Randomised Trial of Fentanyl Anaesthesia in Preterm Babies Undergoing Surgery: Effects on the Stress Response

Anand, K.J.S.; Sippell, W.G.; Aynsley-Green, A

doi:10.1016/s0140-6736(87)91907-6

Cited by 527 publications

(187 citation statements)

References 20 publications

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“…Preterm infants spend, on average, 25 days in the neonatal intensive care unit (NICU), where they undergo 10-18 invasive procedures each day, including repeated heel lance, endotracheal intubation, surgery, and respiratory and gastric suctioning (www.marchofdimes.com/peristats/) [2,3,4]. Despite strong evidence that pain and stress circuitry are established and functional in preterm infants, 65% of these procedures are performed in the complete absence of analgesics [3,4,5,6,7]. Unfortunately, it is becoming increasingly clear that pain experienced during the critical perinatal developmental period has long-lasting effects on adult responses to pain-, anxiety- and stress-provoking stimuli [8,9,10].…”

Section: Introductionmentioning

confidence: 99%

A Single Neonatal Injury Induces Life-Long Deficits in Response to Stress

Victoria

Inoue²,

Young³

et al. 2013

Dev Neurosci

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Approximately 500,000 infants are born prematurely each year in the United States. These infants typically require an extensive stay in the neonatal intensive care unit (NICU), where they experience on average 14 painful and invasive procedures each day. These procedures, including repeated heel lance, insertion of intravenous lines, and respiratory and gastric suctioning, typically result in an inflammatory response, inducing pain and stress in the newborn. Remarkably, the majority of these procedures are performed in the complete absence of pre- or post-emptive analgesics. Recent clinical studies report that former NICU patients have increased thresholds for pain and stress later in life as compared with term-born infants. However, to date, the mechanisms whereby early-life inflammation alters later-life response to stress and pain are not known. The present studies were conducted to determine if neonatal injury impairs adult responses to anxiety- and stress-provoking stimuli. As we have previously reported that early-life pain results in a significant increase in opioid peptide expression within the midbrain periaqueductal gray, the role of endogenous opioids in our behavioral studies was also examined. Male and female rats received an intraplantar injection of the inflammatory agent carrageenan (1%) on the day of birth. In adulthood, animals were assessed for changes in response to anxiety- and stress-provoking stimuli using the open field and forced swim tests, respectively. Injury-induced changes in sucrose preference and stress-induced analgesia were also assessed. As adults, neonatally injured animals displayed a blunted response to both anxiety- and stress-provoking stimuli, as indicated by significantly more time spent in the inner area of the open field and a 2-fold increase in latency to immobility in the forced swim test as compared to controls. No change in sucrose preference was observed. Using in situ hybridization and immunohistochemistry, we observed a 2-fold increase in enkephalin mRNA and protein expression, respectively, in stress-related brain regions including the central amygdala and lateral septum. Administration of the opioid receptor antagonist naloxone reversed the attenuated responses to forced swim stress and stress-induced analgesia, suggesting the changes in stress-related behavior were opioid-dependent. Together, these data contribute to mounting evidence that neonatal injury in the absence of analgesics has adverse effects that are both long-term and polysystemic.

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Section: Introductionmentioning

confidence: 99%

A Single Neonatal Injury Induces Life-Long Deficits in Response to Stress

Victoria

Inoue²,

Young³

et al. 2013

Dev Neurosci

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“…Gut belegt sind dagegen die negativen Auswirkungen einer mangelhaften Schmerzausschaltung auf den postoperativen Verlauf [2] und auf das spätere Verhalten [15]. …”

Section: Was Ist Aus Der Experimentellen Forschung Bekannt?unclassified

Schädigt die Narkose das Gehirn von Kindern?

Jöhr

2006

Anaesthesist

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“…Es kommt zum Hypermetabolismus mit gesteigerter Glukogenolyse, Hyperglykämie und Hyperlaktämie sowie einem gesteigerten Stickstoffumsatz mit erhöhten Anteilen freier Fettsäuren im Plasma. Herzfrequenz und insbesondere pulmonalarterieller und intrakranieller Druck nehmen zu [6,50]. Im Gegensatz zum Erwachsenen weist dagegen der Blutdruck unter einer Stressreaktion nicht immer den typischen Anstieg auf.…”

Section: Ontogenese Des Opioidsystems Und Der Schmerzleitungunclassified

Schmerz und Opioide bei Neugeborenen und Säuglingen

Latasch

Freye

2002

Anaesthesist

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Despite the fact that neonates and infants are not capable of expressing their subjective pain sensations, it has become clear that they do perceive nociception, as pain correlates to hormonal, metabolic, immune, and cardiovascular changes. New findings support the notion that repetitive painful stimuli result in long term psycho-physiological effects with ensuing decreased attentiveness and orientation, poor regulation of behavioral state and motor processes, increase in irritability as well as an altered pattern of feeding and sleeping. These sequelae of repetitive painful experiences with an increase in sensitization of sensory afferent input supports the view of a sufficient analgesia during all kinds of painful procedures in the preterm and neonate. In order to sufficiently diminish nociceptive afferent input during surgery opioids are the drugs of choice aside from local anesthetics. However, the use of opioids in neonates and especially preterm infants must be considered in the light of certain pharmacokinetic and pharmacodynamic differences when compared to adults: 1. There is a longer elimination rate, which may result in post-operative overhang of respiratory depression, especially when opioids are given repetitively, resulting in an accumulation and an increased duration of action. 2. There is a reduced hepatic enzyme activity, which ultimately affects clearance rate. 3. The blood-brain-barrier is not fully developed in the preterm, which results in more access of opioids to binding sites in the CNS. 4. Differentiation of opioid-binding sites into mu, delta, and kappa has not reached its peak; thus, higher doses relative to body weight are needed to establish a sufficient deep plane of analgesia. 5. Caudal parts of the CNS, especially the pons-medullar region exhibit an earlier expression of receptors than the rostral parts. Sequelae of such differences are a more pronounced respiratory depression, often due to muscular rigidity, and bradycardia after which a full analgesic effect takes place. Despite such potential drawbacks, opioids are still the best choice as they sufficiently block nociceptive afferent input and when compared to other anesthetics, they show the least cardiovascular changes. One, however, has to bear in mind that dosing is done according to effect and not to body weight while potential side effects are most prominent in the preterm infant.

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Randomised Trial of Fentanyl Anaesthesia in Preterm Babies Undergoing Surgery: Effects on the Stress Response

Cited by 527 publications

References 20 publications

A Single Neonatal Injury Induces Life-Long Deficits in Response to Stress

A Single Neonatal Injury Induces Life-Long Deficits in Response to Stress

Schädigt die Narkose das Gehirn von Kindern?

Schmerz und Opioide bei Neugeborenen und Säuglingen

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