The interaction and pharmacological modulation of the cardiorespiratory responses to primary thoracic blast injury, haemorrhage resuscitation

Abstract

Blast injuries represent a problem for civilian and military populations. The response to thoracic blast injury involves a reflex bradycardia, hypotension and apnoea. Casualties who have suffered a blast injury are likely to receive morphine as an early treatment, and may go on to suffer a haemorrhage, thus requiring fluid resuscitation. Aims of this thesis included determination of the effect of blast injury on the response to haemorrhage and whether these responses or their interaction are modified by morphine, and to compare the cardiovascular effects of early and late resuscitation with different solutions following blast injury and haemorrhage. Early cessation of the blast-induced apnoea is important if the patient is to adequately maintain arterial oxygen tensions and thus prevent the development of tissue hypoxia and a subsequent secondary inflammatory response. Therefore, the final aim of this thesis was to determine whether doxapram could shorten the duration of apnoea induced by thoracic blast. Results confirmed that the response to thoracic blast injury involves a bradycardia, hypotension and apnoea, and also a vasodilation and a reduction in blood flow in the femoral vascular bed. New findings from this thesis show that thoracic blast augments the bradycardia and hypotension seen during haemorrhage and that morphine attenuates this effect. The hypovolaemic blast-injured patient may be resuscitated early or late after haemorrhage with blood, 0.9% saline, colloids (modified gelatin and hydroxyethyl starch) hypertonic saline or hypertonic/hydroxyethyl starch. These fluids restored blood pressure and femoral blood flow to pre-haemorrhage levels for at least 30 minutes. However, resuscitation with hypertonic saline/de>ttran was shown to be deleterious following blast injury and haemorrhage as blood pressure and femoral blood flow was not maintained for longer than 5 minutes following resuscitation with this fluid. The blast-induced apnoea and hypotension can be significantly attenuated by doxapram immediately following blast injury. This respiratory stimulant may also result in an improvement in venfilation/perfusion matching in the lungs and thus better fissue oxygenation, as administration of doxapram resulted in an improvement in the indices of metabolic acidosis. The new information gained from the work covered by this thesis could potentially lead to better treatment of the blast-injured victim.