Thiopental‐Induced Neutropenia in Two Patients with Severe Head Trauma

Abstract

Thiopental has been used for decades in the treatment of refractory intracranial hypertension in patients with traumatic and nontraumatic head injuries. Commonly reported adverse effects include hypotension, hypokalemia, respiratory complications, and hepatic dysfunction. Neutropenia has rarely been reported as an adverse effect of thiopental. We witnessed probable thiopental-induced neutropenia in two patients with traumatic brain injuries who developed increased intracranial hypertension that was refractory to standard therapy. Based on a MEDLINE search of published case reports and literature, we propose two mechanisms by which thiopental-related neutropenia might be explained. The first is inhibition of inflammatory mediator nuclear factor-kappa B (NF-kappa B), leading to granulocyte apoptosis. The second mechanism involves inhibition of calcineurin. Although the precise link between these two mechanisms has not been elucidated, calcineurin is known to regulate NF-kappa B activity. Development of neutropenia does not appear to be correlated with time but may correlate with plasma concentrations of thiopental. The optimum management of drug-induced neutropenia is unclear. The decision to discontinue thiopental in patients who develop neutropenia should be made by weighing the risks versus benefits. Broad-spectrum antibiotics may be required in the presence of fever. The role of hematopoietic growth factors such as granulocyte colony-stimulating factor is not yet defined. Given the adverse infectious consequences of neutropenia, it is essential to closely monitor neutrophil counts in patients receiving thiopental.

Neutrophil extracellular traps exacerbate neurological deficits after traumatic brain injury

“…Functionally, neutrophil activation induced microcirculatory dysfunction, cerebral hypoperfusion, and edema formation in experimental models of TBI (10,11). Moreover, thiopental, a barbiturate used to manage refractory ICP, was associated with induced neutropenia in patients with TBI (12). Despite the deleterious effect of acute neutrophil activation, the potential benefits of global neutrophil depletion strategies are outweighed by a heightened infection risk in critically ill patients.…”

Decrease in white blood cell counts after thiopentone barbiturate therapy for refractory intracranial hypertension: A common complication

“…Frenette published a case report on two patients with traumatic brain injury who developed neutropenia of 0.1 × 10 9 /L and 0.8 × 10 9 /L after induction of thiopentone barbiturate coma. [5] In another case series of 23 head injured patients receiving thiopentone barbiturate coma for refractory intracranial hypertension, all developed a decrease in WBC counts and 6 developed neutropenia. Four of these patients received bone marrow biopsy, with two showing complete marrow suppression with absent differentiation and another showing partial bone marrow suppression with intact differentiation between reduced neutropoesis.…”

“…[1] While potentially useful in reducing intracranial pressure, multiple adverse effects such as hypotension and hypokalaemia have been reported. [2,3] Leucopenia following administration of thiopentone barbiturate coma has been reported, [4,5] with increased infections attributed to pharmacological immunosuppression by thiopentone. To define the incidence and characteristics of changes in white blood cell counts after induction of thiopentone barbiturate therapy, we performed a retrospective review of patients who received thiopentone barbiturate therapy for refractory intracranial hypertension in our neurosurgical ICU.…”

Immunomodulators in anesthesia

“…However, when administered either over prolonged periods or in higher doses, thiopental may cause iatrogenic immunosuppression. For instance, leucopenia following thiopental-induced coma has been reported in patients with severe head trauma [33,34], and the incidence of infection in patients with brain edema who received longstanding thiopental infusion was higher and seemed dose-dependent [3,35]. Induction of thiopental therapy for refractory intracranial hypertension was also associated with a decrease in leukocytes [36].…”