Key messages
1. Dexmedetomidine is a medicine that is used to relieve pain and induce sleep. It is used in newborn babies who need mechanical ventilation (a machine to assist breathing). We found no evidence to support using or not using dexmedetomidine in newborn babies on mechanical ventilation.
2. Well-designed studies are needed to determine the benefits and harms of dexmedetomidine in newborn babies, particularly in very preterm babies, as they are the sickest.
What is dexmedetomidine?
Dexmedetomidine is a sedative. Sedatives work by helping a person to relax and feel calm; often people fall asleep after taking a sedative. Dexmedetomidine also has pain relief properties. Dexmedetomidine is given to people of all ages to help them relax and feel less pain during intensive care, mechanical ventilation, and stressful diagnostic or surgical procedures.
Why is this important for newborn babies who are on mechanical ventilation?
About 9% of all newborns are admitted to a neonatal intensive care unit (NICU) directly after birth. Many of these infants require help breathing and are on mechanical ventilators. Mechanical ventilation and time in the NICU are stressful for babies. Pain and stress in newborns lead to long-lasting complications (into adulthood). Medicines to relieve pain and reduce stress are therefore often needed during intensive care.
To reduce the pain and stress associated with ventilators, infants are usually given pain relief medicines like opioids (morphine, fentanyl) combined with midazolam. Midazolam is a benzodiazepine (sedative) and helps to relax the baby. Morphine and fentanyl both have serious side effects such as physical dependency, withdrawal problems, and slowed digestion and breathing.
Dexmedetomidine may be used in place of opioids and benzodiazepines, or in combination with smaller doses of opioids. Dexmedetomidine does not affect respiratory drive (the infant does not forget to breathe), simplifying assistance during kangaroo care (skin-to-skin contact).
What did we want to find out?
We wanted to find out if dexmedetomidine is an effective and safe medicine to use for pain and stress relief in sick newborn babies who need mechanical ventilation.
What did we do?
We searched for studies that looked at dexmedetomidine compared with opioids (such as morphine or fentanyl), non-opioid relaxing medicines (such as ketamine, midazolam, phenobarbital, or propofol), or placebo (dummy treatment) in sick newborns in need of mechanical ventilation.
What did we find?
We did not find any studies comparing dexmedetomidine with relaxing medicines or placebo. We found four ongoing studies comparing dexmedetomidine with fentanyl, morphine, and ketamine plus dexmedetomidine. We are unsure if these studies will help answer the question about using dexmedetomidine for pain relief and sedation in babies on mechanical ventilation, because we do not yet know if the babies in the studies will need mechanical ventilation.
What are the limitations of the evidence?
We did not find evidence to support using or not using dexmedetomidine to reduce pain and discomfort in preterm infants on mechanical ventilation.
How up to date is this evidence?
The evidence is current to September 2023.
Despite the increasing use of dexmedetomidine, there is insufficient evidence supporting its routine use for analgesia and sedation in newborn infants on mechanical ventilation. Furthermore, data on dexmedetomidine safety are scarce, and there are no data available on its long-term effects.
Future studies should address the efficacy, safety, and long-term effects of dexmedetomidine as a single drug therapy for sedation and analgesia in newborn infants.
Dexmedetomidine is a selective alpha-2 agonist with minimal impact on the haemodynamic profile. It is thought to be safer than morphine or stronger opioids, which are drugs currently used for analgesia and sedation in newborn infants. Dexmedetomidine is increasingly being used in children and infants despite not being licenced for analgesia in this group.
To determine the overall effectiveness and safety of dexmedetomidine for sedation and analgesia in newborn infants receiving mechanical ventilation compared with other non-opioids, opioids, or placebo.
We searched CENTRAL, MEDLINE, Embase, CINAHL, and two trial registries in September 2023.
We planned to include randomised controlled trials (RCTs) and quasi-RCTs evaluating the effectiveness of dexmedetomidine compared with other non-opioids, opioids, or placebo for sedation and analgesia in neonates (aged under four weeks) requiring mechanical ventilation.
We used standard Cochrane methods. Our primary outcomes were level of sedation and level of analgesia. Our secondary outcomes included days on mechanical ventilation, number of infants requiring additional medication for sedation or analgesia (or both), hypotension, neonatal mortality, and neurodevelopmental outcomes. We planned to use GRADE to assess the certainty of evidence for each outcome.
We identified no eligible studies for inclusion.
We identified four ongoing studies, two of which appear to be eligible for inclusion; they will compare dexmedetomidine with fentanyl in newborn infants requiring surgery. We listed the other two studies as awaiting classification pending assessment of full reports. One study will compare dexmedetomidine with morphine in asphyxiated newborns undergoing hypothermia, and the other (mixed population, age up to three years) will evaluate dexmedetomidine versus ketamine plus dexmedetomidine for echocardiography. The planned sample size of the four studies ranges from 40 to 200 neonates. Data from these studies may provide some evidence for dexmedetomidine efficacy and safety.