Gastrointestinal hemodynamic changes during therapeutic hypothermia and after rewarming in neonatal hypoxic-Ischemic encephalopathy

Abstract

Background: Hypoxic-ischemic encephalopathy (HIE) is associated with disturbances in visceral blood flow velocities. Therapeutic Hypothermia (TH) is a standard of care; however, its impact on gastrointestinal blood flow in infants with HIE is unknown. The objective of this study was to assess gastrointestinal (GI) blood flow and left ventricle output (LVO) in infants with hypoxicischemic encephalopathy during whole body TH and after rewarming. Methods: Serial echocardiography and Doppler evaluation of intestinal blood flow (celiac (CA) and superior mesenteric (SMA) arteries) were prospectively performed in a cohort of 20 newborn infants with HIE at 4 time points during hypothermia and after rewarming. Demographic, clinical and biochemical data were collected and analyzed for their relevance. Results: Median gestational age and birth weight was 40 weeks (37e41) and 3410 g (2190 e4950) respectively. Celiac and mesenteric artery flow remained low during hypothermia and rose significantly after rewarming [peak systolic velocity in CA (0.63 m/s to 0.77 m/s, p Z 0.004) and SMA (0.43 m/s to 0.55 m/s, p Z 0.001)]. This increase was temporally associated with increased left ventricular output (106 ml/kg/min to 149 ml/kg/min, p < 0.0001).

Pathophysiology of Perinatal Asphyxia in Humans and Animal Models

“…Is important to note that LVO is lower in patients receiving therapeutic hypothermia (mean ± SD 126 ± 38 mL/kg/min), so one must be cautious interpreting it. Sakhuja et al [ 124 ] found that celiac artery and superior mesenteric artery blood flow velocity and LVO did not vary during hypothermia but rose after rewarming, suggesting a protective effect of therapeutic hypothermia on the gastrointestinal system [ 124 ].…”

Risk factors for early enteral nutrition feeding intolerance in neurocritical patients: A prospective case-control study

“…On the other hand, hypothermia therapy can lead to adverse effects such as gastrointestinal motility disorders, hypokalemia, stress hyperglycemia, pneumonia, and hypoalbuminemia [25]. Patients receiving hypothermia therapy have decreased, or absent bowel motility, and a higher incidence of gastric retention [26,27]. The present study showed that feeding intolerance during early enteral nutrition in patients treated with hypothermia therapy was 2.331 times higher than in patients without such therapy.…”

A Physiology-Based Pharmacokinetic Framework to Support Drug Development and Dose Precision During Therapeutic Hypothermia in Neonates

“…Celiac and mesenteric artery flow remained low during hypothermia with a significant increase after rewarming (peak systolic velocity celiac 0.63 to 0.77, + 22%; mesenteric 0.43 to 0.55 m/s. +28%), in line with a simultaneous increase in left ventricular output (106 to 149 ml/kg/min, +40%) (Sakhuja et al, 2019). Along the same line, bosentan absorption in critically ill neonates with pulmonary hypertension is delayed and steady state concentrations were only achieved from postnatal day 5 onwards (Steinhorn et al, 2016).…”

“…Males appear to be less resistant than females (Britton and Kline, 1945), and high body temperature also reduces resistance. In neonatal rats for example, it has been clearly shown that lowering the body temperature from 37 to 30°C during asphyxia has a protective effect (Saeed et al, 1993). Altricial species are more resistant to asphyxia than precocial TABLE 3 | Proposed experimental conditions for in vitro evaluation of the immediate versus delayed effects of hypothermia on activity of drug metabolizing enzymes (DME) and drug transporters (DT).…”