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 Table of Contents  
ORIGINAL ARTICLE
Year : 2020  |  Volume : 7  |  Issue : 1  |  Page : 15-19

Comparative study of excessive oxygen therapy effects on critically ill patients’ outcome


Department of Critical Medicine, Faculty of Medicine, University of Alexandria, Alexandria, Egypt

Date of Submission03-Dec-2018
Date of Acceptance12-Dec-2018
Date of Web Publication16-Apr-2020

Correspondence Address:
MD Waleed S Abdelhady Mohamed
Department of Critical Medicine, Faculty of Medicine, University of Alexandria, Alexandria
Egypt
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/roaic.roaic_97_18

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  Abstract 

Introduction The use of oxygen in medicine became common around 1917 and is believed to be the most common treatment given in hospitals in the developed world.
Aim of the work This study was aimed to compare and evaluate the effects of excessive oxygen therapy on severely ill patients’ prognosis and outcome.
Patients and methods This study was conducted on 70 adult severely ill patients admitted to Department of Critical Care, Alexandria Main University Hospital. The selected cases were divided into two groups: control group I included 35 patients who will receive conservative oxygen therapy, and study group II included 35 patients, who will receive liberal oxygen therapy.
Statistical analysis The collected data were coded, tabulated, and statistically analyzed using IBM statistical package for the social sciences statistics.
Results There was no significant difference between the two groups regarding demographic data, the incidence of shock, clinical data, the vital signs and hemodynamic data, laboratory data, the ICU mortality, the sequential organ failure assessment (SOFA) score, and ICU stay.
Discussion In our study, it was found that there was no significant difference between the outcome in the conservative oxygen therapy group and liberal oxygen therapy. This results may be owing to the small number of patients and the short duration of treatment.
Conclusion These results can be a starting point for further research studies assessing the potential beneficial effects of normoxia in critically ill patients.

Keywords: critically ill, oxygen therapy, oxygen toxicity


How to cite this article:
Abdelhady Mohamed WS. Comparative study of excessive oxygen therapy effects on critically ill patients’ outcome. Res Opin Anesth Intensive Care 2020;7:15-9

How to cite this URL:
Abdelhady Mohamed WS. Comparative study of excessive oxygen therapy effects on critically ill patients’ outcome. Res Opin Anesth Intensive Care [serial online] 2020 [cited 2020 Jun 2];7:15-9. Available from: http://www.roaic.eg.net/text.asp?2020/7/1/15/282599


  Introduction Top


Several years ago during a Respiratory Care Journal Conference on oxygen [1], Editor Emeritus Dr David Pierson quipped that ‘oxygen toxicity is like Bigfoot, everyone has heard of it, but nobody has actually seen it.’ The question of whether hyperoxia is a relevant clinical concern is problematic for several reasons. These include the complexity of tissue injury and related inflammatory processes, the effect of therapeutic interventions, and interindividual genetic variability. In addition, the issue is influenced by how the debate over hyperoxia has played out over the past 60 years, and that historical context continues to color contemporary perceptions and attitudes regarding the clinical importance of hyperoxia. Even now, when interest in ventilator-induced lung injury dominates the discussion of mechanical ventilation, the contributory role of hyperoxia is still considered to be of secondary importance [2].

Oxygen is one of the most commonly used drugs in acute medicine, yet its prescription and administration in clinical practice is poor [3]. The recognition that not only hypoxemia but also high fraction of inspired oxygen (FiO2) and hyperoxemia pose potential avoidable risks to patients has led to the concept of administering oxygen only if necessary to relieve hypoxemia, but at an FiO2 that does not lead to hyperoxemia [4]. In the antipodes, this management paradigm has been colloquially referred to as ‘swimming between the flags,’ in which oxygen is administered to keep the arterial oxygen saturation within a prespecified target range [5]. The efficacy of this approach was demonstrated in the landmark study of acute exacerbations of chronic obstructive pulmonary disease, in which oxygen administered if required to achieve an SpO2 between 88 and 92% reduced the risk of death by over twofold, as compared with a liberal oxygen regimen [6]. The question of whether conservative oxygen regimens reduce mortality risk in other critical illnesses has now been addressed in a recent systematic review and meta-analysis [7].

A lack of attentive oxygen management may expose patients unnecessarily to hyperoxia, leading to potential iatrogenic harm. In humans, direct lung toxicity is perhaps the best-known harmful consequence of hyperoxia with interstitial fibrosis, atelectasis, and tracheobronchitis [8]. Systemically, hyperoxia induces peripheral vasoconstriction and, in animal models, increases production of reactive oxygen species [8]. The PROXI trial (Perioperative Oxygen Fraction − effect on surgical site infection and pulmonary complications after abdominal surgery) reported an association between perioperative administration of a high FiO2 and an increase in long-term mortality [9]. Similarly, the recent AVOID trial (air vs. oxygen in myocardial infarction) showed that in patients with ST segment elevation myocardial infarction but without hypoxia, supplemental oxygen therapy may increase early myocardial injury and is associated with larger myocardial infarct size at 6 months [10]. Clinical uncertainty still surrounds the safety and benefit of hyperoxia after cerebral ischemia, out-of hospital cardiac arrest and cardiac surgery [11],[12].

Guidelines [5],[13] on the use of supplemental oxygen for various acute illnesses in adults are contradictory and inconsistent, and no high-quality evidence base exists. Moreover, although a number of randomized controlled trials comparing liberal versus conservative oxygen for various acute conditions have been done, the trial data have not been synthesized. Two previous systematic reviews [14] are illustrative, where both focused solely on patients with critical illness, but did not identify any relevant randomized controlled trials, and their meta-analyses of observational data were limited by considerable heterogeneity and risk of bias [15].

The incidence and severity of such harmful effects, the upper and lower oxygenation thresholds at which these harmful effects begin to occur, the interindividual variability in the physiological response to abnormal oxygen levels, the time-dependent and the dose-dependent characteristics of harmful effects, and their long-term safety data remain unclear. Just as the threshold for permissive hypoxemia is not clearly defined [16], the threshold for hyperoxia or hyperoxemia remains unclear too [15]. Furthermore, not only the oxygenation-related thresholds for potential injury may be different for different patients [17], they may vary with different stages of a disease in the same patient. It seems inaccurate to extrapolate these threshold levels from the observational studies, where outcomes could be influenced by many recognized or unrecognized cofounders. The bottom line is that the current state of knowledge is inadequate to recommend optimal oxygen targets among acutely ill patients. Therefore, it is imperative for the critical care research groups to lay the ground work for conducting well-designed trials that can address some of these basic questions about oxygen therapy.


  Aim of the work Top


This study was aimed to compare and evaluate the effects of excessive oxygen therapy on severely ill patients’ prognosis and outcome.


  Patients and methods Top


This study will be conducted on 70 adult severely ill patients admitted to Critical Care Department, Alexandria Main University Hospital.

Ethical considerations

The study was done after approval of ethical committee board of Faculty of Medicine, Alexandria University.

All cases were subjected to the following:
  1. History taking from the patient or next of kin including, age; sex; associated medical diseases, for example, cerebrovascular stroke, diabetes mellitus, cardiovascular disease, and renal disease; liver impairment; trauma; sepsis; cardiac arrest; emergency surgery; respiratory diseases or arterial hypertension; and drug history.
  2. Investigations including:


Continuous pulse oximetry, arterial blood gases when needed, and evaluation of all systems of the body will be done, and the severity of illness will be assessed by APACHE II score

Routine laboratory studies will be carried out on admission and followed up daily.

The selected cases were divided into two groups:
  • Control group I: 35 patients, who will receive conservative oxygen therapy.
  • Study group II: 35 patients, who will receive liberal oxygen therapy.


End points of the study

  1. Improvement and discharge from ICU.
  2. Death.


Outcome was judged by the following:
  1. SOFA score.
  2. Length of hospital and ICU stay.
  3. Disability and infection occurrence.


Statistical analysis

The collected data were coded, tabulated, and statistically analyzed using IBM statistical package for the social sciences statistics software, version 20.0 (2013; IBM Corp., Chicago, Illinois, USA). Descriptive statistics were done for quantitative data as minimum and maximum of the range as well as mean±SD for quantitative parametric data, whereas it was done for qualitative data as number and percentage.

Inferential analyses for independent variables were done using χ2 test for differences between proportions and Student’s t test for continuous variables.

The level of significance was taken as follows: P value less than 0.050 is highly statistically significant, otherwise it is nonsignificant.


  Results Top


A total of 70 patients were admitted to Critical Care Department. The patients were divided randomly into two groups as described previously. The basic characteristics of the studied patients are shown in [Table 1]. The demographic data (age and sex) showed insignificant difference between the two groups. The total mean of age was 59.6±11.9 years. The male patients were slightly increased than female patients, without significant difference. The clinical data of the patients in group I showed that 12 patients had shock (septic, hypovolemic, or cardiogenic), whereas 11 cases in group II had shock; there was no significant difference between the two groups regarding the incidence of shock. Liver and renal failure in the two groups was matched (five cases in each group). The documented infection in group I was noticed in three patients, whereas in group II, there were two patients who had infection. There was no significant difference between the two groups regarding clinical data.
Table 1 Characteristic of the patients in the two studied groups

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[Table 2] shows the hemodynamic and vital signs of the patients in the two groups. It was found that the vital signs and hemodynamic data of the two groups were matched in the two groups, without significant difference. Moreover, the laboratory data in [Table 3] showed insignificant difference between the two groups.
Table 2 Comparison between the two studied groups regarding hemodynamic and vital signs data

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Table 3 Comparison between the two studied groups regarding laboratory data

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The outcome at the end of study is described in [Table 4]. The ICU mortality (primary outcome) was 25.7% in group I and 20.0% in group II; although the mortality appears to be higher in group I, this increase was insignificant. Regarding secondary outcome, the incidence of infection in ICU stay period was 17.1% in group I and 11.4% in group II. On comparing the two groups, it was found that there was no significant difference between the two groups. The SOFA score in the two groups was similar without significant difference, and the ICU stay in the two groups was around 2 weeks with 10 days SD. There was no significant difference between the two groups regarding ICU stay ([Figure 1]).
Table 4 Comparison between the two studied groups regarding primary and secondary outcomes

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Figure 1 Comparison between the two studied groups regarding primary and secondary outcomes.

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  Discussion Top


Liberal oxygen use is still common. There is still uncertainty about the ideal target saturation, mostly owing to lack of evidence from clinical trials [18]. Most studies evaluating aiming for normoxia were performed at the ICU. Most ICU clinicians acknowledge the potential adverse effects of hyperoxia and declare low tolerance for high oxygen levels, but in clinical practice, a substantial number of their patients were exposed to high arterial oxygen levels [19]. Another ICU study found that hyperoxia was frequently observed but not resulted in adjustment of the ventilator settings [20]. This study’s main strength is that it is a prospective cohort study with inclusion of patients with different backgrounds.

In our study, it was found that there was no significant difference between the outcome in the conservative oxygen therapy group and liberal oxygen therapy. This result may be owing to the small number of patients and the short duration of treatment. This result was in disagreement with systemic review and meta-analysis study carried by Chu and colleagues. They concluded that in acutely ill adults, high-quality evidence shows that liberal oxygen therapy increases mortality without improving other patient-important outcomes. Supplemental oxygen might become unfavorable above an SpO2 range of 94–96%. These results support the conservative administration of oxygen therapy [21].

Education and feedback is needed to create more awareness of the importance of aiming for normoxia and applying this in clinical practice. Following the validation of the ideal target saturation, new guidelines for emergency oxygen therapy should be developed. To further assess primary and secondary outcome parameters, multicenter trials are required. Aiming for normoxia immediately after arrival in the hospital could prevent the potential harmful effects of hyperoxia, and this could lead to health gains on short and long term and reduced costs during hospital admission [22].This is a distinct viewpoint from the current observation that, at worst, liberal oxygen is not beneficial for acute illnesses [23]. Although the increased mortality risk with liberal oxygen therapy was too small to be conclusively detected in any single randomized controlled trial included in our systematic review, as a whole, the mean number needed to harm resulting in one death using a liberal approach is ∼71 (95% confidence interval, 37–1000). The magnitude of this effect is of major global public health importance [24] in view of the ubiquitous use of oxygen in acutely ill adults.


  Conclusion Top


These results can be a starting point for further research studies assessing the potential beneficial effects of normoxia compared with hyperoxia or hypoxia in critically ill patients and the subsequent development of guidelines.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

 
  References Top

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Kallet RH, Matthay MA. Hyperoxic acute lung injury. Respir Care 2013; 58:123–141.  Back to cited text no. 1
    
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Singhal AB, Benner T, Roccatagliata L, Koroshetz WJ, Schaefer PW, Lo EH et al. A pilot study of normobaric oxygen therapy in acute ischemic stroke. Stroke 2005; 36:797–802.  Back to cited text no. 11
    
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Gilbert-Kawai ET, Mitchell K, Martin D, Carlisle J, Grocott MP. Permissive hypoxaemia versus normoxaemia for mechanically ventilated critically ill patients. Cochrane Database Syst Rev 2014; 5:CD009931.  Back to cited text no. 16
    
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de Graaff AE, Dongelmans DA, Binnekade JM, de Jonge E. Clinicians’ response to hyperoxia in ventilated patients in a Dutch ICU depends on the level of FiO2. Intensive Care Med 2011; 37:46–51.  Back to cited text no. 20
    
21.
Chu D, Kim L, Young P, Zmiri N. Mortality and morbidity in acutely ill adults treated with liberal versus conservative oxygen therapy (IOTA): a systematic review and meta-analysis. Lancet 2018; 391:1693–1705.  Back to cited text no. 21
    
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    Figures

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    Tables

  [Table 1], [Table 2], [Table 3], [Table 4]



 

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Abstract
Introduction
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