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Title: Experimental studies of resuscitation following hypovolaemia in an animal model
Author: Stapley, Sarah Ann
ISNI:       0000 0001 3477 845X
Awarding Body: University of Southampton
Current Institution: University of Southampton
Date of Award: 2004
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Whilst an artificial haemoglobin substitute remains elusive resuscitation of the trauma casualty is still a subject for debate. This study aims to develop a defined and reproducible model of uncontrolled intra-abdominal haemorrhage in the large white pig, use the model to evaluate the potential of repeated dosing of HSD and examine the use of intraosseous infusion (IO) as a method of administration for resuscitation fluids. 36 instrumented terminally anaesthetised female pigs (weight range 39-82kg) were divided into four groups following an uncontrolled haemorrhage insult sustained by causing intra-abdominal common iliac artery bleeding. Group 1, the controls, received no treatment. Group 2 received intravenous (IV) HSD at 1 h and 4 h post insult. Group 3 received IV HSD at 1 h and 7 h post insult. Group 4 received HSD at 1h and 4 h post insult via IO infusion. Physiological and biochemical parameters were measured up to 12 h post insult, dependent on survival. Attempts were made to determine blood volume loss from the animal model using radioactive isotope labelling. Post mortem examination was undertaken on all experimental animals. All studies were authorised under the Animals (Scientific Procedures) Act 1986. The initial insult produced a fall in mean arterial blood pressure (MABP) of greater than 40% (range 42-66%) and in cardiac index (CI) of 43% (range 19-84%). Both values significant P < 0.0001 Mann Whitney U. All animals showed a subsequent recovery in cardiovascular parameters towards more normal values, however MABP and CI remained significantly lower at 1h post insult. Infusion of HSD caused a significant hypernatraemia and diuresis particularly following the 2nd dose in all treated groups, although increases in cardiovascular parameters remained non significant when treated groups were compared with the control group. Overall survival showed no difference using the Peto and Peto rank test. Blood volume calculations using Chromium 51 red blood cell labelling techniques showed volume changes between 16 to 60% with consistency and accuracy being difficult to maintain. This study has developed a survivable model of uncontrolled intra-abdominal haemorrhage insult, which repeatedly produced significant reductions in cardiovascular parameters. This model has been used to evaluate the use of HSD as a resuscitation regimen. HSD was demonstrated to rapidly improve cardiovascular parameters to more normal levels either via IV or IO routes. However, the increase in MABP was detrimental to some animals causing rebleeding and early death. In addition the metabolic sequelae observed post infusion were found to be potentially detrimental to survival. From an assessment of the studies in this thesis the author is unable to recommend the use of repeat dosing of HSD in the treatment of uncontrolled intra-abdominal haemorrhage.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available