Effects of nociceptive stimuli on the pulmonary circulation in the ovine fetus

Abstract

The fetus is able to exhibit a stress response to painful events, and stress hormones have been shown to modulate pulmonary vascular tone. At birth, the increased level of stress hormones plays a significant role in the adaptation to postnatal life. We therefore hypothesized that pain may alter pulmonary circulation in the perinatal period. The hemodynamic response to subcutaneous injection of formalin, which is used in experimental studies as nociceptive stimulus, was evaluated in chronically prepared, fetal lambs. Fetal lambs were operated on at 128 days gestation. Catheters were placed into the ascending aorta, superior vena cava, and main pulmonary artery. An ultrasonic flow transducer was placed around the left pulmonary artery. Three subcutaneous catheters were placed in the lambs' limb. The hemodynamic responses to subcutaneous injection of formalin, to formalin after fetal analgesia by sufentanil, and to sufentanil alone were recorded. Cortisol and catecholamine concentrations were also measured. Pulmonary vascular resistances (PVR) increased by 42% (P Ͻ 0.0001) after formalin injection. Cortisol increased by 54% (P ϭ 0.05). During sufentanil infusion, PVR did not change significantly after formalin. Cortisol increased by 56% (P Ͻ 0.05). PVR did not change during sufentanil infusion. Norepinephrine levels did not change during any of the protocols. Our results indicate that nociceptive stimuli may increase the pulmonary vascular tone. This response is not mediated by an increase in circulating catecholamine levels. Analgesia prevents this effect. We speculate that this pulmonary vascular response to nociceptive stimulation may explain some hypoxemic events observed in newborn infants during painful intensive care procedures. experimental pain animal model; fetal pain; fetal analgesia; pulmonary vascular reactivity; stress hormones THE DEVELOPMENT OF FETAL INVASIVE procedures and a better knowledge about pain in preterm and full-term newborn infants have led to increased interest in the subject of fetal pain. Nociception during early development is poorly understood. However, numerous indirect evidence such as behavioral or neurohormonal responses to invasive procedures suggests that the fetus can feel pain very early in gestation (17,18,20). Fetal brain-sparing response has been observed after procedures involving transgression of fetal trunk from as early as 16 wk (54). Furthermore, transfusion through the intrahepatic veins is associated with substantial rises in stress hormones (norepinephrine, cortisol, ␤-endorphin) from as early as 18 wk of gestation (17,18).At birth, the increase in stress hormones plays a significant role in the adaptation to postnatal life, including increased left ventricular contractility, lung fluid reabsorption, and surfactant release (11,25,35,47,49,60). Stress hormones have also been shown to modulate the pulmonary vascular tone and reactivity during the perinatal life (12,26,29). These data suggest that perinatal stress may alter the pulmonary circulation. Furthermore, hyp...

Review shows that implementing a nationwide protocol for congenital diaphragmatic hernia was a key factor in reducing mortality and morbidity

“…Many environmental factors may worsen PPHN. Stress and pain increase pulmonary vascular resistance by activating alpha one adrenergic receptors . Stress factors, such as noise, tactile stimulation, tracheal suctioning and heel pricks, must only be carried out when it is strictly necessary.…”

“…The benefits of using, or not using, postoperative pleural drains have not been demonstrated. Optimal analgesia based on the use of a validated newborn pain scale is necessary to prevent pulmonary hypertension .…”

Prostaglandin E1 in infants with congenital diaphragmatic hernia (CDH) and life-threatening pulmonary hypertension

“…Additional measurements would have provided further meaningful evidence to explain the effects of PGE1. However, extensive Doppler echographic assessment may induce stress and pain, which in turn may worsen pulmonary hypertension (25,26).…”

Prise en charge médicale per- et postnatale de la hernie congénitale diaphragmatique

“…Le stress et la douleur augmentent les RVP par activation des récepteurs 1 -adrénergiques [43,47]. Les facteurs de stress -bruit, stimulation tactile, aspiration trachéale, piqûre au talon, etc.…”