EXPERIMENTAL PAPERHaemodynamic response to acute hypovolaemia, rapid blood volume expansion and adrenaline administration in an infant animal model☆
Introduction
Hypovolaemia-induced by sudden blood loss triggers a haemodynamic response to maintain perfusion of the vital organs, with vasoconstriction of the skin and other organs.1 The haemodynamic response to acute hypovolaemia and to blood volume expansion has been studied mainly in adults,1, 2 with few studies among children and infant animal models.3, 4, 5
The factors used most commonly to assess hypovolaemic shock and response to treatment are blood pressure, heart rate, central venous pressure and tissue perfusion. However, heart rate can be decreased paradoxically in severe hypovolaemia,6 and blood pressure may be normal even in patients with severe shock.7 Central venous pressure (CVP) and pulmonary capillary pressure (PCP) indicate the effect of blood volume on pressure, though the latter may be altered in patients with ventricular dysfunction or elevated intrathoracic pressures (e.g., in mechanical ventilation with an elevated mean airway pressure). Several studies have found that the intrathoracic blood volume index (ITBI) and global end-diastolic volume index (GEDVI) estimated by femoral arterial thermodilution are better indicators of blood volume than CVP or PCP,3, 8 but few studies have analyzed the evolution of these variables in the case of sudden hypovolaemia and rapid expansion in children.3, 4
International guidelines on the treatment of shock in children recommend administering a fast bolus of 20 mL/kg of isotonic crystalloid when the peripheral perfusion is inadequate even if the blood pressure is normal, and repeating with a second bolus of 20 mL/kg when the heart rate, level of consciousness and capillary filling do not improve.6 Some human and experimental studies have reported that rapid volume expansion can increase the risk of bleeding and worsen the prognosis of patients in haemorrhagic shock.9 However, other studies have not supported these results.10, 11 It has also been suggested that very rapid volume expansion combined with the administration of vasopressors that increase pulmonary arterial pressure can induce or increase pulmonary edema.12
The purposes of this study were: first, to assess the haemodynamic response to acute hypovolaemia, rapid expansion and adrenaline administration in an experimental infant animal model by studying the changes in blood volume and extravascular lung water as measured by femoral arterial thermodilution; and second, to assess the correlation between cardiac output measurements determined by pulmonary or femoral arterial thermodilution in extreme situations of blood volume changes and vasopressor administration.
Section snippets
Materials and methods
The study was conducted with seven Maryland minipigs, isogenic for the major histocompatibility complex E-locus and weighing 9 ± 0.8 kg (range: 8–10 kg), and performed in accordance with the Guidelines for Ethical Conduct in the Care and Use of Animals and approved by the Institutional Review Board for the care of animal subjects. The animals were anaesthetised with atropine 0.02 mg/kg and ketamine 15 mg/kg, intubated and mechanically ventilated throughout the entire experiment. Mechanical
Response to acute hypovolaemia
After blood withdrawal, the animals presented a significant increase in heart rate (Figure 1) and a decrease in mean blood pressure (MBP) (Figure 2) and CVP (Table 1). There were significant decreases in CI (Figure 3), SVI, PAP, PCP, Dp/dtmax and CFI, as measured by both the PiCCO and Swan-Ganz (Table 1), with a significant increase in the SVRI (Figure 4). The blood volume variables (GEDVI and ITBI) (Figure 5, Figure 6) decreased considerably, whereas SVV increased (Table 1).
Response to rapid blood volume expansion
After volume
Discussion
Our model studied the immediate haemodynamic response to hypovolaemia, to rapid volume expansion with blood products and to vasopressor treatment in a model of previously healthy infant animals without hypoxia.
In clinical practice, the initial therapy for shock consists of volume expansion with crystalloids or colloids, which produce haemodilution. A number of experimental studies and several clinical trials with adults have compared the haemodynamic and survival effects of slow, moderate blood
Acknowledgements
We would especially like to thank Mercedes Adrados Plaza and Angélica Biurrun González of the Experimental Medicine Department of the Hospital Gregorio Marañón for their assistance in performing the experiments, as well as José María Bellón of the Preventive Medicine Department of the Hospital Gregorio Marañón for the statistical study. This study was funded by FIS (Fondo de Investigación Sanitaria) Grant No. 00/0013-06.
References (37)
- et al.
Assessment of cardiac output, intravascular volume status, and extravascular lung water by transpulmonary indicator dilution in critically ill neonates and infants
J Cardiothorac Vasc Anesth
(2002) - et al.
Early isotonic saline resuscitation from uncontrolled hemorrhage in rats
Surgery
(1998) - et al.
Pulmonary artery wedge pressure and extravascular lung water in patients with acute cardiogenic pulmonary edema requiring mechanical ventilation
Am J Cardiol
(1999) - et al.
Prediction of fluid responsiveness in patients during cardiac surgery
Br J Anaesth
(2004) - et al.
Optimizing fluid therapy in mechanically ventilated patients after cardiac surgery by on-line monitoring of left ventricular stroke volume variations. Comparison with aortic systolic pressure variations
Br J Anaesth
(2002) - et al.
Resuscitation of canine hemorrhagic hypotension with large-volume isotonic crystalloid: impact on lung water, venous admixture, and systemic arterial oxygen saturation
Am J Emerg Med
(1994) - et al.
Effect of crystalloid resuscitation and inhalation injury on extravascular lung water: clinical implications
Chest
(2002) - et al.
Haemodynamic and volumetric monitoring during haemorrhagic shock in swine
Resuscitation
(2001) - et al.
Neural mechanisms in the cardiovascular responses to acute central hypovolaemia
Clin Exp Pharmacol Physiol
(2001) - et al.
Pulmonary artery occlusion pressure and central venous pressure fail to predict ventricular filling volume, cardiac performance, or the response to volume infusion in normal subjects
Crit Care Med
(2004)
Monitoring of intrathoracic volemia and cardiac output in critically ill children
Minerva Anestesiol
Response to volume resuscitation in children with severe malaria
Pediatr Crit Care Med
American College of Critical Care Medicine Task Force Committee Members. Clinical practice parameters for hemodynamic support of pediatric and neonatal patients in septic shock
Crit Care Med
Assessment of cardiac preload and extravascular lung water by single transpulmonary thermodilution
Intensive Care Med
Immediate versus delayed fluid resuscitation for hypotensive patients with penetrating torso injuries
N Engl J Med
Hypotensive resuscitation during active hemorrhage: impact on in-hospital mortality
J Trauma
Timing and volume of fluid administration for patients with bleeding
Cochrane Database Syst Rev
Cited by (0)
- ☆
A Spanish translated version of the summary of this article appears as Appendix in the online version at 10.1016/j.resuscitation.2005.06.014.