Antidiuretic hormone (ADH) is a fundamental regulator of fluid and electrolyte homeostasis. Osmotically unregulated ADH secretion during intravenous fluid therapy has been implicated in the development of iatrogenic hyponatraemia. The case report and 3 prospective studies of this thesis provide evidence for this and examine the relative contributions of salinity versus infusion rate of intravenous fluids to the development of hyponatraemia. Two studies of plasma and urinary electrolytes and osmolality during intravenous rehydration of children with gastroenteritis were performed. The first, an observational study of 52 children receiving 0.45% (N/2) saline documented persistently raised plasma ADH concentrations independent of plasma sodium. In both studies, plasma and urinary biochemistry suggested osmotically unregulated ADH action. When N/2 and NS were compared in a randomised study of 102 children, NS emerged as superior in the prevention and correction of hyponatraemia, independent of infusion rate. In the third study, 124 pre-operative children were randomised to receive N/2 or NS intravenously at 100% or 50% of maintenance rates post-operatively. Plasma ADH concentrations increased in all groups, and the plasma and urinary biochemistry indicated persistent non-osmotic ADH activity in some children for up to 24 hours. Baseline urinary tonicity approximated NS. Comparison of urinary tonicity with the infused fluid largely explained changes observed in plasma sodium. The risk of hyponatraemia was decreased by isotonic saline but not fluid restriction; however plasma sodium concentration decreased in the NS 100% group between 8 and 24 hours, suggesting that a decreased rate should be considered during prolonged intravenous fluid administration. Fourteen (23%; 7NS) of those on 50% maintenance were assessed as dehydrated, with hypernatraemia in 3 receiving NS50%. The chloride load associated with NS in the second and third studies was not associated with the development of acidosis. The studies also showed that 2.5% dextrose resolved and prevented hypoglycaemia in children with gastroenteritis but was inadequate to prevent hypoglycaemia and/or ketosis in 38% of children under 6 years when infused at maintenance rates. Non-osmotically regulated ADH activity in hospitalised children is common, in the face of which, isotonic is superior to hypotonic saline in decreasing the risk of hyponatraemia.

L’optimisation hémodynamique péri-opératoire est une stratégie qui vise à maximaliser le transport artériel en oxygène et/ou le volume d’éjection systolique lors de chirurgie à risque. Ce concept a beaucoup évolué lors de ces trente dernières années, vers une approche plus simple, plus réalisable en pratique clinique et moins invasive. Les principales thérapeutiques utilisées dans les différents protocoles d’optimisation hémodynamique sont le remplissage vasculaire, l’administration d’agents inotropes et de vasopresseurs. Cependant, les conséquences physiopathologiques de l’agression chirurgicale peuvent impacter grandement les modalités d’administration et l’efficacité des thérapeutiques précitées. Dans la première étude, nous avons décrit l’impact de l’acidose respiratoire et métabolique (fréquemment rencontrées lors de chirurgie majeure et/ou de coeliochirurgie) sur l’efficacité des agents α et β-adrénergiques sur le myocarde sain de rat. Dans un deuxième travail nous avons mis en évidence que le remplissage vasculaire ne pouvait pas être guidé par des indices dynamiques de précharge dépendance lors du clampage chirurgicale de l’aorte abdominale sous-rénale, dans un modèle porcin. Enfin, dans la troisième étude, nous avons montré dans un modèle clinique, que le positionnement en décubitus ventral lors d’une chirurgie du rachis entrainait des modifications majeures des interactions cardiorespiratoires et que les indices dynamiques devaient être interprétés avec prudence pour guider le remplissage vasculaire dans ce contexte. Ces études translationnelles soulignent trois situations fréquentes impactant l’efficacité et/ou les modalités d’administration des thérapeutiques nécessaires à une optimisation hémodynamique peropératoire / The aim of perioperative haemodynamic optimization is to maximize oxygen delivery and/or stroke volume during high risk surgery. This concept has evolved during the last thirty years, to a simpler, more feasible and less invasive approach. Main treatments used in different hemodynamic optimization protocols are fluid loading, inotropes and vasopressors administration. However, pathophysiological consequences of surgical stress can greatly impact the mode of administration and the efficacy of the above therapeutics. In the first study, we described the impact of respiratory and metabolic acidosis (frequently encountered during major surgery and/or laparoscopic surgery) on the effectiveness of α and β-adrenergic agents in healthy rat myocardium. In a second work, we demonstrated that intravenous fluids cannot be guided by dynamic indices of preload dependency during surgical clamping of the infrarenal abdominal aorta in a porcine model. Finally, in the third study, we demonstrated in a clinical model, that positioning in prone position during spine surgery induced major changes in cardiorespiratory interactions and dynamic indices should be interpreted with caution to guide fluid therapy in this context. These translational studies highlight three common situations impacting the effectiveness and/or administration of therapeutic necessary for intraoperative hemodynamic optimization.

MCur / Department of Advanced Nursing Science / See the attached abstract below