Key messages

• Studies used different scales to measure how well midazolam calms infants in intensive care. Only one study used a validated scale.

• It is uncertain if midazolam calms babies, reduces pain, affects blood pressure or breathing, or changes long-term brain development.

• Currently, we do not have enough evidence to support the use of midazolam in babies, especially preterm babies.

What is sedation?

Sedation is a medical treatment that helps people feel calm, sleepy, or unaware during a procedure. In newborn babies, sedation may be needed for tests or treatments that could cause stress or pain.

Why is sedation important for babies in intensive care?

Babies in the neonatal intensive care unit often need tests and treatments that may be uncomfortable or painful. Proper sedation may help reduce stress and discomfort during procedures, immediate medical problems like changes in blood pressure or bleeding in the brain, and long-term effects on the brain such as learning and thinking difficulties later in life.

What is midazolam, and how does it work?

Midazolam is a medicine from the benzodiazepine family. It works by slowing down brain activity, which can help reduce anxiety and make a person feel relaxed, sleepy, or unaware of their surroundings. Midazolam is sometimes used to help newborn babies stay calm and comfortable during medical procedures, especially when they are connected to a breathing machine or having a scan such as magnetic resonance imaging (MRI). Midazolam is usually given through a vein, but can also be given in other ways, such as through the nose.

What other medicines and methods can be used for keeping newborns calm and comfortable?

Other options to help calm or comfort newborns include methods like swaddling or skin-to-skin contact, or giving small amounts of sweet solutions by mouth. Medicines such as opioids can help with pain, while others like clonidine and dexmedetomidine may provide calming effects without affecting breathing too much. Propofol and phenobarbital are also sometimes used, depending on the baby's condition and medical needs.

What did we want to find out?

We wanted to find out whether midazolam is helpful and safe for sedating babies in the neonatal intensive care unit. Specifically, we wanted to know whether:

• midazolam helps babies stay calm and still during procedures or while on a breathing machine;

• babies who receive midazolam show fewer signs of pain, such as crying or changes in heart rate;

• using midazolam affects how the baby's brain works as they grow older, including things like memory, problem-solving, movement, and how they interact with others;

• midazolam causes unwanted effects, such as hypotension (drops in blood pressure), apnoea (pause in breathing) or serious complications;

• midazolam reduces the risk of babies dying in hospital;

• midazolam reduces the time babies have to be on a breathing machine.

What did we do?

We searched for studies comparing midazolam with other sedation methods, such as:

• placebo (a substance with no medical effect);

• methods that don't involve giving medicine, such as non-nutritive sucking, skin-to-skin contact, swaddling, or massage;

• sweet solutions such as sucrose or glucose, given by mouth;

• pain-killing medicines such as opioids (morphine, fentanyl); and

• other medicines such as clonidine, dexmedetomidine, propofol, or phenobarbital.

We then summarised the results and rated how confident we were in the findings.

What did we find?

We included six studies with 388 babies, of whom 184 received midazolam. The babies were sedated before being put on a breathing machine or having an MRI scan. The studies compared midazolam with placebo, opioids (morphine, fentanyl), oral sweet solutions, and phenobarbital.

Main results

• We are very unsure about the effect of midazolam compared with placebo on low blood pressure (1 study, 46 babies), interrupted breathing (1 study, 33 babies), death (3 studies, 122 babies), and days on ventilation (2 studies, 89 babies). No studies comparing these treatments measured pain relief or brain development.

• We are very unsure about the effect of midazolam compared with opioids on the time babies spend on ventilators (2 studies, 106 babies), low blood pressure and interrupted breathing (1 study, 60 babies), and death (1 study, 46 babies). No studies comparing these treatments measured sedation, pain relief, or brain development.

• We are very unsure about the effect of midazolam compared with oral sweet solutions on interrupted breathing (1 study, 112 babies). No studies comparing these treatments measured sedation, pain relief, brain development, low blood pressure, death, or days on ventilation.

We found no studies comparing midazolam with methods that don't involve giving medicine, such as swaddling or massage.

What are the limitations of the evidence?

We found only a few studies. Some included studies were small, used different doses or ways of giving midazolam, and did not report key results like pain relief or effects on brain development. Furthermore, only one study used a validated tool (proven to give reliable results) to measure how effectively the babies were sedated. Because of these limitations, we cannot say with confidence whether midazolam is effective or safe for newborns in neonatal intensive care.

How up to date is this evidence?

The evidence is current to 23 January 2025.