Significance of gastroesophageal refluxate in relation to physical, chemical, and spatiotemporal characteristics in symptomatic intensive care unit neonates

Abstract

Gastroesophageal reflux disease (GERD) is a frequent consideration in intensive care unit neonates. We tested the hypothesis that symptoms in GERD are dependent on the spatiotemporal and physicochemical characteristics of reflux events by evaluating the symptom sensitivity index (SSI) and symptom index (SI) in relation to the refluxate characteristics. Thirty symptomatic neonates (30.7 ± 0.8 wk gestation) were evaluated using manometry and pH-impedance methods. During 704.3 h of recordings, 2063 gastroesophageal reflux (GER) were observed; 54% of the GER were associated with symptoms. Defined by physical characteristics, there were 51.3% liquid, 29.1% gas, and 19.6% mixed GER. Defined by chemical characteristics, there were 48.5% acid and 51.5% nonacid GER. Defined by most proximal extent, 79.2% were supra-UES (upper esophageal sphincter) and 20.8% were infra-UES. Higher SSI was noted with pH-only events (p < 0.0001 versus pH-impedance events). Higher SI was noted with movement symptoms (versus sensory, p = 0.04). In a subset analysis, the frequencies of GER events, acid clearance time, and SSI were all greater in chronic lung disease versus none (p < 0.001). In conclusion, clinical significance of symptoms as measured by SSI and SI and characterization of spatial-temporal-physical-chemical nature of GER events as defined by pH-impedance methods clarifies the definition of GERD.

Fig. 1. Duration of average BCT and average ACT per patient per GER event

In A), average BCT is different based on physical (liquid vs. mixed, *P=0.0002), and spatial characteristics (high vs. low, ‡P=0.0001) but similar based on chemical characteristics (acid vs. non-acid, P=NS). In B), average ACT is longer for pH-only events compared to acid pH-impedance events (**p<0.0001). The boundary of the box indicates the 25^th and 75^th percentiles; the solid line within the box marks the median value; and the error bars indicate the 5^th and 95^th percentiles.

Fig. 2. Physico-chemical composition of GER defined as supra-UES or infra-UES

In A), significant difference is noted with the distribution of GER based on physical properties, infra- vs. supra-UES (*P<0.0001). Mixed GER is represented in white, liquid in gray, and gas in black. In B), significant difference is noted with the distribution of GER based on chemical properties, between infra- vs. supra-UES (*P<0.0001). NARE and ARE are represented in white and black respectively.

Fig. 3. Distribution of SI and SSI

The dotted lines indicate the thresholds for the SSI (positive if >10%; horizontal line) and the SI (positive if >50%; vertical line). Note the discordance between the SI and the SSI in many patients.

Fig. 4. Symptom distribution based on physico-chemical characteristics

In A), symptom distribution based on physical properties: gas vs. liquid (*p<0.0001); gas vs. mixed (§p=0.0008); liquid vs. mixed (¶p=0.05). In B), symptom distribution based on chemical properties: acid vs. non-acid (**p=0.001). Respiratory-, sensory- and movement- symptoms are represented in white, gray and black respectively.

Fig. 5. Relationship of symptoms/reflux with esophageal ACT and BCT

are shown in 5A (P<0.0001 for association) and 5B (P=0.01 for association) respectively.