Pharmacological interventions for pain and sedation management in newborn infants undergoing therapeutic hypothermia

Bäcke, Pyrola; Bruschettini, Matteo; Sibrecht, Greta; Blomqvist, Ylva Thernström; Olsson, Eva‐Karin

doi:10.1002/14651858.cd015023.pub2

Cited by 10 publications

(7 citation statements)

References 81 publications

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“…Limited dosing information is currently available on drugs that are commonly administered to HIE neonates receiving TH [ 37 , 38 , 39 , 40 ]. Because of alterations in drug PKs, this vulnerable population requires unique clinical pharmacologic considerations [ 15 , 16 , 17 , 18 , 19 ].…”

Section: Discussionmentioning

confidence: 99%

“…Because of alterations in drug PKs, this vulnerable population requires unique clinical pharmacologic considerations [ 15 , 16 , 17 , 18 , 19 ]. HIE infants treated with TH require SA to improve both discomfort and pain from cooling, intubation, and mechanical ventilation [ 39 , 40 , 41 , 42 , 43 ]. To date, there are no standardized dosing guidelines for SA during TH [ 40 , 41 ].…”

Section: Discussionmentioning

confidence: 99%

“…HIE infants treated with TH require SA to improve both discomfort and pain from cooling, intubation, and mechanical ventilation [ 39 , 40 , 41 , 42 , 43 ]. To date, there are no standardized dosing guidelines for SA during TH [ 40 , 41 ]. Actually, the European hypothermia trial is the only one out of four earlier randomized controlled trials [ 2 , 3 , 4 , 36 , 37 ] to recommend a standard dose of morphine at 100 mg/kg every 4 h or in combination with fentanyl at equipotent doses.…”

Section: Discussionmentioning

confidence: 99%

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Continuous Fentanyl Infusion in Newborns with Hypoxic–Ischemic Encephalopathy Treated with Therapeutic Hypothermia: Background, Aims, and Study Protocol for Time-Concentration Profiles

Lugli,

Garetti,

Goffredo

et al. 2023

Biomedicines

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Therapeutic hypothermia (TH) is the standard of care for newborns with moderate to severe hypoxic–ischemic encephalopathy (HIE). Discomfort and pain during treatment are common and may affect the therapeutic efficacy of TH. Opioid sedation and analgesia (SA) are generally used in clinical practice, and fentanyl is one of the most frequently administered drugs. However, although fentanyl’s pharmacokinetics (PKs) may be altered by hypothermic treatment, the PK behavior of this opioid drug in cooled newborns with HIE has been poorly investigated. The aim of this phase 1 study protocol (Trial ID: FentanylTH; EUDRACT number: 2020-000836-23) is to evaluate the fentanyl time-concentration profiles of full-term newborns with HIE who have been treated with TH. Newborns undergoing TH receive a standard fentanyl regimen (2 mcg/Kg of fentanyl as a loading dose, followed by a continuous infusion—1 mcg/kg/h—during the 72 h of TH and subsequent rewarming). Fentanyl plasma concentrations before bolus administration, at the end of the loading dose, and 24-48-72-96 h after infusion are measured. The median, maximum, and minimum plasma concentrations, together with drug clearance, are determined. This study will explore the fentanyl time-concentration profiles of cooled, full-term newborns with HIE, thereby helping to optimize the fentanyl SA dosing regimen during TH.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Continuous Fentanyl Infusion in Newborns with Hypoxic–Ischemic Encephalopathy Treated with Therapeutic Hypothermia: Background, Aims, and Study Protocol for Time-Concentration Profiles

Lugli,

Garetti,

Goffredo

et al. 2023

Biomedicines

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“…We could not find other systematic reviews addressing the topic of our study. The protocol of a Cochrane review has been published, however it will include only randomized trials and a narrower list of drugs [35].…”

Section: Discussionmentioning

confidence: 99%

Interventions for the Management of Pain and Sedation in Newborns Undergoing Therapeutic Hypothermia for Hypoxic-Ischemic Encephalopathy: A Systematic Review

et al. 2022

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Background Newborn infants undergoing therapeutic hypothermia (TH) are exposed to multiple painful and stressful procedures. The aim of this systematic review was to assess benefits and harms of pharmacological and non-pharmacological interventions for the management of pain and sedation in newborn infants undergoing TH for hypoxic-ischemic encephalopathy. Methods We included randomized and observational studies reporting any intervention (either drugs or non-pharmacological interventions) to manage pain and sedation in newborn infants (> 33 weeks' gestational age) undergoing TH. We included any dose, duration and route of administration. We also included any type and duration of non-pharmacological interventions. Our prespecified primary outcomes were analgesia and sedation assessed using validated pain scales in the neonatal population; circulatory instability; mortality to discharge; and neurodevelopmental disability. A systematic literature search was conducted in the PubMed, Embase, CINAHL, Cochrane CENTRAL, Scopus, and Web of Science databases, with no language restrictions. Included studies underwent risk-of-bias assessment (Cochrane risk-of-bias tool and ROBINS-I) and data extraction performed by two authors independently. The plan had been to use effect measures such as mean difference for continuous outcomes and risk ratio for dichotomous outcomes, however the included studies are presented in a narrative synthesis due to their paucity and heterogeneity. Results Ten studies involving 3551 infants were included-one trial and nine observational studies. Most studies examined the use of phenobarbital or other antiepileptic drugs with primary outcomes related to seizure activity. The single trial that was included compared pentoxifylline with placebo. Among the primary outcomes, six studies reported circulatory instability and five reported mortality to discharge without relevant differences; two studies reported on neurodevelopmental disability and one study reported on pain scale. Three studies were ongoing. Conclusions We found limited evidence to establish the benefits and harms of the interventions for the management of pain and sedation in newborn infants undergoing TH. Long-term outcomes were not reported. Given the very low certainty of evidence-due to imprecision of the estimates, inconsistency and limitations in study design (all nine observational studies with overall serious risk of bias)-for all outcomes, clinical trials are required to determine the most effective interventions in this population. Systematic Review Registration PROSPERO registration number: CRD42020205755.

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“…Furthermore, it was found to decrease the time to extubation as well as the duration of mechanical ventilation [139]. It is worth noting that during the last several years, dexmedetomidine has attracted the interest of neonatologists as an analgesic/sedative agent in neonates undergoing therapeutic hypothermia due to its possible neuroprotective action [140,141] However, so far, there are insufficient data from randomized clinical trials evaluating the use of any analgesic-sedative agent during therapeutic hypothermia, including clonidine and dexmedetomidine [142]. Dexmedetomidine has been used in neonates at a starting dose of 0.2 to 0.3 mcg/kg/h, escalating in 0.1 mcg/kg/h increments depending on pain / sedation assessment scores, up to a median maximum dose of 0.5 mcg/kg/h (Table 3) [143].…”

Section: Alpha-2 Agonistsmentioning

confidence: 99%

Antibiotic Analgesic-Sedative and Antiseizure Medications Frequently Used in Critically Ill Neonates: A Narrative Review

Kontou,

Agakidou,

Chatziioannidis

et al. 2024

Preprint

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Several studies have shown that antibiotics, analgesic – sedative, and antiseizure medications are among the most commonly used medications in preterm and sick neonates. These infants are at high risk of developing nosocomial infections, central nervous system complications, and are exposed to numerous painful/stressful procedures. These severe, potentially life-threatening complications may have serious short- and long-term consequences and should be prevented and/or promptly treated. Previous studies and reviews have revealed significant variability in medications used in neonatal intensive care units (NICUs) worldwide, especially concerning the indications and dosages of first-line medications. This variability indicates the lack of adequate studies regarding the effectiveness and safety of these medications in neonates, especially the preterm ones. Important obstacles contributing to inadequate studies in preterm infants include difficulties in obtaining parental consent, physicians’ unwillingness to recruit preterm infants, the lack of license for use in neonates, and other scientific and ethical concerns. This review is an update on the use of antimicrobials – antifungals, analgesics – sedatives, and antiseizure medications used in neonates, focusing on existing evidence or knowledge gaps regarding their pharmacokinetics, indications, safety, dosage regimen (dose, dosing interval, route of administration), and evidence-based guidelines for the optimal use in neonates.

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Pharmacological interventions for pain and sedation management in newborn infants undergoing therapeutic hypothermia

Cited by 10 publications

References 81 publications

Continuous Fentanyl Infusion in Newborns with Hypoxic–Ischemic Encephalopathy Treated with Therapeutic Hypothermia: Background, Aims, and Study Protocol for Time-Concentration Profiles

Continuous Fentanyl Infusion in Newborns with Hypoxic–Ischemic Encephalopathy Treated with Therapeutic Hypothermia: Background, Aims, and Study Protocol for Time-Concentration Profiles

Interventions for the Management of Pain and Sedation in Newborns Undergoing Therapeutic Hypothermia for Hypoxic-Ischemic Encephalopathy: A Systematic Review

Antibiotic Analgesic-Sedative and Antiseizure Medications Frequently Used in Critically Ill Neonates: A Narrative Review

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