Hyperoxia and hypertonic saline in patients with septic shock (HYPERS2S): a two-by-two factorial, multicentre, randomised, clinical trial

Asfar, Pierre; Schortgen, Frédérique; Boisramé-Helms, Julie; Charpentier, Julien; Guérot, Emmanuel; Mégarbane, Bruno; Grimaldi, David; Grelon, Fabien; Anguel, Nadia; Lasocki, Sigismond; Henry-Lagarrigue, Matthieu; Gonzalez, Frédéric; Legay, François; Guitton, Christophe; Schenck, Maleka; Doise, Jean Marc; Devaquet, Jérôme; Linden, Thierry Van Der; Chatellier, Delphine; Rigaud, J.; Dellamonica, Jean; Tamion, Fabienne; Meziani, Ferhat; Mercat, Alain; Dreyfuss, Didier; Seegers, Valérie; Radermacher, Peter

doi:10.1016/s2213-2600(17)30046-2

Cited by 230 publications

(251 citation statements)

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“…In fact, in critically ill patient groups where lung function was relatively preserved, such as patients post cardiac arrest, harm was mainly associated with systemic oxygen tensions over 300 mmHg [13]. Greater degrees of hyperoxemia were likely in both the study by Girardis et al [24] and in the HYPERS2S trial [23] of "induced" systemic hyperoxemia in patients with sepsis. Our study was focused solely on patients with ARDS, where due to their impaired gas exchange, they cannot attain this severity of systemic hyperoxia.…”

Section: Hyperoxemia In Ardsmentioning

confidence: 99%

“…Potential mechanisms of oxygen toxicity remain poorly understood and may include systemic arterial vasoconstriction [18,19], and cytotoxic effects of reactive oxygen species [20][21][22]. In randomized trials, "induced" hyperoxia (using 100% oxygen) increased 28-day mortality in septic shock patients [23], while critically ill patients randomized to a target arterial oxygen tension (PaO 2 ) of 70-100 mmHg had lower mortality compared to patients with a "conventional" target of PaO 2 up to 150 mmHg [24] in a single-center study. While a recent large international multicenter trial demonstrated no effect of conservative oxygen therapy in a diverse cohort of critically ill patients [25], a subsequent sub-study raised the possibility of clinically important harm with conservative oxygen therapy in patients with sepsis [26].…”

Section: Introductionmentioning

confidence: 99%

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Hyperoxemia and excess oxygen use in early acute respiratory distress syndrome: insights from the LUNG SAFE study

et al. 2020

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Background: Concerns exist regarding the prevalence and impact of unnecessary oxygen use in patients with acute respiratory distress syndrome (ARDS). We examined this issue in patients with ARDS enrolled in the Large observational study to UNderstand the Global impact of Severe Acute respiratory FailurE (LUNG SAFE) study. Methods:In this secondary analysis of the LUNG SAFE study, we wished to determine the prevalence and the outcomes associated with hyperoxemia on day 1, sustained hyperoxemia, and excessive oxygen use in patients with early ARDS. Patients who fulfilled criteria of ARDS on day 1 and day 2 of acute hypoxemic respiratory failure were categorized based on the presence of hyperoxemia (PaO 2 > 100 mmHg) on day 1, sustained (i.e., present on day 1 and day 2) hyperoxemia, or excessive oxygen use (FIO 2 ≥ 0.60 during hyperoxemia). Results: Of 2005 patients that met the inclusion criteria, 131 (6.5%) were hypoxemic (PaO 2 < 55 mmHg), 607 (30%) had hyperoxemia on day 1, and 250 (12%) had sustained hyperoxemia. Excess FIO 2 use occurred in 400 (66%) out of 607 patients with hyperoxemia. Excess FIO 2 use decreased from day 1 to day 2 of ARDS, with most hyperoxemic patients on day 2 receiving relatively low FIO 2 . Multivariate analyses found no independent relationship between day 1 hyperoxemia, sustained hyperoxemia, or excess FIO 2 use and adverse clinical outcomes. Mortality was 42% in patients with excess FIO 2 use, compared to 39% in a propensity-matched sample of normoxemic (PaO 2 55-100 mmHg) patients (P = 0.47).Conclusions: Hyperoxemia and excess oxygen use are both prevalent in early ARDS but are most often non-sustained. No relationship was found between hyperoxemia or excessive oxygen use and patient outcome in this cohort. Trial registration: LUNG-SAFE is registered with ClinicalTrials.gov, NCT02010073

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Section: Hyperoxemia In Ardsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Hyperoxemia and excess oxygen use in early acute respiratory distress syndrome: insights from the LUNG SAFE study

et al. 2020

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“…Hyperoxia has been shown to be associated with increased mortality in patients with cardiac arrest, 11,12 stroke, 13 acute myocardial infarction, 14 and septic shock. 15 Breathing 30 -60 min of supplementary oxygen at 28% has been shown to lead to elevated systemic and airway markers of oxidative stress and inflammatory cytokines in both healthy volunteers and patients with COPD. 16,17 In addition, hyperoxia has been shown to be associated with acute lung injury and bacterial dissemina-tion in animal models.…”

Section: Discussionmentioning

confidence: 99%

Post-Hospitalization Short-Term Oxygen Therapy: Use of a Clinical Management Pathway and Long-Term Follow-Up

2018

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BACKGROUND: Home oxygen therapy is commonly prescribed for patients who remain hypoxemic at hospital discharge, although evidence supporting this practice is lacking. This study aimed to evaluate oxygen prescription and follow-up for patients who were prescribed post-discharge short-term oxygen therapy (STOT) and to assess their long-term outcome. METHODS: A retrospective audit was undertaken of subjects prescribed STOT following hospitalization at a single site in Melbourne, Australia, between January 2011 and December 2015. During the study period, a designated clinical pathway for STOT prescription and follow-up after hospital discharge was in place. Chart review was performed to collect subject demographics and comorbidities, results of oxygen assessment (arterial blood gas and 6-min walk tests) and prescription, and results at follow-up re-assessment and mortality. RESULTS: Over five 5 years, 205 subjects were prescribed STOT upon hospital discharge. Common indications for oxygen treatment were chronic lung disease (54%) and dyspnea palliation (26%). Of the 152 subjects who were discharged with non-palliative oxygen therapy, 28% did not fulfil the recommended prescribing criteria or did not have recommended assessments. Among the 118 subjects who returned for re-assessment 4 weeks after initial oxygen provision, 47 (40%) did not fulfill criteria for long-term oxygen therapy. The 1-y cumulative survival rate for the study population was 56%. CONCLUSIONS: A significant proportion of subjects who were prescribed post-discharge STOT did not fulfill the recommended prescribing criteria. The long-term prognosis for subjects who were prescribed postdischarge STOT was poor.

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“…It was argued in the SPLIT trial that the severity of patients mirrored by the mortality rate (7.6 and 8.6% in the PlasmaLyte ® and saline groups, respectively) and low fluid requirements was low (2.7 vs 2.6 l, respectively) and may have explained the absence of beneficial effects of PlasmaLyte ® . However, two other recent large controlled randomized studies, with higher chloride amounts, in patients presenting high risk of renal acute injury, comparing 3% NaCl to 0.9% NaCl in patients in septic shock for the first one and comparing 0.9% NaCl to PL in patients after cardiac surgery for the second one, reported both hyperchloremic acidosis in patients receiving higher load of chloride but did not reported any detrimental renal effect for these patients [24, 25]. …”

Section: Discussionmentioning

confidence: 99%

Assessment of renal hemodynamic toxicity of fluid challenge with 0.9% NaCl compared to balanced crystalloid (PlasmaLyte®) in a rat model with severe sepsis

Olivier

Beloncle

Seegers

et al. 2017

Ann. Intensive Care

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BackgroundAccording to international guidelines, volume expansion with crystalloids is the first-line treatment for hemodynamic management in patients with severe sepsis or septic shock. Compared to balanced crystalloids, 0.9% sodium chloride (0.9% NaCl) induces hyperchloremia and metabolic acidosis and may alter renal hemodynamics and function. We compared the effects of 0.9% NaCl to a less chloride-concentrated fluid, PlasmaLyte® (PL) in targeted fluid resuscitation in a randomized, double-blind controlled study in an experimental model of severe sepsis in rats.ResultsA sepsis with hypotension was induced by cecal ligature and puncture (CLP) in 40 male Wistar rats (20 for each crystalloid). Rats received fluid resuscitation over a period of 200 min for a targeted mean arterial pressure of 90 mm Hg. Animals received similar volumes of 0.9% NaCl or PL. Unlike PL-resuscitated rats, 0.9% NaCl-resuscitated rats experienced hyperchloremia and metabolic acidosis, whereas systemic hemodynamics, renal hemodynamics and renal function were not significantly different between both groups.ConclusionIn our model of rats with severe sepsis resuscitated with large amounts of crystalloids, 0.9% NaCl-induced hyperchloremic acidosis, but balanced crystalloid did not improve systemic and renal hemodynamics or renal function.Electronic supplementary materialThe online version of this article (doi:10.1186/s13613-017-0286-1) contains supplementary material, which is available to authorized users.

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Hyperoxia and hypertonic saline in patients with septic shock (HYPERS2S): a two-by-two factorial, multicentre, randomised, clinical trial

Cited by 230 publications

References 34 publications

Hyperoxemia and excess oxygen use in early acute respiratory distress syndrome: insights from the LUNG SAFE study

Hyperoxemia and excess oxygen use in early acute respiratory distress syndrome: insights from the LUNG SAFE study

Post-Hospitalization Short-Term Oxygen Therapy: Use of a Clinical Management Pathway and Long-Term Follow-Up

Assessment of renal hemodynamic toxicity of fluid challenge with 0.9% NaCl compared to balanced crystalloid (PlasmaLyte®) in a rat model with severe sepsis

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