Is Hemodialysis Useful in Barbiturate Poisoning? A Clinical Review

With appropriate supportive care, the in-hospital mortality rate for barbiturate toxicity is under 2% [1.5.4]. In severe cases, particularly with long-acting barbiturates, the question arises: is hemodialysis useful in barbiturate poisoning? This intervention can be critical for accelerating drug elimination.

Quick Summary

Hemodialysis is a highly effective treatment for severe barbiturate poisoning, especially for long-acting agents like phenobarbital. It accelerates drug clearance, reduces coma duration, and is preferred in specific clinical situations.

Key Points

• Supportive Care is Primary: The initial and most crucial treatment for barbiturate overdose is supportive care, focusing on airway, breathing, and circulation [1.3.3].

• Effectiveness Varies by Drug Type: Hemodialysis is highly effective for long-acting barbiturates (like phenobarbital) but its role is less clear for short-acting ones [1.8.1, 1.2.5].

• EXTRIP Recommends HD: The EXTRIP workgroup recommends intermittent hemodialysis as the preferred extracorporeal treatment in severe long-acting barbiturate poisoning [1.8.3].

• Specific Indications Apply: Hemodialysis is reserved for severe cases with prolonged coma, respiratory depression requiring ventilation, shock, or persistently high drug levels [1.4.6].

• Reduces Coma and ICU Stay: Clinical evidence shows hemodialysis significantly shortens the duration of coma and the length of stay in the intensive care unit [1.2.4].

• High-Flux HD is Superior: Modern high-flux hemodialysis provides better clearance rates than older dialysis methods and can be more effective than hemoperfusion [1.2.3].

• Alternatives Exist: Multiple-dose activated charcoal (MDAC) and alkaline diuresis are other options, but hemodialysis offers superior clearance in severe cases [1.7.3, 1.4.6].

The Evolving Landscape of Barbiturate Poisoning

Barbiturates, a class of drugs derived from barbituric acid, act as central nervous system depressants. Historically, they were widely prescribed for anxiety, insomnia, and seizure disorders [1.3.4]. However, their use has significantly declined due to a narrow therapeutic index—the small margin between a therapeutic dose and a toxic one [1.5.1]. During their peak use from 1957 to 1963, New York City alone recorded 8,469 cases of barbiturate poisoning [1.5.5]. While prescriptions have fallen dramatically, from over 24 million in 1968 to around 2.1 million in 2019 in the U.S., severe poisoning still occurs and represents a serious medical emergency [1.5.1]. The primary dangers of overdose are profound respiratory depression, coma, and hemodynamic instability, which can lead to death [1.5.3, 1.4.6]. Management has evolved, with supportive care being the cornerstone of treatment. However, in severe cases, more aggressive interventions are needed to remove the toxin from the body.

Understanding the Management of Barbiturate Overdose

The standard treatment for barbiturate overdose begins with immediate supportive care. This includes securing the patient's airway, providing mechanical ventilation if necessary to combat respiratory depression, and administering IV fluids to maintain blood pressure and circulation [1.3.3, 1.3.2]. Another common intervention is the administration of multiple-dose activated charcoal (MDAC), which binds to the barbiturates in the gastrointestinal tract, preventing further absorption [1.3.6]. For certain barbiturates, urinary alkalinization can enhance renal excretion [1.7.6].

However, when these measures are insufficient, or when a patient presents with life-threatening toxicity, clinicians consider extracorporeal treatments (ECTR). The central question in these critical scenarios is: is hemodialysis useful in barbiturate poisoning? The answer depends significantly on the specific type of barbiturate ingested.

The Role of Hemodialysis and its Effectiveness

Hemodialysis is a procedure that removes waste products and toxins from the blood when the kidneys are unable to do so. It works by circulating the patient's blood through a special filter, called a dialyzer or artificial kidney [1.4.5]. The effectiveness of hemodialysis for removing a specific drug is determined by several factors, including the drug's molecular weight, water solubility, volume of distribution (Vd), and degree of protein binding [1.4.5].

• Long-Acting Barbiturates (e.g., Phenobarbital): These drugs are considered highly dialyzable [1.8.1, 1.8.3]. Phenobarbital has a low volume of distribution, low lipid solubility, and moderate protein binding (40-60%), which are characteristics that make it amenable to removal by hemodialysis [1.8.2, 1.4.5]. Modern high-flux, high-efficiency hemodialysis has been shown to be exceptionally effective, with clearance rates that can surpass older dialysis methods and even charcoal hemoperfusion, another ECTR method [1.2.3, 1.6.1]. Studies show that hemodialysis can dramatically reduce the half-life of phenobarbital, leading to rapid decreases in blood levels and significant clinical improvement [1.2.4, 1.2.2].

• Short-Acting Barbiturates (e.g., Pentobarbital, Secobarbital): The role of hemodialysis for short-acting barbiturates is more controversial [1.2.5]. These drugs have a larger volume of distribution and higher protein binding, which theoretically makes them less effectively removed by dialysis [1.2.5]. However, the Extracorporeal Treatments in Poisoning (EXTRIP) workgroup classifies them as "moderately dialyzable" [1.8.3]. In cases of massive overdose leading to severe, refractory hypotension or prolonged coma, hemodialysis has been used successfully to enhance clearance and shorten the duration of intensive care unit (ICU) stay [1.2.5].

Clinical Indications for Hemodialysis

The EXTRIP workgroup, a global authority on poisoning treatment, recommends restricting ECTR, with intermittent hemodialysis as the preferred method, to cases of severe long-acting barbiturate poisoning [1.4.2, 1.8.3].

The specific indications for initiating hemodialysis include:

1. Prolonged Coma: To reduce the length of unconsciousness and associated complications.
2. Respiratory Depression: Especially when it necessitates mechanical ventilation [1.4.6].
3. Shock: When blood pressure remains dangerously low despite fluid resuscitation.
4. Persistent or Worsening Toxicity: If the patient's condition does not improve or deteriorates despite supportive care and MDAC [1.8.3].
5. Persistently Elevated Drug Levels: When serum barbiturate concentrations remain dangerously high [1.8.3].

Hemodialysis is generally continued until there is clear clinical improvement, such as the patient regaining consciousness or being weaned from mechanical ventilation [1.4.6, 1.2.4].

Comparison of Treatment Modalities

Treatment Modality	Description	Primary Use Case in Barbiturate Poisoning	Advantages	Disadvantages
Supportive Care	Management of airway, breathing, and circulation (ABCs); IV fluids, vasopressors [1.3.3].	Cornerstone of treatment for all cases of barbiturate poisoning.	Non-invasive; sufficient for most mild to moderate cases [1.6.2].	May be insufficient for severe toxicity; does not actively remove the drug.
Activated Charcoal (MDAC)	Oral administration to bind the drug in the GI tract, preventing absorption [1.3.6].	Used in conjunction with supportive care, especially for recent ingestions.	Non-invasive; effective at reducing drug absorption.	Less effective if presentation is delayed; risk of aspiration in obtunded patients.
Alkaline Diuresis	IV sodium bicarbonate to raise urine pH (>7.5) and promote drug excretion [1.7.3].	Primarily for long-acting barbiturates like phenobarbital [1.7.6].	Can enhance renal elimination.	Inferior to MDAC and hemodialysis [1.7.3]; risk of fluid overload and electrolyte imbalance.
Hemodialysis	Extracorporeal blood filtration to actively remove the drug from circulation [1.4.5].	Severe poisoning with long-acting barbiturates (e.g., phenobarbital) meeting specific criteria [1.8.3].	Highly effective drug clearance; shortens coma and ICU stay; widely available [1.2.4, 1.4.5].	Invasive; requires specialized equipment and personnel; potential for complications.

Conclusion

So, is hemodialysis useful in barbiturate poisoning? The answer is a definitive yes, but with important qualifications. For severe poisoning with long-acting barbiturates like phenobarbital, hemodialysis is not just useful—it is a life-saving intervention recommended by experts [1.4.6]. It significantly accelerates drug elimination, shortens the duration of coma and mechanical ventilation, and can be crucial for patients who fail to improve with standard supportive care [1.2.4, 1.2.3]. While its role in short-acting barbiturate overdose is less defined, it may be considered in life-threatening situations [1.2.5]. The decision to initiate hemodialysis rests on a careful evaluation of the specific barbiturate involved, the severity of the clinical presentation, and the patient's response to initial conservative management.

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For further reading, the EXTRIP workgroup provides detailed recommendations on this topic: Extracorporeal Treatment for Barbiturate Poisoning: Recommendations from the EXTRIP Workgroup

Frequently Asked Questions

What is the first thing to do for a suspected barbiturate overdose?

The first and most important step is to call for emergency medical help immediately (e.g., 911). Then, ensure the person's airway is clear and monitor their breathing while waiting for assistance [1.3.2, 1.3.3].

Is hemodialysis always used for barbiturate poisoning?

No. It is reserved for severe cases, primarily involving long-acting barbiturates like phenobarbital, where the patient has a prolonged coma, shock, or respiratory failure despite supportive care [1.8.3, 1.4.6].

Why is hemodialysis more effective for phenobarbital than other barbiturates?

Phenobarbital is a long-acting barbiturate with properties that make it 'dialyzable': low lipid solubility, a small volume of distribution, and moderate protein binding. Short-acting barbiturates are more lipid-soluble and have higher protein binding, making them harder to remove via dialysis [1.8.2, 1.4.5].

What is the difference between hemodialysis and charcoal hemoperfusion?

Hemodialysis filters toxins from the blood using a semipermeable membrane (dialyzer). Hemoperfusion passes blood over a cartridge containing an adsorbent material like charcoal to bind toxins directly. While hemoperfusion was once favored for protein-bound drugs, modern high-efficiency hemodialysis is now often preferred for phenobarbital poisoning due to its high clearance rates and wider availability [1.4.5, 1.2.3].

Can activated charcoal treat barbiturate poisoning?

Yes, multiple doses of activated charcoal (MDAC) are a standard treatment. It works by binding to the barbiturates within the gut, preventing them from being absorbed into the bloodstream. It is often used alongside other supportive treatments [1.3.6].

What is alkaline diuresis and is it effective?

Alkaline diuresis involves administering intravenous sodium bicarbonate to make the urine more alkaline (pH ≥ 7.5), which can help the kidneys excrete certain drugs like phenobarbital. However, it is considered less effective than multiple-dose activated charcoal or hemodialysis for severe poisoning [1.7.3, 1.7.6].

How do doctors decide when to stop hemodialysis?

The decision to stop hemodialysis is based on the patient's clinical improvement. This typically includes signs like regaining consciousness, improved respiratory function (ability to be weaned from a ventilator), and stable vital signs [1.4.6].