Research in context
Evidence before this study
We searched PubMed for all manuscripts published in English, German, and French before July 31, 2016, using the search terms “septic shock” OR “ARDS” OR “hyperoxia” OR “hypertonic saline” OR “small volume resuscitation”. We reviewed all articles that reported results of therapeutic interventions, including observational studies and controlled trials.
At the time of the design of our study (2012), hyperoxia had been shown to have vasoconstrictor properties, thus potentially allowing for haemodynamic stabilisation in vasodilatory shock. Additionally, several studies had shown that perioperative hyperoxia could reduce surgical site infection, particularly after colorectal surgery. The most recent meta-analyses on the association of hyperoxia and outcome in critically ill patients in general published in 2014 and 2015 concluded that the existing results are inconclusive because of substantial heterogeneity, and that additional evidence is needed.
Hypertonic saline had been shown to be an alternative approach for fluid resuscitation in shock states because of its volume sparing effect, but we found only five small-sized, short-term studies in patients with septic shock showing improved haemodynamic stability and attenuated markers of inflammation. Moreover, most of these trials used hypertonic fluid preparations in combination with synthetic colloid solutions; however, synthetic colloid solutions are no longer recommended in patients with septic shock.
So far, no pulmonary oxygen toxicity had been shown for hyperoxia during mechanical ventilation for up to 24 h. In view of the potentially favourable haemodynamic and antimicrobial effects of hyperoxia and the beneficial haemodynamic effects of hypertonic saline, we designed the Hyperoxia and Hypertonic Saline in Septic Shock (HYPER2S) trial assessing the effects of ventilation with 100% oxygen (FiO2=1·0) and 3% hypertonic saline for fluid resuscitation in patients with septic shock.
Added value of this study
Our study is the first large randomised controlled trial assessing both the potential benefit and the risks of hyperoxia and hypertonic saline in septic shock. Despite a significantly lower sequential organ failure score during the first 7 days of observation, mechanical ventilation with 100% oxygen during the first 24 h of septic shock increased the risk of death. Hypertonic saline had only a limited volume sparing effect, and did not improve any outcome variable.
Implications of all the available evidence
The findings of HYPER2S concerning ventilation with 100% oxygen are consistent with the most recent meta-analyses, showing that very high arterial oxygen partial pressures are associated with an increased risk of mortality. The findings of HYPER2S concerning hypertonic saline are consistent with previous trials in patients with trauma resuscitation, showing that hypertonic fluid resuscitation does not improve outcome. Taken together, these findings do not support the use of hyperoxia or hypertonic saline during the early management of patients with septic shock.