"Can you explain the difference between dexamethasone and hydrocortisone for extubation?"

I received a great question the other day asking about the difference between steroids to facilitate extubation in the NICU. Hydrocortisone and Dexamethasone are both corticosteroids that can help facilitate extubation, but how do they work, what are the risks, and how does the medical team determine which steroid to give? Let’s review the evidence together. 

Bronchopulmonary dysplasia (BPD) remains the most common morbidity of prematurity, affecting thousands of infants annually in the United States. BPD is a developmental disruption in lung growth and maturation. It manifests with decreased oxygenation, as well as increased work of breathing and susceptibility to pathogens and environmental factors. Two of the major factors that contribute to BPD are inflammation and mechanical ventilation, thus corticosteroids may be prescribed in an attempt to facilitate extubation and reduce pulmonary inflammation.

Pathophysiology

Before we dive into steroids, let's make sure we're all on the same page about BPD. If you've been in the NICU for a while, you've definitely seen it, but do you feel like you understand what's happening inside the lungs?

BPD occurs due to multiple factors including interrupted lung development, inflammation and lung injury due to mechanical ventilation. 

The "Multi-Hit" Theory

Here's what I want you to remember for your RNC-NIC exam: BPD isn't caused by just one thing. It's what we call a "multi-hit" process:

• Hit #1: Baby is born early because of infection, preeclampsia, or other complications

• Hit #2: Immature lungs undergo injury due to mechanical ventilation

• Hit #3: Oxygen exposure creates free radical damage

• Hit #4: Maybe the baby gets an infection or develops NEC ☹️(which causes MORE inflammation)

• Hit #5: More ventilator time, more inflammation...

Each "hit" makes BPD more likely, and unfortunately, many of our tiniest babies experience multiple hits.

RNC-NIC Tip: Remember that BPD is defined as needing supplemental oxygen at 28 days of life OR at 36 weeks postmenstrual age, depending on which definition your unit uses.

Yu et al, 2024

Why Do We Use Steroids for BPD?

Great question! Here's the thing—inflammation is a HUGE part of what drives BPD development. When we can reduce that inflammation in the lungs, we often see:

✅ Easier time weaning from the ventilator
✅ Less oxygen requirement
✅ Better lung compliance
✅ Reduced risk of severe BPD

Think of steroids as powerful anti-inflammatory medications that can help break the cycle of lung injury and inflammation.

Sounds great, right? So why is there hesitancy? Steroids have been known to reduce inflammation since the 1980s BUT further research found that the babies who received prolonged high doses of dexamethasone (especially early in life) had worse developmental outcomes (cerebral palsy, neurosensory disability, and poor growth). In the early 2000s, the AAP had a policy statement stating we should not routinely prescribe postnatal steroids.

A lot has changed since then. Smaller and smaller babies are surviving and BPD is still a major issue. More studies have been completed and the AAP has revised their statement (in 2010 then again in 2022) stating that postnatal corticosteroids cannot be routinely recommended and the decision to use corticosteroids to prevent or treat BPD must be individualized.

Individualizing Treatment: Who Should Get Steroids?

This is probably one of the most important and difficult questions. The research gives us some guidance, but every baby (and NICU) is different.

The Risk vs the Benefit

The baseline risk of BPD in your patient population matters.

• Low baseline BPD risk (<33%): Using steroids actually increases the risk of death or cerebral palsy.

• High baseline BPD risk (>60%): Steroids reduce the combined outcome of death or cerebral palsy. 

So what does this mean for your NICU? Your team needs to identify babies who are at high risk for developing moderate-to-severe BPD. How do we do that?

Using the Neonatal BPD Outcome Estimator

Clinical Pearl: There's a fantastic tool called the Neonatal BPD Outcome Estimator that can help you calculate a baby's risk of BPD at various time points.

The Clinical Decision-Making Process

The evidence-based threshold of 60% moderate-to-severe BPD risk isn't always straightforward to apply because BPD risk actually decreases as babies get sicker (due to increased mortality risk).

What this means in practice: Centers need to individualize their treatment thresholds based on:

• Local risk profiles

• Family priorities and values

• The specific clinical scenario

Neonatal BPD Outcome Estimator

Steroids for Prevention of BPD: What Does the Research Say?

Hydrocortisone:

What is it: Hydrocortisone is a corticosteroid that has both glucocorticoid AND mineralocorticoid activity. It is a steroid more similar to endogenous cortisol which makes it potentially safer than dexamethasone.

The PREMILOC Protocol (for early use): Consider if your unit's BPD rate is high (≥50th or 75th percentile)

• Especially for infants <1000g exposed to chorioamnionitis

• Started within 24 hours of birth

• 1 mg/kg/day divided twice daily for 7 days

• 0.5 mg/kg/day once daily for 3 days

• Important: Cannot use with NSAIDs due to risk of perforation

• Results: The rate of survival without bronchopulmonary dysplasia at 36 weeks of postmenstrual age was significantly increased by prophylactic low-dose hydrocortisone.

The STOP-BPD Protocol (for later use):

• Started between 7-14 days of life, continuing for 22 days

• Much higher doses than PREMILOC

• 5 mg/kg/day for 7 days, then taper

• Results: Administration of hydrocortisone between 7 and 14 days after birth, compared with placebo, did not improve the composite outcome of death or BPD at 36 weeks’ postmenstrual age. However, there was a significant reduction in mortality by 36 weeks in the Hydrocortisone group.

Dexamethasone:

What it is: This is your most potent anti-inflammatory steroid, about 25 times stronger than hydrocortisone. Dexamethasone: A Randomized Controlled Trial (DART) examined using a short course (10 days) of low dose dexamethasone in infants at high risk (<28 weeks or <1000g who remained on mechanical ventilation after 7 days of life).

The DART Protocol:

• Total dose: 0.89 mg/kg over 10 days

• Day 1-3: 0.15 mg/kg/day divided twice daily

• Day 4-6: 0.10 mg/kg/day divided twice daily

• Day 7-8: 0.05 mg/kg/day divided twice daily

• Day 9-10: 0.02 mg/kg/day divided twice daily

• Results: This RCT showed low-dose dexamethasone treatment after the first 1 week of life facilitates extubation and shortens the duration of intubation among ventilator-dependent, very preterm/extremely low birth weight infants, without any obvious short-term complications. Of note, 85% of infants exposed to dexamethasone had BPD at 36 weeks (compared to 91% of placebo group). A modest reduction that is not statistically significant, though it is important to note the trial was stopped early due to low recruitment.

Key point: In practice, this protocol is typically started after 21 days of life when babies can't wean from the ventilator.

Prednisolone: For Established BPD

Prednisolone is typically reserved for babies who already have established BPD (after 36 weeks PMA) and are still requiring significant respiratory support.

Bhandari Protocol (shorter course):

• 2 mg/kg/day divided twice daily for 5 days

• 1 mg/kg/day once daily for 3 days

• 1 mg/kg/day every other day for 3 doses

• Results: This observational study showed that oral prednisolone therapy is effective in weaning off supplemental oxygen in a postterm infant with oxygen-dependent bronchopulmonary dysplasia who has a pulmonary acuity score of < 0.5 and PCO2 of < 48.5 mmHg. In addition, if a single course of prednisolone fails, there is no clear benefit of using multiple courses.

Timing Is Everything: Early vs. Late Steroid Use

Early Use (< 7 days): BPD Prophylaxis

Here's what the research tells us:

• Hydrocortisone: The PREMILOC protocol showed early low dose hydrocortisone showed a reduction in death and BPD, with no significant difference in the rate of cerebral palsy or neurodevelopmental impairment. Interestingly, the infants treated with hydrocortisone had significantly lower incidence of major cognitive impairment.

• Dexamethasone: Should not be given in the first 7 days of life. The risks outweigh the benefits. 

Late Use (> 7 days): Early Evolving BPD

• Hydrocortisone: Might be preferred if given between 7 and 21 days of life since hydrocortisone may be safer for the brain.

• Dexamethasone: DART protocol showed no increased risk for cerebral palsy or major disability (though there was a small sample size)

• There is a gap in the research to compare hydrocortisone to dexamethasone at this point.

Clinical Tip: Many units use 21 days as their decision point. Before 21 days? Consider hydrocortisone. After 21 days? Dexamethasone becomes a reasonable option.

Nursing Assessment and Monitoring

What should you be monitoring for in your patient receiving steroids?

Glucose Issues:

• Check blood sugars based on your NICU protocol 

• Be ready for insulin if glucose >180-200 mg/dL

• Dexamethasone is notorious for causing hyperglycemia

Blood Pressure:

• Monitor frequently (e.g. every 4-6 hours)

• Steroids make the heart more sensitive to natural stress hormones

GI Complications:

• Watch for feeding intolerance, increased emesis

• Early hydrocortisone + indomethacin = HIGH risk for bowel perforation

  • Steroids and NSAIDs cannot be given together

• Any signs of abdominal distension or bloody stools? Notify the medical team immediately.

Growth and Nutrition:

• Close monitoring of growth and length is crucial

  • Does your unit use a length board?

• Growth deceleration during treatment may occur

  • Recall that steroids may stunt growth

• Work with your dietitians to maximize nutrition

Infection Vigilance

Remember: steroids suppress the immune system. 

• Infants exposed to postnatal corticosteroids have an increased risk of late onset sepsis (I would know this for the RNC-NIC or CCRN-N exam)

• Be extra vigilant with hand hygiene and sterile technique

• Watch for subtle signs of infection (they may not mount a typical response)

• Temperature instability might be your first clue

Adrenal Suppression

When babies receive steroids for more than 14 days, their bodies can "forget" how to make their own stress hormones, like cortisol.

What Is Adrenal Suppression?

Infants are at risk for secondary adrenal insufficiency if they have been given supraphysiologic glucocorticoid doses for more than 14 days. Exogenous supraphysiologic glucocorticoids cause secondary adrenal insufficiency through effects on the hypothalamic-pituitary-adrenal (HPA) axis, the physiologic regulator of endogenous glucocorticoid production.

Signs to Watch For:

• Hypoglycemia 

• Low blood pressure that doesn't respond well to fluids

• Hyponatremia 

• Lethargy, poor feeding

• Fluid retention

The Weaning Process

For babies on steroids ≥14 days, we can't just stop the steroids. Instead the steroids must be gradually tapered. Steroid tapers should be individualized to each patient and may range from a few days to several weeks or months, depending on the duration of steroid therapy

ACTH Stimulation Testing

What is an ACTH Stim Test?

• Normally, adrenocorticotropic hormone (ACTH) is released from the anterior pituitary gland and travels to the adrenal cortex which causes the release of cortisol.

• In an ACTH Stim test, a cortisol level is drawn shortly after administration of exogenous ACTH.

• This allows us to assess the infants response to pituitary hormones.

When do we do this?

• Babies who've been on steroids >14 days to assess adrenal response to ACTH.

• Before stopping maintenance hydrocortisone

• If we're worried about adrenal insufficiency

How it works:

• Give 1 mcg of synthetic ACTH (cosyntropin) IV

• Check cortisol levels at 0, 30, and 60 minutes (it is very important these are drawn at the exact time)

• Normal response: Peak cortisol >18 mcg/dL means the adrenal glands are functioning normally.

RNC-NIC Pearl: Don't rely on random morning cortisol levels in babies—they don't have established circadian rhythms yet.

Family Education: What Parents Need to Know

Help families understand that:

• BPD is a common complication of prematurity affecting lung development

• Corticosteroids are powerful anti-inflammatory medications that may help reduce lung inflammation

• The decision to use steroids involves careful weighing of benefits against potential risks

• The goal is to help their baby wean from the ventilator and reduce long-term breathing problems

Setting Realistic Expectations

Discuss with families:

• Timeline: Effects may not be immediate; improvement typically occurs over days to weeks

• Monitoring: Their baby will need close monitoring for side effects

• Uncertainty: Not all babies respond to steroid therapy

• Long-term outlook: Some babies may still require oxygen or breathing support despite treatment

If Baby Goes Home on Steroids

Some babies might go home on maintenance hydrocortisone. It's important that families know how to give the maintenance medication and how important it is that babies do not miss a dose. In addition, it is important they understand:

Stress Dosing:

• When baby is sick with fever, vomiting, or needs surgery, they need EXTRA steroid because their adrenal glands aren’t able to produce it on its own.

• Hydrocortisone tablets can be crushed and mixed with a small amount of formula

• Parents should be instructed on how to give IM injections in case the infant is unable to take the oral dose. 

Red Flags: Teach families to call immediately for:

• Persistent vomiting (can't keep oral meds down)

• Severe lethargy

• Any fever >101°F

• Before any surgical procedures

As NICU nurses, we're often the first to notice subtle changes that might indicate steroid side effects OR signs that a baby is ready to wean respiratory support. Here are some things I want you to think about:

Questions to ask yourself:

• How comfortable am I explaining to families why we're starting steroids?

• Do I know the signs of adrenal insufficiency?

• When should I be concerned about blood sugar levels in babies on steroids?

• What does my unit's protocol look like for steroid weaning?

For your RNC-NIC preparation:

• Know the different steroids that may be used to prevent BPD. What are the risks and benefits of each?

• Understand the concept of adrenal suppression and how we monitor for it

• Be familiar with side effects and nursing interventions

• Remember that timing of steroid administration affects both efficacy and safety

In Summary

Steroids can be incredibly helpful tools in managing BPD, but they're not magic bullets. Every decision to start steroids involves weighing potential benefits against real risks. As the nurse caring for these babies, you play a crucial role in:

✅ Monitoring for both therapeutic effects and side effects
✅ Educating families about what to expect
✅ Recognizing early signs of complications
✅ Advocating for appropriate weaning and follow-up plans

Remember: you're not just giving medications, you're helping to optimize outcomes for some of our most vulnerable patients while keeping them safe throughout the process.

Want to dive deeper into BPD management? This is exactly the kind of complex topic we cover extensively in my RNC-NIC course. Understanding the nuances of steroid therapy, being able to explain the rationale to families, and knowing how to monitor for complications, these are the skills that set certified NICU nurses apart.

What questions do you have about steroid management in your NICU? I'd love to hear from you!

If you enjoyed this newsletter, I hope you'll share it with a friend! Let's learn together 🤓

Until next time,
Amanda 💛
Your NICU CNS + Study Buddy

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Tala Talks: Preventing BPD

References:

• Cummings JJ, Pramanik AK; COMMITTEE ON FETUS AND NEWBORN. Postnatal Corticosteroids to Prevent or Treat Chronic Lung Disease Following Preterm Birth. Pediatrics. 2022;149(6):e2022057530. doi:10.1542/peds.2022-057530

• Watterberg KL, Walsh MC, Li L, et al. Hydrocortisone to Improve Survival without Bronchopulmonary Dysplasia. N Engl J Med. 2022;386(12):1121-1131. doi:10.1056/NEJMoa2114897

• Baud O, Maury L, Lebail F, et al. Effect of early low-dose hydrocortisone on survival without bronchopulmonary dysplasia in extremely preterm infants (PREMILOC): a double-blind, placebo-controlled, multicentre, randomised trial. Lancet. 2016;387(10030):1827-1836. doi:10.1016/S0140-6736(16)00202-6

• Onland W, Cools F, Kroon A, et al. Effect of Hydrocortisone Therapy Initiated 7 to 14 Days After Birth on Mortality or Bronchopulmonary Dysplasia Among Very Preterm Infants Receiving Mechanical Ventilation: A Randomized Clinical Trial. JAMA. 2019;321(4):354-363. doi:10.1001/jama.2018.21443

• Doyle LW, Davis PG, Morley CJ, McPhee A, Carlin JB; DART Study Investigators. Low-dose dexamethasone facilitates extubation among chronically ventilator-dependent infants: a multicenter, international, randomized, controlled trial. Pediatrics. 2006;117(1):75-83. doi:10.1542/peds.2004-2843

• Bhandari A, Schramm CM, Kimble C, Pappagallo M, Hussain N. Effect of a short course of prednisolone in infants with oxygen-dependent bronchopulmonary dysplasia. Pediatrics. 2008;121(2):e344-e349. doi:10.1542/peds.2006-3668

• McNerney KP, Arbeláez AM. Steroid Use in the NICU: Treatment and Tapering. Neoreviews. 2023;24(4):e207-e216. doi:10.1542/neo.24-4-e207

• Liguori, M., Croop, S., & Trembath, A. Bronchopulmonary Dysplasia.  Fetal and Neonatal Pharmacology for the Advanced Practice Nurse. Springer Publishing Company; 2023.

• Rostas SE, McPherson C. Systemic Corticosteroids for the Prevention of Bronchopulmonary Dysplasia: Picking the Right Drug for the Right Baby. Neonatal Netw. 2016;35(4):234-239. doi:10.1891/0730-0832.35.4.234

• Doyle LW, Cheong JL, Ehrenkranz RA, Halliday HL. Early (< 8 days) systemic postnatal corticosteroids for prevention of bronchopulmonary dysplasia in preterm infants. Cochrane Database Syst Rev. 2017;10(10):CD001146. Published 2017 Oct 24. doi:10.1002/14651858.CD001146.pub5

• Yu H, Li D, Zhao X, Fu J. Fetal origin of bronchopulmonary dysplasia: contribution of intrauterine inflammation. Mol Med. 2024;30(1):135. Published 2024 Sep 3. doi:10.1186/s10020-024-00909-5

• Greenberg RG, McDonald SA, Laughon MM, et al. Online clinical tool to estimate risk of bronchopulmonary dysplasia in extremely preterm infants. Arch Dis Child Fetal Neonatal Ed. Published online June 21, 2022. doi:10.1136/archdischild-2021-323573

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