Abnormal Heart Rate Before Diagnosing Necrotizing Enterocolitis
Abnormal Heart Rate Before Diagnosing Necrotizing Enterocolitis
Objective: Earlier diagnosis and treatment of necrotizing enterocolitis (NEC) in preterm infants, before clinical deterioration, might improve outcomes. A monitor that measures abnormal heart rate characteristics (HRC) of decreased variability and transient decelerations was developed as an early warning system for sepsis. As NEC shares pathophysiologic features with sepsis, we tested the hypothesis that abnormal HRC occur before clinical diagnosis of NEC.
Study Design: Retrospective review of Bells stage II to III NEC cases among infants <34 weeks gestation enrolled in a prospective randomized clinical trial of HRC monitoring at three neonatal intensive care units.
Result: Of 97 infants with NEC and HRC data, 33 underwent surgical intervention within 1 week of diagnosis. The baseline HRC index from 1 to 3 days before diagnosis was higher in patients who developed surgical vs medical NEC (2.06±1.98 vs 1.22±1.10, P=0.009). The HRC index increased significantly 16 h before the clinical diagnosis of surgical NEC and 6 h before medical NEC. At the time of clinical diagnosis, the HRC index was higher in patients with surgical vs medical NEC (3.3±2.2 vs 1.9±1.7, P<0.001).
Conclusion: Abnormal HRC occur before clinical diagnosis of NEC, suggesting that continuous HRC monitoring may facilitate earlier detection and treatment.
Necrotizing enterocolitis (NEC) is the most common acquired intestinal disease of preterm infants, and despite advances in care in the neonatal intensive care unit (NICU), mortality may be as high as 30%. Survivors of NEC have longer hospital stay and are at risk for long-term nutritional and neurologic problems. A major challenge toward improving outcomes is identifying and treating infants in the early stages of NEC, when clinical signs may be subtle and nonspecific. Once more definitive signs appear, adverse outcomes such as extensive bowel necrosis leading to death or short bowel syndrome are more likely. Discovering markers of NEC that appear before overt clinical signs would facilitate earlier goal-directed therapies, which could improve outcomes.
Abnormal heart rate characteristics (HRC) have been established as a biomarker for late-onset neonatal sepsis and mortality in NICU patients. Our group has shown that reduced heart rate variability and transient decelerations often occur in the preclinical phase of sepsis. This finding inspired the development of a monitor that calculates an HRC index, a mathematical representation of decreased beat-to-beat variability and decelerations, which is the fold-increase in probability of sepsis being diagnosed in the next 24 h. In a recent randomized clinical trial (RCT) of 3003 infants, HRC monitoring reduced mortality in very low birth weight (VLBW) infants from 10.2 to 8.1%, a statistically significant and clinically meaningful result.
NEC and sepsis share pathophysiologic features, including a systemic inflammatory response, hemodynamic compromise and organ hypoperfusion. We and others have shown that elevated circulating levels of proinflammatory cytokines contribute to decreased heart rate variability. In NEC, serum cytokines are elevated, particularly when there is significant intestinal necrosis or associated bacteremia. Intestinal hypomotility, ileus and bowel distension have also been associated with increased vagal tone and altered HRC in adults. Our studies in preclinical models indicate that peritoneal administration of bacteria or fungi activates vagus nerve pathways leading to transient heart rate decelerations similar to those seen in neonates with sepsis. HRC changes may thus reflect activation of the cholinergic anti-inflammatory pathway, which has a critical role in host defense.
Abnormal HRC have not previously been studied in infants with NEC, and we therefore undertook a retrospective review of cases of NEC in VLBW infants during a prospective RCT of HRC monitoring. Our goal was to determine whether the HRC index could identify patients in the early, preclinical phase of disease when aggressive treatment may improve outcomes.
Abstract and Introduction
Abstract
Objective: Earlier diagnosis and treatment of necrotizing enterocolitis (NEC) in preterm infants, before clinical deterioration, might improve outcomes. A monitor that measures abnormal heart rate characteristics (HRC) of decreased variability and transient decelerations was developed as an early warning system for sepsis. As NEC shares pathophysiologic features with sepsis, we tested the hypothesis that abnormal HRC occur before clinical diagnosis of NEC.
Study Design: Retrospective review of Bells stage II to III NEC cases among infants <34 weeks gestation enrolled in a prospective randomized clinical trial of HRC monitoring at three neonatal intensive care units.
Result: Of 97 infants with NEC and HRC data, 33 underwent surgical intervention within 1 week of diagnosis. The baseline HRC index from 1 to 3 days before diagnosis was higher in patients who developed surgical vs medical NEC (2.06±1.98 vs 1.22±1.10, P=0.009). The HRC index increased significantly 16 h before the clinical diagnosis of surgical NEC and 6 h before medical NEC. At the time of clinical diagnosis, the HRC index was higher in patients with surgical vs medical NEC (3.3±2.2 vs 1.9±1.7, P<0.001).
Conclusion: Abnormal HRC occur before clinical diagnosis of NEC, suggesting that continuous HRC monitoring may facilitate earlier detection and treatment.
Introduction
Necrotizing enterocolitis (NEC) is the most common acquired intestinal disease of preterm infants, and despite advances in care in the neonatal intensive care unit (NICU), mortality may be as high as 30%. Survivors of NEC have longer hospital stay and are at risk for long-term nutritional and neurologic problems. A major challenge toward improving outcomes is identifying and treating infants in the early stages of NEC, when clinical signs may be subtle and nonspecific. Once more definitive signs appear, adverse outcomes such as extensive bowel necrosis leading to death or short bowel syndrome are more likely. Discovering markers of NEC that appear before overt clinical signs would facilitate earlier goal-directed therapies, which could improve outcomes.
Abnormal heart rate characteristics (HRC) have been established as a biomarker for late-onset neonatal sepsis and mortality in NICU patients. Our group has shown that reduced heart rate variability and transient decelerations often occur in the preclinical phase of sepsis. This finding inspired the development of a monitor that calculates an HRC index, a mathematical representation of decreased beat-to-beat variability and decelerations, which is the fold-increase in probability of sepsis being diagnosed in the next 24 h. In a recent randomized clinical trial (RCT) of 3003 infants, HRC monitoring reduced mortality in very low birth weight (VLBW) infants from 10.2 to 8.1%, a statistically significant and clinically meaningful result.
NEC and sepsis share pathophysiologic features, including a systemic inflammatory response, hemodynamic compromise and organ hypoperfusion. We and others have shown that elevated circulating levels of proinflammatory cytokines contribute to decreased heart rate variability. In NEC, serum cytokines are elevated, particularly when there is significant intestinal necrosis or associated bacteremia. Intestinal hypomotility, ileus and bowel distension have also been associated with increased vagal tone and altered HRC in adults. Our studies in preclinical models indicate that peritoneal administration of bacteria or fungi activates vagus nerve pathways leading to transient heart rate decelerations similar to those seen in neonates with sepsis. HRC changes may thus reflect activation of the cholinergic anti-inflammatory pathway, which has a critical role in host defense.
Abnormal HRC have not previously been studied in infants with NEC, and we therefore undertook a retrospective review of cases of NEC in VLBW infants during a prospective RCT of HRC monitoring. Our goal was to determine whether the HRC index could identify patients in the early, preclinical phase of disease when aggressive treatment may improve outcomes.
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