Variability in targeted arterial oxygenation levels in patients with severe sepsis or septic shock

ORIGINAL ARTICLE Variability in targeted arterial oxygenation levels in patients with severe sepsis or septic shock R. M. Dahl1, L. Grønlykke2, N. Ha...
Author: Elijah Daniel
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ORIGINAL ARTICLE

Variability in targeted arterial oxygenation levels in patients with severe sepsis or septic shock R. M. Dahl1, L. Grønlykke2, N. Haase3, L. B. Holst3, A. Perner3, J. Wetterslev4, B. S. Rasmussen5, C. S. Meyhoff1 and the 6S-Trial and TRISS Trial investigators 1

Department of Anaesthesiology, Herlev Hospital, University of Copenhagen, Herlev, Denmark Department of Anaesthesiology, Nordsjællands Hospital – Hillerød, University of Copenhagen, Hillerød, Denmark 3 Department of Intensive Care 4131, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark 4 Copenhagen Trial Unit, Centre for Clinical Intervention Research, Copenhagen, Denmark 5 Department of Anaesthesiology, Aalborg Hospital, University of Aalborg, Aalborg, Denmark 2

Correspondence R. M. Dahl, Department of Anaesthesiology, Herlev Hospital, University of Copenhagen, Herlev Ringvej 75, Pavillon 10, I65F10, DK-2730 Herlev, Denmark E-mail: [email protected] Conflicts of interest The authors have no conflicts of interest. Funding No funding was received for this study, but the original 6S and TRISS trials were funded as described in the respective publications (Ref. 14 and 17). Submitted 2 February 2015; accepted 5 March 2015; submission 27 October 2014. Citation Dahl RM, Grønlykke L, Haase N, Holst LB, Perner A, Wetterslev J, Rasmussen BS, Meyhoff CS. Variability in targeted arterial oxygenation levels in patients with severe sepsis or septic shock. Acta Anaesthesiologica Scandinavica 2015. doi: 10.1111/aas.12528

Background: Supplemental oxygen therapy is used for intensive care (ICU) patients with severe sepsis, but with no general guidelines and few safety data. The aim of this observational study was to describe the variability in oxygen administration as well as the association between partial pressure of arterial oxygen (PaO2) and mortality. Methods: We extracted data from two Scandinavian clinical trials of ICU patients with severe sepsis or septic shock. We calculated average PaO2 and fraction of inspired oxygen (FiO2) from trial inclusion and the following 5 days, and assessed the association between PaO2 and 90-day mortality. Results: The median PaO2 was 9.8 kPa [5–95% range 6.4–19.9] and FiO2 was 0.51 [5–95% range 0.27–1.00], respectively. Eight hundred and five of 1,770 patients (45%) died. The relative risk of mortality was 1.43 [95% CI: 1.19–1.65] in patients with average PaO2 < 8 kPa and 1.29 [95% CI: 0.84–1.68] in patients with average PaO2 ≥ 16 kPa, as compared to patients with average PaO2 10–12 kPa. The relative risk of mortality was 1.38 [95% CI: 1.17– 1.58] in patients with an average FiO2 0.60–0.80 and 2.10 [95% CI: 1.88–2.23] in patients with an average FiO2 ≥ 0.80 as compared to patients with an average FiO2 ≤ 0.40. Conclusion: Administration of oxygen in patients with severe sepsis resulted in a wide range of PaO2. Significantly higher mortality was observed in patients with an average PaO2 < 8 kPa and FiO2 ≥ 0.60. The results do not imply causation and the associations between average PaO2 and adverse outcomes have to be assessed further.

Editorial comment: what this article tells us

Large multicenter studies within intensive care medicine create large high quality databases. Here, Dahl et al. take advantage of the successful studies in SCCTG to highlight the association between oxygenation and outcomes. Observational studies can only be hypothesis generating, but highquality observations may generate high-quality hypotheses.

Acta Anaesthesiologica Scandinavica 59 (2015) 859–869 ª 2015 The Acta Anaesthesiologica Scandinavica Foundation. Published by John Wiley & Sons Ltd

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Oxygen is one of the most common drugs used in medical care, the main indications being present hypoxemia or risk of hypoxemia. Severe sepsis involves tissue hypoxemia, and therefore, administration of oxygen plays an important role as an assumed lifesaving intervention.1,2 However, few data are available regarding the safety of oxygen administration in patients admitted to the intensive care unit (ICU) with severe sepsis or septic shock. The Surviving Sepsis Campaign contains only recommendations for patients having ARDS, in which a wide range of arterial oxygen saturation, between 88% and 95%, is aimed.3 Recent findings in anesthesia and emergency medicine may indicate harmful effects when administering oxygen at high concentrations in the treatment of patients with acute exacerbations of chronic obstructive pulmonary disease (COPD),4 traumatic brain injury,5 during resuscitation after cardiac arrest,6,7 and during abdominal laparotomy.8 Moreover, a number of basic physiological results indicate both advantages and disadvantages of high-dose oxygen for sepsis, including deteriorated respiratory function.9 Current use of oxygen in patients with severe sepsis is highly variable,10 ranging from a clinical practice where low partial pressure of arterial oxygenation (PaO2) values (6–8 kPa) are accepted to deliberately increase PaO2 to supranormal values (≥ 15 kPa) in an attempt to apply a high gradient of oxygen to suffering organs.11–13 The aim of this study was to describe the current practice of oxygen administration in patients with severe sepsis or septic shock using descriptive data from two large randomized clinical trials in Scandinavia,14,15 and secondly, to describe the association between PaO2 and 90day mortality.

Methods We extracted data regarding oxygen treatment and outcomes from two multicenter trials of patients with severe sepsis or septic shock, the 6S-trial (NCT00962156)14,16 and TRISS trial (NCT01485315).15,17 The 6S-trial included 804 patients with severe sepsis or septic shock in 26

Scandinavian ICUs between December 23, 2009, and November 15, 2011. Patients were randomly assigned to fluid resuscitation with either 6% HES (hydroxyethyl starch) 130/0.42 (Tetraspan) or Ringer’s acetate. Patients were eligible if they were 18 years of age or older and fulfilled the criteria for severe sepsis within the previous 24 h. The primary outcome was composite death or dependence of renal replacement therapy (RRT) 90 days after randomization.14 The TRISS trial included 1005 patients with septic shock in 32 Scandinavian ICUs between December 3, 2011, and December 26, 2013. Patients were randomized to receive transfusion with pre-storage leukocyte-reduced red bloods cells (RBC) suspended in saline–adenine–glucose and mannitol (SAGM) at hemoglobin (Hb) levels of 4.3 mM (7 g/dl) or below vs. 5.6 mM (9 g/dl) or below; the primary outcome was 90day mortality. Patients were eligible if they were 18 years of age or older, had anemia (Hb ≤ 9 g/dl), and fulfilled the criteria for septic shock.15 In this observational analysis, we applied availability of 90-day mortality data as an exclusion criterion, which left us with data from 797 patients from the 6S-trial, and 973 patients from the TRISS trial resulting in complete outcome status on 97.2% of the included patients.

Data extraction Baseline data were extracted including the SAPS II and SOFA scores, source of sepsis, and whether the patient received mechanical ventilation, had shock, or had acute kidney injury at randomization. The PaO2 and FiO2 from the lowest PaO2/FiO2 ratio (PF-ratio) were measured at baseline, defined as the closest value to randomization within 24 h before randomization, and one time daily the first 5 days after randomization. If patients were spontaneously breathing, the FiO2 was estimated from the delivered flows of oxygen and air.18 We used interpolation if data were missing between two known measurements, but extrapolation was not used. The average PaO2 from these six measurements was calculated, and patients were categorized into the following groups: Acta Anaesthesiologica Scandinavica 59 (2015) 859–869

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ª 2015 The Acta Anaesthesiologica Scandinavica Foundation. Published by John Wiley & Sons Ltd

OXYGENATION LEVELS IN SEVERE SEPSIS

1. 2. 3. 4. 5.

average PaO2 < 8 kPa; 8 kPa ≤ average PaO2 < 10 kPa; 10 kPa ≤ average PaO2 < 12 kPa; 12 kPa ≤ average PaO2 < 16 kPa; average PaO2 ≥ 16 kPa.

≥ 40 kPa), and average PF-ratio from day 1 to 5 (

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