Arterial hyperoxia and mortality in critically ill patients: a systematic review and meta-analysis

Introduction

The safety of arterial hyperoxia is under increasing scrutiny. We performed a systematic review of the literature to determine whether any association exists between arterial hyperoxia and mortality in critically ill patient subsets.

Methods

Medline, Thomson Reuters Web of Science and Scopus databases were searched from inception to June 2014. Observational or interventional studies evaluating the relationship between hyperoxia (defined as a supranormal arterial O₂ tension) and mortality in adult intensive care unit (ICU) patients were included. Studies primarily involving patients with exacerbations of chronic pulmonary disease, acute lung injury and perioperative administration were excluded. Adjusted odds ratio (OR) of patients exposed versus those not exposed to hyperoxia were extracted, if available. Alternatively, unadjusted outcome data were recorded. Data on patients, study characteristics and the criteria used for defining hyperoxia exposure were also extracted. Random-effects models were used for quantitative synthesis of the data, with a primary outcome of hospital mortality.

Results

In total 17 studies (16 observational, 1 prospective before-after) were identified in different patient categories: mechanically ventilated ICU (number of studies (k) = 4, number of participants (n) = 189,143), post-cardiac arrest (k = 6, n = 19,144), stroke (k = 2, n = 5,537), and traumatic brain injury (k = 5, n = 7,488). Different criteria were used to define hyperoxia in terms of PaO₂ value (first, highest, worst, mean), time of assessment and predetermined cutoffs. Data from studies on ICU patients were not pooled because of extreme heterogeneity (inconsistency (I²) 96.73%). Hyperoxia was associated with increased mortality in post-cardiac arrest patients (OR = 1.42 (1.04 to 1.92) I² 67.73%) stroke (OR = 1.23 (1.06 to 1.43) I² 0%) and traumatic brain injury (OR = 1.41 (1.03 to 1.94) I² 64.54%). However, these results are limited by significant heterogeneity between studies.

Conclusions

Hyperoxia may be associated with increased mortality in patients with stroke, traumatic brain injury and those resuscitated from cardiac arrest. However, these results are limited by the high heterogeneity of the included studies.

Electronic supplementary material

The online version of this article (doi:10.1186/s13054-014-0711-x) contains supplementary material, which is available to authorized users.     

Inflammation biomarkers and delirium in critically ill patients

Introduction

Delirium is a common occurrence in critically ill patients and is associated with an increase in morbidity and mortality. Septic patients with delirium may differ from a general critically ill population. The aim of this investigation was to study the relationship between systemic inflammation and the development of delirium in septic and non-septic critically ill patients.

Methods

We performed a prospective cohort study in a 20-bed mixed intensive care unit (ICU) including 78 (delirium = 31; non-delirium = 47) consecutive patients admitted for more than 24 hours. At enrollment, patients were allocated to septic or non-septic groups according to internationally agreed criteria. Delirium was diagnosed using the Confusion Assessment Method for the Intensive Care Unit (CAM-ICU) during the first 72 hours of ICU admission. Blood samples were collected within 12 hours of enrollment for determination of tumor necrosis factor (TNF)-α, soluble TNF Receptor (STNFR)-1 and -2, interleukin (IL)-1β, IL-6, IL-10 and adiponectin.

Results

Out of all analyzed biomarkers, only STNFR1 (P = 0.003), STNFR2 (P = 0.005), adiponectin (P = 0.005) and IL-1β (P < 0.001) levels were higher in delirium patients. Adjusting for sepsis and sedation, these biomarkers were also independently associated with delirium occurrence. However, none of them were significant influenced by sepsis.

Conclusions

STNFR1, STNFR2, adiponectin and IL-1β were associated with delirium. Sepsis did not modify the relationship between the biomarkers and delirium occurrence.     

Acute kidney injury survivors should have long-term follow-up

Acute kidney injury (AKI) is a frequently occurring complication in ICU patients and is associated with decreased short- and long-term survival. Gammelager and colleagues showed that AKI patients are at increased risk for developing heart failure and myocardial infarction at long-term follow-up. Their study provides strong epidemiological data on cardiorenal syndrome type 3, and their findings help explain the worse long-term survival of AKI patients. Finally, it also highlights the need for specific follow-up programs for ICU survivors.In a recent article, Gammelager and colleagues [1] investigated the association between acute kidney injury (AKI) and long-term cardiac morbidity and stroke in a representative ICU cohort. AKI occurs in one- to two-thirds of ICU patients and is associated with worse outcome [2,3]. Short-term worse outcomes can be explained by the effects of decreased kidney function, such as volume overload and retention of uremic toxins [4]. Long-term outcomes are probably affected by development of chronic kidney disease [5]. Recently, there has been increased interest in the complex interaction between the kidney and heart. AKI leading to acute cardiac events has been termed cardiorenal syndrome type 3 (CRS-3) [6]. At present this concept is only sparsely supported by human data [7]. The study by Gammelager and colleagues is one of the first providing high-quality data on CRS-3 in ICU patients.Several groups, including the group of Gammelager and colleagues, have demonstrated worse long-term outcomes for AKI patients [3,8-11]. The present study by Gammelager and colleagues demonstrates that cardiovascular disease may contribute to these worse outcomes. Over a 3-year period, AKI stage 1 and greater was associated with heart failure (hazard ratio 1.33), and AKI stages 2 and 3 were associated with myocardial infarction (hazard ratio 1.51). Similar findings were reported before by James and colleagues [12] in a cohort of non-ICU patients after coronary angiography. The paper by Gammelager and colleagues is one of the first providing long-term epidemiologic data on CRS-3 in ICU patients. Importantly, it shows that CRS-3 is also relevant for patients discharged from the ICU, a less well-recognized aspect of CRS-3.These findings are strengthened by the methodological quality of the study. Selection bias was limited by including a large multicenter ICU cohort, and a population-based medical registry guaranteed virtually complete patient follow-up. Studies using different AKI definitions cannot be compared. Therefore, it is crucial that the universally accepted KDIGO (Kidney Disease: Improving Global Outcomes) definition for AKI was used [13].A limitation is that administrative data were used for recoding of the endpoints. Administrative databases may be limited by both over- and under-reporting, and also miss detailed information on, for example, severity of heart failure. Also, an epidemiologic study can only demonstrate an association, rather than prove a causal effect, in this case between AKI and cardiac events. These data on CRS-3 are therefore hypothesis generating and should prompt further research on the pathophysiologic mechanisms explaining the worse cardiovascular outcomes.How can we explain this increased risk for cardiovascular events? This may be mediated, especially in the long-term, by chronic kidney disease developing after AKI, but other factors may also play a role [5]. In the acute phase, AKI may exert a negative impact on the heart, leading to cellular response with apoptosis, remodeling and fibrosis, which may ultimately lead to arrhythmias, conduction abnormalities, heart failure, and ischemia [7,14].The study by Gammelager and colleagues is also one of the few that reports on the association between AKI and stroke, but showed no association during the 3-year follow-up. These findings are in contrast to those found in Taiwan by Wu and colleagues [15], where in a matched case-controlled study AKI patients had a higher risk and higher severity of stroke than non-AKI patients. An important difference with the cohort of Gammelager and colleagues was that the study cohort included only severe AKI treated with renal replacement therapy and was not limited to ICU patients. Severity of AKI may therefore play a role in risk for stroke.Another important lesson that can be learned from these long-term outcome data is that AKI survivors should have long-term follow-up. We were already aware that follow-up of kidney function is important, but these data also highlight the importance of cardiovascular follow-up. As other types of ICU survivors also have specific long-term morbidity issues, this highlights the need for specific and multidisciplinary follow-up programs for ICU survivors.     

Effect of plant sterols in combination with other cholesterol-lowering foods

The National Cholesterol Education Program Adult Treatment Panel III guidelines advocate effective combinations of cholesterol-lowering dietary components. This approach (dietary portfolio) produces large reductions in serum cholesterol, but the contribution of individual components remains to be established. We therefore assessed the effect of eliminating one out of the 4 dietary portfolio components. Plant sterols were selected because at 2 g/d, they have been reported to reduce low-density lipoprotein cholesterol (LDL-C) by 9% to 14%. Forty-two hyperlipidemic subjects were prescribed diets high in soy protein (22.5 g/1000 kcal), viscous fibers (10 g/1000 kcal), and almonds (23 g/1000 kcal) for 80 weeks. Subjects were instructed to take these together with plant sterols (1.0 g/1000 kcal) except between weeks 52 and 62. While taking the full dietary portfolio, including plant sterols, mean LDL-C reduction from baseline was 15.4% +/- 1.6% (P < .001). After sterol elimination, mean LDL-C reduction was 9.0% +/- 1.5% (P < .001). Comparable LDL-C reductions were also seen for the 18 subjects with a complete data set: on plant sterols, 16.7% +/- 3.1% (P < .001) and off plant sterols, 10.3% +/- 2.6% (P < .001), resulting in a 6.3% +/- 2.0% (P = .005) difference attributable to plant sterols. Compliance in this group of 18 was 67.0% +/- 5.9% for plant sterols and 61.9% +/- 4.8% for the other components. In combination with other cholesterol-lowering foods and against the background of a low-saturated fat diet, plant sterols contributed over one third of the LDL-C reduction seen with the dietary portfolio after 1 year of following dietary advice.     

Successful treatment of Fusarium keratitis with cornea transplantation and topical and systemic voriconazole

A case of invasive Fusarium keratitis in a previously healthy male patient was treated successfully with cornea transplantation and systemic and topical voriconazole after treatment failure with topical amphotericin B and systemic itraconazole. Topical voriconazole was well tolerated, and, in conjunction with the oral administration, it resulted in a high level of the drug in the anterior chamber of the eye (which was 160% of the plasma drug level).