Supplemental Oxygen in Hypovolemia
Condition: Hypovolemia; Hyperoxia
MeSH terms: Hyperoxia; Hypovolemia
Study type: Interventional
Phase: Phase 1

Summary: 
      Supplemental oxygen is frequently administered in acutely and critically ill patients,
      specifically, it is often administered in trauma patients to avoid arterial hypoxemia and
      tissue hypoxia. There is also an increasing focus on potentially deleterious effects of
      hyperoxia. Further, the hemodynamic response to hyperoxia in hypovolemia is poorly
      understood.

      The present study aims to investigate the effects of supplemental oxygen on systemic and
      cerebral hemodynamics in simulated hypovolemia in healthy volunteers.
    

Detailed description: 
      The overriding goal for the resuscitation of any critically ill patient is to ensure adequate
      oxygen delivery. In critically ill patients, SaO2 and PaO2 may be reduced due to lung
      dysfunction (e.g. atelectasis and shunt flow). Under normal circumstances, SaO2 is near to
      100%, and supplemental oxygen can not increase this further. Thus, in this circumstance,
      providing supplemental oxygen will only increase a small, dissolved proportion. Although this
      proportion may be a significant fraction in some circumstances, the intention of giving
      supplemental oxygen is in most circumstances to ensure a high SaO2. Supplemental oxygen has
      been extensively used in acutely critically ill patients to avoid hypoxemia, and is
      recommended in severely injured trauma patients, as given by the statement: "Supplemental
      oxygen must be administered to all severely injured trauma patients." in the ATLS (Advanced
      Trauma Life Support) guidelines.

      Accordingly, supplemental oxygen is often given to trauma patients, often resulting in
      hyperoxia. The clinical evidence for providing supplemental oxygen in all trauma patients is
      however scarce. The liberal use of supplemental oxygen has also largely been founded on a
      perception that supplemental oxygen is harmless, and that it is safer to err on the side of
      hyperoxia. There is however an increasing focus on possible deleterious effects of hyperoxia,
      especially in specific clinical circumstances. This has led to recommendations of more
      restrictive use of supplemental oxygen, often titrated to no more than what is necessary to
      achieve an adequate arterial oxygen saturation (e.g. in the range 94-98%).

      In the initial treatment of trauma patients, detection and treatment of hypovolemia is of
      paramount importance. Hypovolemia leads to reduced cardiac filling and stroke volume. Under
      normal circumstances in unanesthetized humans, this is compensated by an increase in systemic
      vascular resistance and heart rate to maintain a normal or near-normal mean arterial pressure
      (MAP). At some point, these compensatory mechanisms are exhausted, and MAP typically falls
      abruptly.

      Lower body negative pressure (LBNP) is a model of central hypovolemia where negative pressure
      is applied to the body from the waist-down. Thereby, blood is displaced from the central
      compartment of the upper body to the lower extremities and pelvis. The model has been used
      for more than half a century and is considered useful model for studying hypovolemia in
      conscious volunteers.

      Normobaric hyperoxia induces vasoconstriction and reduced blood flow to several organs,
      including the brain, heart and skeletal muscle. One could therefore hypothesize hyperoxia
      leading to both an increased tolerance to hypovolemia mediated by vasoconstriction as well as
      a reduced tolerance mediated by reduced cerebral blood flow. One study using the LBNP-model
      did not find that supplemental oxygen significantly affected the hemodynamic response to
      simulated hypovolemia. This study did however only apply one level of LBNP and did not
      specifically study cerebral circulation.

      Based on the above, there is a need for studies on the effects of normobaric hyperoxia on the
      hemodynamic response to hypovolemia. In the present study, we will study the effect of
      supplemental oxygen in the LBNP-model of hypovolemia in a crossover study on healthy
      volunteers.

      In the present study, 15 healthy volunteers will be exposed to LBNP with oxygen or room air
      in randomized order in a crossover fashion. We will measure cardiac outout, stroke volume and
      middle cerebral artery blood velocity to explore effects of oxygen on these variables during
      hypovolemia.
    

Intervention name(s): Oxygen gas; Air
Intervention type(s): Drug; Drug
Intervention description(s): Oxygen 15 l/min; Room air 15 l/min
Allocation: Randomized
Intervention model: Crossover Assignment
Intervention model description: Double-blind, randomized, crossover design.
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary purpose: Basic Science