Can pentobarbital (phenobarbital) induce neurogenic shock?

From the Guidelines

Pentobarbital can potentially induce neurogenic shock, particularly at high doses, due to its vasodilatory and cardiodepressant effects, as evidenced by studies showing a high rate of hypotension requiring pressors in patients treated with intravenous pentobarbital 1.

Key Points to Consider

• Pentobarbital is a barbiturate that acts as a central nervous system depressant by enhancing the inhibitory effects of GABA, leading to significant vasodilation and decreased sympathetic tone.
• The risk of neurogenic shock is higher in patients with pre-existing cardiovascular instability or when pentobarbital is administered rapidly intravenously.
• Clinicians should monitor vital signs closely when administering pentobarbital, especially blood pressure and heart rate, and be prepared to provide vasopressor support if needed.
• Fluid resuscitation may be necessary to maintain adequate blood pressure, and in severe cases, vasopressors like norepinephrine might be required to counteract the vasodilation and maintain tissue perfusion.

Evidence from Recent Studies

• A comprehensive review of the literature by Claassen et al 1 identified 106 patients treated with intravenous pentobarbital, with a treatment success rate of 92%, but also a high rate of hypotension requiring pressors.
• Another study by Stecker et al 1 found that pentobarbital was associated with a longer time to seizure control compared to propofol, but with no significant difference in seizure control rates.

Clinical Implications

• Clinicians should be aware of the potential risks of neurogenic shock associated with pentobarbital administration, particularly in patients with pre-existing cardiovascular instability.
• Close monitoring of vital signs and preparedness to provide vasopressor support are essential when administering pentobarbital.
• The benefits of pentobarbital in treating refractory status epilepticus should be weighed against the potential risks of neurogenic shock, and alternative treatments should be considered when possible.

From the FDA Drug Label

Typical shock syndrome (apnea, circulatory collapse, respiratory arrest, and death) may occur. In extreme overdose, all electrical activity in the brain may cease, in which case a "flat" EEG normally equated with clinical death cannot be accepted. Fluid therapy and other standard treatment for shock, if needed.

Neurogenic shock is not explicitly mentioned in the drug label as a potential effect of pentobarbital. However, hypotension and circulatory collapse are mentioned, which can be related to shock.

• The label does mention shock syndrome, but it is not specified as neurogenic.
• CNS depression is a known effect of pentobarbital, which can lead to various complications, including respiratory depression and cardiovascular collapse. Since the label does not directly address neurogenic shock, no conclusion can be drawn about its potential to be induced by pentobarbital 2.

From the Research

Neurogenic Shock and Pentobarbital

• Neurogenic shock is a condition that can occur after a severe spinal cord injury, which can disrupt the sympathetic nervous system and lead to a loss of vasomotor tone, resulting in hypotension 3, 4.
• Pentobarbital is a barbiturate that can be used to treat refractory intracranial hypertension, but its use can be associated with several complications, including hemodynamic instability and respiratory depression 4, 5.
• There is no direct evidence to suggest that pentobarbital can induce neurogenic shock, but its use can lead to hypotension, which can be a contributing factor to neurogenic shock 6, 7.

Complications of Pentobarbital Use

• High-dose pentobarbital infusion can lead to propylene glycol toxicity, which can cause metabolic acidosis, acute kidney failure, and other complications 4, 7.
• Pentobarbital can also lead to a decrease in cerebral perfusion pressure, which can worsen brain injury and lead to further complications 5, 6.
• The use of pentobarbital requires close monitoring of the patient's hemodynamic status, as well as their renal function and serum osmolality, to prevent complications 7.

Pharmacokinetics of Pentobarbital

• The pharmacokinetics of pentobarbital can vary depending on the patient's condition, with a mean clearance of 0.72 ml/min/kg and a volume of distribution of 1.03 L/kg in patients with severe head injury 3.
• The terminal half-life of pentobarbital can range from 15.6 to 22.3 hours, depending on the patient's condition and the dose administered 3, 6.
• The use of high-dose pentobarbital infusion requires careful monitoring of the patient's serum concentrations to prevent toxicity and ensure effective treatment 3, 6.