🧠 Neonatal Delirium: A Guide for NICU Nurses

Delirium in neonates represents one of the most under-recognized complications in our NICUs—yet its presence is linked to longer hospital stays, disrupted neurodevelopment, and increased mortality in older children. With prevalence rates estimated at 22% in term-equivalent age infants, this acute brain dysfunction deserves our immediate attention and understanding.

Pathophysiology: The Developing Brain Under Stress

Delirium is best understood as acute brain dysfunction resulting from multiple intersecting mechanisms:

• Neurotransmitter imbalance: The neonatal brain is uniquely vulnerable due to GABA receptors being excitatory(rather than inhibitory as in adults), making benzodiazepines particularly problematic

  • Benzodiazepines (like midazolam, lorazepam, diazepam)enhance GABA-A receptor activity.

  • In an immature brain → this enhances excitation→ paradoxical agitation, abnormal tone, and potential neurotoxicity.

• Neuroinflammation: Systemic illness triggers inflammatory cascades affecting brain function

• Oxidative stress: Compromises cellular function and neurotransmission

• Circadian disruption: Affects melatonin production and sleep-wake cycles

• Neuronal disconnectivity: Disrupts normal brain network communication

These overlapping pathways all culminate in impaired attention, sleep disruption, and fluctuating alertness—the hallmark signs nurses may observe at the bedside.

Risk Factors: Recognizing Our Most Vulnerable Patients

There are many risk factors we as nurses must be aware of when it comes to delirium. Some of these risks factors are things we cannot change and have no control over. But what can we change? Let's review the risk factors together.

Non-modifiable risks:

• Age <2 years (especially neonates)

  • The immature brain has a developing blood–brain barrier, high plasticity, and heightened sensitivity to stress and neurotransmitter imbalance.

• Developmental delays

  • Baseline cognitive or behavioral differences make delirium harder to detect and may amplify risk.

• Neurologic conditions (HIE, IVH grade 3-4, congenital malformations)

  • Structural or metabolic brain injury increases susceptibility to neurotransmitter disruption and impaired arousal regulation.

• Cyanotic heart disease

  • Chronic hypoxemia alters cerebral perfusion and oxygen delivery, affecting neuronal stability.

Modifiable pharmacologic risks we can influence:

• Benzodiazepine exposure (4-fold increased risk and dose-dependent)

  • Potentiate GABA-A activity: paradoxically excitatory in neonates → disorganized behavior, sleep disruption.

• Anticholinergic medications

  • Block acetylcholine, a key neurotransmitter for attention and arousal.

• Opioids

  • Chronic use leads to receptor downregulation, tolerance, and withdrawal cycles → fluctuating arousal, mimicking delirium.

• Corticosteroids

  • Alter glucose metabolism and can induce mood or behavioral changes.

• Rapid weaning

  • Sudden changes in CNS drug exposure can trigger agitation, autonomic instability, and delirium.

Delirium risk rises exponentially when multiple deliriogenic medications are combined. Polypharmacy is a major modifiable factor.

Environmental Considerations: an area nurses can greatly influence

• Sleep deprivation

  • Loss of circadian rhythm and melatonin suppression impairs neuronal repair and increases cortisol.

• Excessive light/noise exposure

  • Sensory overload causes overstimulation of the reticular activating system.

• Frequent handling and procedures

  • Repeated stress responses (↑catecholamines & cortisol) interfere with attention and sleep–wake cycles.

• Immobility or restraints

  • Loss of proprioceptive input and comfort increases disorientation and agitation.

• Isolation from caregivers

  • Lack of familiar voices and touch worsens disorganization and distress.

• Pain

  • Uncontrolled pain activates the HPA axis, perpetuating neuroinflammation.

This is why consistent caregivers, clustered care, and parental presence are all delirium-prevention interventions—not just comfort measures.

Clinical Presentation: What to Watch For

Hyperactive delirium(most reported but least common):

• Refractory agitation unresponsive to escalating sedatives

• Inability to console for prolonged periods

• Severe sleep disturbance

• Disorganized behaviors

While I have been learning about delirium one of my first thoughts was, "how do I as a nurse distinguish hyperactive delirium from something like "air hunger" (in our BPD kiddos) or withdrawal?

Hyperactive delirium, by definition is: A fluctuating state of excessive arousal and disorganization—the baby is overstimulated, inconsolable, and dysregulatedin a way that doesn’t fit their clinical picture or respond to usual soothing or pharmacologic measures.

When a baby is agitated, our instinct is often to treat the "noise"(increase sedation, give a dose of morphine, adjust ventilator).
But taking a moment to pause and evaluate is where expert nurses shine.

Other than agitation what is the baby showing us that may tell us more about their issue?

• In air hunger, there is physiologic distress due to hypoxia, hypercarbia, and increased WOB

  • ↑ RR and retractions, tachycardia, desaturation, grimacingonly when breathing effort increases, calms with improved ventilation or repositioning

• Withdrawal is signs of physiologic distress due to a tolerance after prolonged exposure to medication like opioids

  • High-pitched cry, sweating, sneezing, yawning, loose stools, tremors, fever, mottling, feeds poorly; WAT-1 > 3; symptoms are predictable, rhythmic

• Delirium occurs when there is disorganized brain signals

  • Inconsolable even when physiologic needs met, fluctuating arousal (hyper-alert → drowsy → panicked), stares through caregivers, disturbed sleep–wake cycle, waxing/waning course

Withdrawal and delirium can overlap. If a baby is consistently inconsolable but still has moments of calm, withdrawal is likely. If agitation fluctuates without clear pattern: consider delirium.

Use objective scales as guides:

• WAT-1 for withdrawal

• CAPD for delirium

• RASS, SBS, or NPASS for sedation level

If WAT-1 is low but CAPD is elevated (≥9): that’s a red flag there may be delirium rather than withdrawal.

Also look for fluctuation over time: delirium waxes and wanes. Withdrawal does not.

What about Hypoactive delirium?

Hypoactive delirium is the most common, the most under-recognized, and potentially the most dangerous form of delirium in critically ill neonates. It’s quiet, subtle, and easy to misinterpret as “comfortable” — when in reality, the baby may be experiencing acute cerebral dysfunction.

• Decreased arousal and somnolence

  • Alternates between appearing asleep and wide-eyed but disengaged

• Apathy and withdrawal

  • Doesn’t resist cares, no purposeful suck or grasp

• Reduced response to stimulation

  • No longer tracks faces, doesn’t orient to sound or light

• Flat or absent affect

  • No spontaneous facial expressions; less crying or cooing

• Reduced spontaneous movements

  • Limbs stay flexed or extended, minimal stretch/yawn/startle

• Often mistaken for appropriate sedation

🧠 Pathophysiology

In the developing brain, delirium reflects network dysfunction— specifically, disruption of the ascending reticular activating system, which regulates attention, sleep–wake cycling, and arousal.

Factors like inflammation, sedative exposure (especially benzos and opioids), and disrupted circadian rhythm dampen this system.
When this happens, the infant loses the ability torespond appropriately to stimuli.

⚠️ When “Calm” Becomes Concerning

We should pause when:

• The infant stops responding to familiar voices or gentle stimulation.

• A previously interactive baby suddenly becomes withdrawn or lethargic.

• There is no physiologic explanation (no infection, new meds, or sedation increase).

• CAPD scores begin creeping upward even though the baby appears “quiet.”

• The infant loses developmental behaviors(tracking, sucking, consolability.)

👩🏻‍⚕️ Nursing Interventions

If hypoactive delirium is suspected:

1. Assess & communicate

   • Share behavioral concerns with the team and document CAPD score trends.

   • Ask: “Could this be delirium rather than oversedation?”

2. Re-evaluate medications

   • Review benzodiazepine, opioid, and steroid exposure.

   • Collaborate with the team to minimize deliriogenic drugs.

3. Re-engage the brain

   • Dim lights at night, brighten during day (restore circadian cues).

   • Encourage parent voice, touch, and kangaroo care.

   • Provide gentle, age-appropriate stimulation (soft music, containment).

4. Normalize sleep

   • Protect longer, uninterrupted rest periods.

   • Cluster cares and avoid unnecessary overnight interventions.

⚖️Mixed Delirium

🧠 What It Is

Mixed delirium means the infant fluctuates between hyperactive and hypoactive states... sometimes within hours, sometimes across shifts.
You might see a baby who is inconsolable and thrashing one moment… and then listless and disengaged the next.

That unpredictability is your clue.

👀 Clinical Presentation

• Alternating periods of agitation and withdrawal

• One shift: “She’s so fussy, I can’t calm her.”
  Next shift: “She’s been sleeping all day and barely moves.”

• Variable responsiveness to voice, touch, or containment

• Disturbed sleep–wake cycle— wide awake overnight, drowsy during the day

• Episodes of tachycardia or desaturation without clear triggers

📍Unlike withdrawal (predictable, sustained hyperarousal), mixed delirium waxes and wanes unpredictably.

💡 Nursing Takeaways

1. Document the pattern, not just the moment.
   – Delirium reveals itself over time. A single observation can miss it.
   – Use validated tools to score activities throughout your shift (not just a moment in time)

2. Communicate between shifts.
   – Mixed delirium often only becomes obvious when nurses compare notes:

   “He was wild all night but slept through cares this morning.”

3. Score consistently.
   – CAPD (Cornell Assessment of Pediatric Delirium) is especially valuable because it reflects behavior over a shift, not a point-in-time snapshot.

4. Investigate the change in behavior
   – Sudden change from calm → chaotic often points to an environmental or medication trigger (new sedative, change in ventilation, infection, overstimulation).

Nursing Interventions: Your Critical Role

Non-Pharmacological Strategies (First-Line)

Environmental Optimization:

• Implement quiet hours (e.g. 2300-0500)

• Maintain day/night cycling with appropriate lighting

• Cluster cares to protect sleep periods

• Reduce unnecessary alarms and noise

Developmental Support:

• Encourage family presence and involvement

• Provide age-appropriate sensory experiences

• Support early mobility when possible

• Maintain consistent caregivers when feasible

Sleep Protection:

• Reschedule non-urgent procedures/labs outside sleep hours

• Use cycled lighting

• Minimize sleep interruptions

Medication Considerations

Gabapentin:

• Often used for refractory agitation or pain

• Typical dosing: 5 mg/kg/dose every 8-12 hours

• Associated with decreased opioid requirements

• Monitor for:

  • Sedation

  • Feeding tolerance

• No adverse events noted in recent studies

Melatonin:

• Primary indication: sleep promotion (52.7% of cases)

• Typical dose: 0.31 mg/kg/dose

• Usually given once a day in the evening

• May reduce opioid exposure

• Well-tolerated with no reported adverse events

A recent NICU delirium protocol recommends starting with gabapentin for pain-related agitation or melatonin for sleep disruption before considering antipsychotics.

🔬Screening Tools: The CAPD

CAPD (Cornell Assessment of Pediatric Delirium):

TheCAPD is an 8-item observational tool designed to detect delirium in infants and children based on behavior over an entire nursing shift —not a snapshot in time.

Each of the 8 items assesses domains like:

• Attention and awareness

• Interaction

• Consciousness level

• Motor activity

• Sleep–wake cycle

• Response to comfort

• Fluctuations over time

Because a 2-month-old behaves very differently from a 2-year-old, the anchor points guide the nurse in determining what “normal” looks like for that developmental stage. See photo below (I know its super tiny and hard to read so I also linked the citation below).

Silver, Kearney, Traube, & Hertzig, 2015

Each of the 8 items is scored 0–4 (normal → severely abnormal).

• 0–8:Normal

• 9–12:Possible delirium

• ≥13:Probable delirium

ACAPD ≥9 should prompt the nurse or team to evaluate for delirium and consider possible underlying causes.

Key Nursing Actions:

1. Screen routinely using CAPD (once per shift): Delirium fluctuates throughout the day; routine screening each shift helps capture these changes and measure progress.

2. Document behavioral changes and responses to interventions

3. Advocate for minimizing deliriogenic medications

4. Collaborate with team on sedation weaning strategies

5. Support family engagement and education

Red Flags Requiring Immediate Action

• Sudden behavioral regression

• Inability to maintain eye contact or attend to faces

• Complete failure to respond to comfort measures

• Extreme agitation requiring escalating sedatives without improvement

If something feels ‘off’ about a baby’s behavior or responsiveness—trust your clinical instincts and speak up.

Check out this great video from Dr. Tala on Youtube! She an Jen Miller, NNP have a great discussion about neonatal delirium so you can learn more about it.

Click here

Early recognition and prevention are key. Delirium is not just agitation—it’s acute brain dysfunction. Every calm environment, every protected sleep cycle, every family interaction matters.

While we await more NICU-specific research, implementing these evidence-based strategies can help protect our most vulnerable patients' developing brains.

Get this CUTE NICU Nurse Era t-shirt from my friends at Nicuity

Does your team have a Delirium guideline, protocol, or pathway? What's one thing you can do to help your team start looking at delirium? If you're team is already doing a great job, what are you doing?

Email me and let me know!

Stay Curious,

Amanda

© 2025 This content is for educational purposes and should complement, not replace, your unit's policies and procedures.

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References:

Bradford, C., Miller, J. L., Harkin, M., Chaaban, H., Neely, S. B., & Johnson, P. N. (2023).Melatonin use in infants admitted to intensive care units.Journal of Pediatric Pharmacology and Therapeutics, 28(7), 635–642.https://doi.org/10.5863/1551-6776-28.7.635

Chang, E., Parman, A., Johnson, P. N., Stephens, K., Neely, S., Dasari, N., Kassa, N., & Miller, J. L. (2024).Gabapentin for delirium in infants in the neonatal intensive care unit.Journal of Pediatric Pharmacology and Therapeutics, 29(5), 487–493.https://doi.org/10.5863/1551-6776-29.5.487

Ruth, O., Tomajko, S., Dabaja, E., Munsel, E., Rice, K., Cwynar, C., Maye, M., & Malas, N. (2024).Current evidence regarding the evaluation and management of neonatal delirium.Current Psychiatry Reports, 26(10), 744–752.https://doi.org/10.1007/s11920-024-01550-z

Ruth, O., & Malas, N. (2024).Neonatal delirium.Seminars in Fetal and Neonatal Medicine, 29, 101567.https://doi.org/10.1016/j.siny.2024.101567

Silver, G., Kearney, J., Traube, C., & Hertzig, M. (2015). Delirium screening anchored in child development: The Cornell Assessment for Pediatric Delirium.Palliative & supportive care,13(4), 1005–1011.https://doi.org/10.1017/S1478951514000947