Inadequate Oxygen Delivery Dose and Major Adverse Events in Critically Ill Children With Sepsis

Katie L. Roy, DNP; Anna Fisk, PhD; Peter Forbes, MA; Conor C. Holland, BEng; Sara R. Schenkel, MPH; Sally Vitali, MD; Michele DeGrazia, PhD

Disclosures

Am J Crit Care. 2022;31(3):220-228. 

In This Article

Abstract and Introduction

Abstract

Background: The inadequate oxygen delivery (IDO 2) index is used to estimate the probability that a patient is experiencing inadequate systemic delivery of oxygen. Its utility in the care of critically ill children with sepsis is unknown.

Objective: To evaluate the relationship between IDO 2 dose and major adverse events, illness severity metrics, and outcomes among critically ill children with sepsis.

Methods: Clinical and IDO 2 data were retrospectively collected from the records of 102 critically ill children with sepsis, weighing >2 kg, without preexisting cardiac dysfunction. Descriptive, nonparametric, odds ratio, and correlational statistics were used for data analysis.

Results: Inadequate oxygen delivery doses were significantly higher in patients who experienced major adverse events (n = 13) than in those who did not (n = 89) during the time intervals of 0 to 12 hours (P < .001), 12 to 24 hours (P = .01), 0 to 24 hours (P < .001), 0 to 36 hours (P < .001), and 0 to 48 hours (P < .001). Patients with an IDO 2 dose at 0 to 12 hours at or above the 80th percentile had the highest odds of a major adverse event (odds ratio, 23.6; 95% CI, 5.6- 99.4). Significant correlations were observed between IDO 2 dose at 0 to 12 hours and day 2 maximum vasoactive inotropic score (ρ= 0.27, P = .006), day 1 Pediatric Logistic Organ Dysfunction (PELOD-2) score (ρ = 0.41, P < .001), day 2 PELOD-2 score (ρ= 0.44, P < .001), intensive care unit length of stay (ρ= 0.35, P < .001), days receiving invasive ventilation (ρ= 0.42, P < .001), and age (ρ= −0.47, P < .001).

Conclusions Routine IDO 2 monitoring may identify critically ill children with sepsis who are at the highest risk of adverse events and poor outcomes.

Introduction

Sepsis is a common cause of pediatric morbidity and mortality around the world, with an estimated 1.2 million cases of pediatric sepsis and 3 million cases of neonatal sepsis per year.[1,2] In the United States, sepsis-associated mortality may reach 30% among children with septic shock who require intensive care.[2,3] Morbidity is similarly substantial. Among a sample of critically ill children with community-acquired septic shock, 35% of survivors had not regained their baseline health-related quality of life after 1 year.[4]

Given such devastating effects, the World Health Organization has recognized reducing sepsis as a global health priority and has adopted a resolution urging the pursuit of technologically innovative research to support sepsis management.[5,6] An emerging and promising prospect in this regard is the arena of predictive analytics. The inadequate oxygen delivery (IDO2) index is a predictive algorithm developed by Etiometry Inc that synthesizes physiological and laboratory measures to estimate the probability that a patient is experiencing inadequate systemic delivery of oxygen (DO2).[7]

In shock states, such as septic shock, an imbalance between DO2 and oxygen consumption portends tissue hypoxia and organ dysfunction.[8] Venous oxygen saturation (SVO2) and central venous oxygen saturation (SCVO2) serve as indicators of this balance.[8] Although guidelines for sepsis management in adults no longer recommend targeted SCVO2 therapy in the context of early goal-directed therapy amid a lack of supportive evidence, some pediatric studies have demonstrated the value of targeted SCVO2 therapy in reducing mortality.[9–11] Sankar et al[10] found that among children with septic shock and low SCVO 2 at admission, only those in whom this value normalized to greater than 70% within the first 6 hours survived. Tools that continuously reflect SCVO 2 or SVO 2, such as the IDO 2 index, may allow early and ongoing risk stratification of children with sepsis and septic shock.

The IDO2 index has been approved as a medical device by the US Food and Drug Administration for use in postsurgical patients aged 0 to 12 years with weight greater than 2 kg.[7] The utility of the IDO2 index in patients older than 12 years has yet to be determined but deserves examination. Investigation of its applicability to those with sepsis is also warranted, as insufficient DO2 is a critical determinant of sepsis-associated tissue hypoperfusion. Minimum data required for the IDO2 index are heart rate every 60 seconds, oxygen saturation via pulse oximetry every 10 minutes, and arterial blood pressure every 10 minutes. If data are available, the algorithm will also use arterial oxygen saturation, SVO2, hemoglobin level, temperature, regional oxygenation, and filling pressures.[7]

Patient data are collected by Etiometry's T3 Data Aggregation and Visualization software and then filtered through the IDO2 algorithm (Figure 1). The algorithm uses a software model of human physiology and estimation theory to compute the likelihood that SVO2 is below a particular level, typically 40%.[7] Values of the IDO2 index range from 0 to 100, with higher values indicating greater risk that the patient's SVO2 is below the selected level.[7] The IDO 2 index values are computed every 5 seconds and can be displayed in real time at the bedside, providing an advantage over intermittent SCVO 2 or SVO 2 levels, which require central venous access for collection. The IDO 2 dose is calculated retrospectively and is an average of all IDO 2 index values over a specified time interval.

Figure 1.

Flowchart of IDO 2 algorithm with graph of IDO 2 values. Red peaks indicate greater patient risk of SVO 2 below the selected level.
Abbreviations: IDO 2, inadequate oxygen delivery; SaO 2, arterial oxygen saturation; SpO 2, oxygen saturation as measured by pulse oximetry; SVO 2, venous oxygen saturation.

To date, the IDO2 index has been used primarily in pediatric cardiac surgery patients, who may have limited ability to increase cardiac output and systemic DO2 in response to increased oxygen demand.[12] Single-ventricle and mixing lesions may similarly result in obligate arterial desaturation with reduced DO2 and SVO2.[12,13] A recent study by Dewan et al,[14] however, demonstrated good performance of the IDO 2 index in a general pediatric intensive care unit (PICU) sample in which the IDO 2 index indicated the probability that SVO 2 was below the level of 50%, instead of 40%. The 50% level may serve to enhance the sensitivity of the IDO 2 index among noncardiac populations.

The purpose of this retrospective study was to evaluate the relationship between IDO 2 dose during the first 48 hours of admission to the PICU and major adverse events (MAEs), illness severity metrics, and outcomes among critically ill children with sepsis, severe sepsis, or septic shock. In this study, IDO 2 dose indicated the probability that SVO 2 was below the level of 50%. We calculated IDO 2 doses for 4 discrete time intervals: 0 to less than 12 hours, 12 to less than 24 hours, 24 to less than 36 hours, and 36 to less than 48 hours (hereinafter referred to as 0–12, 12–24, 24–36, and 36–48 hours). We also calculated IDO 2 doses for 4 cumulative time intervals: 0 to less than 12 hours, 0 to less than 24 hours, 0 to less than 36 hours, and 0 to less than 48 hours (hereinafter referred to as 0–12, 0–24, 0–36, and 0–48 hours). Major adverse events were defined as cardiac arrest requiring chest compressions, extracorporeal membrane oxygenation (ECMO) cannulation, and all-cause 28-day mortality. Illness severity metrics included maximum vasoactive-inotropic score (VIS) and organ dysfunction as measured by the Pediatric Logistic Organ Dysfunction version 2 (PELOD-2) score.[15–18] Outcomes included PICU length of stay (LOS) and days receiving invasive ventilation.

Study patients were <18 years of age with an admission diagnosis of sepsis, severe sepsis, or septic shock.

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