Barbiturate coma may promote reversible bone marrow suppression in patients with severe isolated traumatic brain injury.
OBJECTIVE
Barbiturate coma is employed in brain-injured patients whenever increases in intracranial pressure remain unresponsive to less aggressive therapeutic regimens. Barbiturate-mediated neuroprotection, however, is weakened by an increased infection rate related to barbiturate-induced immunosuppression. Co-administration of barbiturates with antibiotics known to induce bone marrow suppression could, in turn, potentiate barbiturate-mediated immunosuppression. Adverse drug reactions and interactions of thiopental with antibiotics in terms of leukopenia, infection rate, and bone marrow suppression were investigated.


METHODS
White blood cells were measured daily, tracheobronchial secretion and urine were examined for bacterial growth twice a week or if an infection was suspected.


RESULTS
A total of 52 patients with severe isolated head injury were consecutively investigated. Due to increased intracranial pressure (ICP), which did not respond to analgosedation, barbiturate coma was performed in 23 cases. The other 29 patients remained analgosedated. Leukocytes and neutrophils were reversibly and significantly decreased in all patients, mostly sustained under thiopental. The pulmonary infection rate due to gram-negative organisms was nearly doubled during barbiturate coma. Reversible agranulocytosis and bone marrow suppression attributed to antibiotics developed in six patients after thiopental administration. Mortality rate, however, was not increased by these adverse effects.


CONCLUSIONS
Barbiturate coma may cause reversible leukopenia and an increased infection rate. Long-term administration of thiopental may also promote reversible antibiotic-induced bone marrow suppression. The mechanisms and site of interaction between thiopental and antibiotics cannot be assessed by the present study and remain to be clarified. However, during and after barbiturate coma, close monitoring of leukocytes and infections and careful selection of antibiotics is required.
Stover
J F
JF
Division of Trauma Surgery, Zürich University Hospital, Switzerland.
Stocker
R
R
D000328:Adult; D000368:Aged; D000380:Agranulocytosis / Q000139:chemically induced; D019883:Alkyl and Aryl Transferases / Q000378:metabolism; D000900:Anti-Bacterial Agents / Q000009:adverse effects / Q000627:therapeutic use; D001853:Bone Marrow / Q000187:drug effects* / Q000276:immunology; D001930:Brain Injuries / Q000188:drug therapy* / Q000276:immunology*; D003128:Coma / Q000139:chemically induced / Q000276:immunology*; D003422:Critical Care; D005260:Female; D016905:Gram-Negative Bacterial Infections / Q000188:drug therapy / Q000209:etiology; D006801:Humans; D006993:Hypnotics and Sedatives / Q000009:adverse effects* / Q000627:therapeutic use; D007165:Immunosuppression Therapy; D007970:Leukopenia / Q000139:chemically induced; D008171:Lung Diseases / Q000188:drug therapy / Q000209:etiology; D008297:Male; D008875:Middle Aged; D008930:Mitochondria, Liver / Q000187:drug effects / Q000201:enzymology; D009504:Neutrophils / Q000187:drug effects / Q000502:physiology; D011446:Prospective Studies; D013874:Thiopental / Q000009:adverse effects* / Q000627:therapeutic use
D000900:Anti-Bacterial Agents; D006993:Hypnotics and Sedatives; D019883:Alkyl and Aryl Transferases; C112459:geranylpyrophosphate olivetolate geranyltransferase; D013874:Thiopental