatments including nitrates and sodium thiosulfate
• Carbon monoxide toxicity: High-flow oxygen

Carbon Monoxide Toxicity

• Carbon monoxide toxicity is typically caused by smoking, malfunctioning heating systems, or poorly ventilated motor vehicles.
• Carbon monoxide binds to hemoglobin, reducing oxygen-carrying capacity and impairing oxygen delivery.
• Diagnosis involves measuring carboxyhemoglobin levels using a co-oximeter.
• Treatment involves high-flow oxygen; hyperbaric oxygen therapy may be necessary in severe cases.

Methemoglobinemia

• Methemoglobinemia is a condition in which ferrous iron in hemoglobin is oxidized to ferric iron, rendering it unable to bind oxygen.
• Congenital forms are caused by deficiencies in cytochrome b5 reductase or NADH-methemoglobin reductase.
• Acquired forms can be caused by medications, chemicals, and certain foods.
• Symptoms include cyanosis, hypoxemia, and discoloration of blood.
• Diagnosis involves measuring methemoglobin levels using a co-oximeter.
• Treatment includes methylene blue or ascorbic acid.

Hypothermia

• Hypothermia is defined as a core body temperature below 35°C.
• Mild hypothermia: 32-35°C
• Moderate hypothermia: 25-32°C
• Severe hypothermia: below 25°C
• Symptoms include shivering, tachypnea, tachycardia, bradycardia, hypoventilation, hyperreflexia, altered mental status, and potential cardiac arrhythmias.
• Treatment depends on the severity of hypothermia and may include passive external rewarming, active external rewarming, or invasive techniques.
• It is crucial to rule out other potential causes like infection, sepsis, or hypothyroidism.