Randomised double-blind controlled trial of effect of morphine on catecholamine concentrations in ventilated pre-term babies

Quinn, Michael; Wild, Jennifer; Dean, H. G.; Hartley, R.; Rushforth, J.A.; Puntis, John; Levene, Malcolm I.

doi:10.1016/0140-6736(93)91472-x

Cited by 142 publications

(78 citation statements)

References 18 publications

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“…The routine use of narcotic analgesia, such as morphine or fentanyl, for heavy sedation of intubated infants (i.e. IPPV and HFOV) could have accounted for the partial alleviation of stress in ventilated infants (26,27). In addition, infants on nCPAP would not be sedated and were almost always prescribed caffeine for prevention of apnea and facilitation of respiration.…”

Section: Discussionmentioning

confidence: 99%

A Prospective Longitudinal Study to Estimate the “Adjusted Cortisol Percentile” in Preterm Infants

Wong

Chan

et al. 2011

Pediatr Res

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ABSTRACT:The normal range of serum cortisol concentrations and the appropriate levels of circulating cortisol in different clinical situations in preterm infants are not well defined. This study aimed to evaluate the impact of perinatal factors on circulating cortisol levels in preterm infants and to create a quantitative model that could estimate the "adjusted cortisol percentile." Serial serum cortisol concentrations were measured in 209 infants Յ32 wk gestation on d 1, 4, 7, 14, and 21 of life. Seven perinatal factors or conditions that could affect circulating cortisol level were identified. Serum cortisol levels were higher on d 4 (p ϭ 0. N ormal development of the hypothalamic-pituitary-adrenal (HPA) axis is essential for regulation of intrauterine homeostasis, timely maturation and differentiation of vital organ systems, and postnatal survival of newborns under stressful conditions (1,2). Over the past two decades, many reports have emphasized the importance of associations between circulating cortisol and systemic hypotension (3-5), bronchopulmonary dysplasia (BPD) (6 -8), and other stressful complications (9) in preterm and very LBW (VLBW) infants. It has been postulated that inadequate and low serum cortisol in these infants may be due to transient adrenal insufficiency of prematurity (i.e. "immature" intermediate enzyme systems in the steroidogenesis pathway resulting in insufficient cortisol production and with rapid recovery of the hormonal axis in early postnatal life) (5,10 -13) or relative adrenal insufficiency (i.e. failure to produce "appropriate quantity" of cortisol in response to stressful situations compared with the normal healthy subject of the same gestational and postnatal age) (6,8,11). The use of physiologic or therapeutic doses of systemic corticosteroids may be beneficial in these situations (3,4). However, the normal range of serum cortisol or what is considered to be the appropriate level of circulating cortisol in preterm infants is not known (14). More importantly, the effects of specific intrinsic (e.g. GA or postnatal age) and extrinsic factors (e.g. disease processes or treatment modalities) on the HPA axis have not been systematically evaluated (14). In the absence of such knowledge, meaningful interpretation of cortisol data is not possible. Furthermore, the use of systemic corticosteroids in infants with relatively normal or high levels of cortisol may expose the patients to unnecessary risks such as spontaneous intestinal perforation and should therefore be avoided. Previous studies investigating the response of the HPA axis to stress and serum cortisol in the postnatal period have many limitations. Some studies concentrated mainly on ventilated preterm infants (9,10), whereas the others monitored serum cortisol at only one or two timepoints (4,5,9,10) or performed the analysis of results as a secondary outcome of the original objective (9). Recently, we have also observed that a proportion of asymptomatic and unstressed VLBW infants who did not require mechanical ventila...

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Section: Discussionmentioning

confidence: 99%

A Prospective Longitudinal Study to Estimate the “Adjusted Cortisol Percentile” in Preterm Infants

Wong

Chan

et al. 2011

Pediatr Res

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“…Two retrospective studies evaluated the longterm effects of sedation or analgesia in preterm infants hospitalized in the NICU. The first study (104) evaluated neurologic outcome at 5-6 y in survivors from two randomized controlled trials, investigating morphine use in the early 1990s (105,106). No differences occurred between infants exposed and nonexposed to morphine, although the rates of death or disability in both groups were high (in the range of 40% for both), corresponding to commonly reported clinical outcomes in the presurfactant era.…”

Section: Existing Human Data On Neurotoxicity Of Sedative Drugs Used mentioning

confidence: 99%

Use of Analgesic and Sedative Drugs in the NICU: Integrating Clinical Trials and Laboratory Data

et al. 2010

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Recent advances in neonatal intensive care include and are partly attributable to growing attention for comfort and pain control in the term and preterm infant requiring intensive care. Limitation of painful procedures is certainly possible, but most critically ill infants require unavoidable painful or stressful procedures such as intubation, mechanical ventilation, or catheterization. Many analgesics (opioids and nonsteroidal anti-inflammatory drugs) and sedatives (benzodiazepines and other anesthetic agents) are available but their use varies considerably among units. This review summarizes current experimental knowledge on the effects of sedative and analgesic drugs on brain development and reviews clinical evidence that speaks for or against the use of common analgesic and sedative drugs in the NICU but avoids any discussion of anesthesia during surgery. Risk/benefit ratios of intermittent boluses or continuous infusions for the commonly used sedative and analgesic agents are discussed in the light of clinical and experimental studies. The limitations of extrapolating experimental results from animals to humans must be considered while making practical recommendations based on the currently available evidence.

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“…[1][2][3][4][5] Physiological responses to painful stimuli in the neonatal period are also reflected in hormonal, metabolic, and cardiorespiratory changes which are similar to those observed in adults.4 5 A potential factor affecting newborns' expression of pain is their state of alertness.1 6 In fact, sleeping newborns often cry less in response to sampling. Theoretically, we could reduce pain during normal invasive procedures by performing these during the sleep states, but this is impractical.…”

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confidence: 99%

Reduction of pain response in premature infants using intraoral sucrose.

Ramenghi

Wood

Griffith

et al. 1996

Archives of Disease in Childhood - Fetal and Neonatal Edition

110

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The potential ofsucrose to reduce the pain response in a group of healthy premature infants was investigated. Fifteen infants of 32-34 weeks postmenstrual age were tested in a blind crossover manner on two separate occasions no more than two days apart. Either 1 ml of 25% sucrose solution or sterile water was syringed into the baby's mouth 2 minutes before routine heel lancing. Response to the painful stimuli was measured by duration of cry and by facial expression (pain score).There was a significant reduction in the duration of first cry, the percentage of time spent crying in the 5 minutes after heel prick, and the pain score in the sucrose treated group. It is concluded that sucrose has analgesic effects in healthy premature infants. (Arch Dis Child 1996; 74: F126-F128) Keywords: analgesia, premature infant, sucrose, behavioural state, heel lance.The traditional view that newborns cannot feel pain has now been challenged. We know that newborns show a clinical behavioural response to a painful stimulus that is consistent with a more complex reflex nociceptive response. Crying is the primary method of communication in newborns and remains the most common clinical expression to measure their pain experience.Distinct facial expressions are also described as being associated with pain and have been objectively classified and often used to study nociception in neonates. 1-5Physiological responses to painful stimuli in the neonatal period are also reflected in hormonal, metabolic, and cardiorespiratory changes which are similar to those observed in adults. Studies demonstrating the antinociceptive effect of intraoral sucrose have, until now, been performed only on full term newborns. The aim of this study is to investigate the effects of oral sucrose on reducing the perception of pain in healthy preterm infants related to individual response to painful procedures. MethodsHealthy preterm infants, ranging in postmenstrual age between 32 and 34 weeks and postnatal age of more than 24 hours, who needed heel prick blood sampling for determination of glucose or bilirubin concentrations, were studied. They were in a stable medical condition and no infant had received either additional oxygen or sedation during the previous five days. The study was of a blind crossover design. Premature newborns were recruited if it was likely that they would require at least two heel prick blood sample within a period of no longer than 48 hours.Each baby was studied twice and was randomly allocated to receive either solution A (25% sucrose) or solution B (sterile water) on the first occasion; the alternative solution was given on the second occasion. The longest time interval between the two blood samplings was 48 hours, so that the effects on the anatomical and functional maturity of the baby would be comparable. The indication for blood sampling was the same (either BM stick test or serum bilirubin) for each of the paired tests in each baby. Each baby received either solution A or B before each one of the two blood samples, a...

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Randomised double-blind controlled trial of effect of morphine on catecholamine concentrations in ventilated pre-term babies

Cited by 142 publications

References 18 publications

A Prospective Longitudinal Study to Estimate the “Adjusted Cortisol Percentile” in Preterm Infants

A Prospective Longitudinal Study to Estimate the “Adjusted Cortisol Percentile” in Preterm Infants

Use of Analgesic and Sedative Drugs in the NICU: Integrating Clinical Trials and Laboratory Data

Reduction of pain response in premature infants using intraoral sucrose.

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