Failure of pentobarbital to reduce cerebral oxygen consumption in rats after non-haemorrhagic closed head injury

Abstract

Different studies have advocated the use of barbiturates 4,1 in neurotrauma while others have presented contradictive data 7,9. The recent meta-analysis published by 6 shows a dramatic lack of effect with 68% of unresponsive patients and a 25% chance of inducing a blood pressure drop. Via a currently not completely understood mechanism, barbiturates depress cerebral oxygen consumption and cause a secondary decrease in cerebral blood flow. This vasoconstrictive action results in a decreased cerebral blood volume in the arterial compartment which consequently decreases ICP 2,8,3,5. Since it is unknown whether barbiturates suppress cerebral oxygen metabolism early after cerebral trauma, we evaluated the influence of pentobarbital on cerebral oxygen handling of normal rats and rats subjected to non-haemorrhagic closed head injury (CHI). Our multi-wavelength near infrared spectroscopy (NIRS)-system, developed at the University College London, can be used for the assessment of concentrations of oxyhaemoglobin, deoxyhaemoglobin and oxidised cytochrome oxidase in the brain in toto. Oxygen delivery was assessed by measuring cerebral perfusion and oxygen extraction, enabling the calculation of cerebral metabolic rate of oxygen (CMRO2). Mitochondrial function was assessed by studying changes in the oxidised cytochrome oxidase concentration. CHI causes changes in both systemic and cerebral haemodynamics. Cerebral blood flow was reduced to 66% of the control value but the cerebral metabolic rate of oxygen remained unchanged. Pentobarbital administration induced a significant lowering of the cerebral oxygen consumption in normal rats associated with a secondary decrease in cerebral perfusion. In rats subjected to CHI, pentobarbital was unable to lower the cerebral metabolic demand and did not cause a decrease in perfusion. Pentobarbital was unable to significantly modulate mitochondrial function, as assessed by the change in oxydised cytochrome oxidase signal, in traumatised rats whereas it exerted this effect in all control animals. The oxidised cytochrome oxidase signal, although unaltered when considering the whole group, clearly shows that we have 4 irresponsive animals and 2 responsive animals. Only 2 of 6 animals show the hyperoxidation of cytochrome oxidase after administration of the pentobarbital, a feature found in every pentobarbital treated control. This proportion, although a crude estimate, is in accordance with the findings mentioned above. We therefore conclude that pentobarbital is unable to perform its beneficial effects on the cerebral metabolic in 2 out of 6 rats subjected to CHI.