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Case 017: Hemodynamically Significant PDA in Preterm Infant

Clinical Presentation

Setting: Neonatal Intensive Care Unit

Patient: 26-week gestational age male, now day of life 5

History: - Born at 26+0 weeks via emergent C-section for preeclampsia - Birth weight 780g (AGA) - Received antenatal steroids (2 doses) - Intubated at delivery, surfactant x2 - Currently on HFOV with FiO2 60%

Problem: Respiratory status not improving as expected. Cardiology consulted for evaluation of murmur noted today.

Relevant NICU Course: - Day 1-2: Improving on conventional vent, FiO2 30% - Day 3: Required transition to HFOV, FiO2 increasing - Day 4-5: Continued escalation, now FiO2 60% - Unable to tolerate feeds

Initial Assessment

Vital Signs: - HR 168 - RR (on HFOV) - MAP (mean airway pressure) 14 - SpO2 91% on FiO2 60% - BP 42/18 (MAP 26) - widened pulse pressure

Physical Exam: - General: Small, intubated preterm infant - Cardiac: Hyperdynamic precordium, continuous "machinery" murmur at LUSB, bounding peripheral pulses - Lungs: Diffuse crackles, poor air entry - Abdomen: Soft, full, not tolerating feeds - Extremities: Widened pulse pressure appreciated

Diagnostic Workup

Echocardiogram Findings

PDA Assessment: - PDA present: 3.2mm diameter (large for size) - Flow: Left to right, continuous - LA:Ao ratio: 2.0 (dilated LA) - LV diastolic dimension: Dilated (Z-score +2.5) - LV function: Hyperdynamic (EF 75%) - Descending aortic flow: Reversal of diastolic flow ("ductal steal") - Mitral E velocity: Increased - LVOT VTI: 25 cm (increased)

Qualitative Assessment: Large, hemodynamically significant PDA with volume overload

Clinical Reasoning Questions

Question 1

What echocardiographic features indicate this PDA is hemodynamically significant (hsPDA)?

Answer **Markers of Hemodynamically Significant PDA:** **This Patient's Echo Findings:** | Finding | This Patient | Threshold for hsPDA | |---------|--------------|---------------------| | **PDA diameter** | 3.2mm | >1.5mm or >1.5mm/kg | | **LA:Ao ratio** | 2.0 | >1.5 (indicates LA volume overload) | | **LV dilation** | Z-score +2.5 | Present = volume overload | | **Diastolic flow reversal** | Present | Any reversal = steal phenomenon | | **LV function** | Hyperdynamic (75%) | Hyperdynamic = volume overloaded | **What Each Finding Means:** 1. **PDA Size**: Larger PDA = more shunt volume 2. **LA:Ao Ratio**: Left atrium dilated from increased pulmonary venous return (all the blood shunted to lungs comes back) 3. **LV Dilation**: Volume overload from handling pulmonary + systemic output 4. **Diastolic Flow Reversal**: Blood flows retrograde in descending aorta during diastole ā†’ "steals" from mesenteric, renal, cerebral circulations 5. **Hyperdynamic LV**: Heart pumping more volume to compensate **Absent/Reverse End-Diastolic Flow in:** - Descending aorta - Celiac/mesenteric arteries - Renal arteries - Middle cerebral artery (concerning)

Question 2

What are the clinical consequences of a large PDA in this preterm infant?

Answer **Consequences of hsPDA:** **Pulmonary Effects (Volume Overload):** - Increased pulmonary blood flow - Pulmonary edema - Worsening respiratory status - Prolonged ventilator dependence - May contribute to BPD development **Systemic Effects (Ductal Steal):** | Organ | Consequence | |-------|-------------| | **Gut** | NEC risk from mesenteric hypoperfusion | | **Kidney** | Oliguria, AKI from renal hypoperfusion | | **Brain** | IVH risk (though controversial), abnormal cerebral autoregulation | **Heart Effects:** - LV volume overload - Eventually can lead to heart failure - Tachycardia, hepatomegaly (late signs) **This Patient:** - Worsening respiratory status (pulmonary overcirculation) - Unable to tolerate feeds (mesenteric steal concern) - Widened pulse pressure (aortic runoff) - Hyperdynamic precordium **Key Concept:** The PDA creates a "vascular short circuit" - blood that should go to the body instead goes back to the lungs, causing pulmonary congestion AND systemic hypoperfusion simultaneously.

Question 3

What are the current treatment options for hsPDA and how do you choose?

Answer **Treatment Options:** **1. Conservative/Expectant Management** - Fluid restriction - Permissive hypercapnia - Diuretics (controversial) - Wait for spontaneous closure **2. Pharmacologic Closure** | Drug | Mechanism | Dosing | Success Rate | |------|-----------|--------|--------------| | **Ibuprofen** | COX inhibition | 10-5-5 mg/kg q24h x 3 doses | 70-80% | | **Indomethacin** | COX inhibition | 0.2-0.1-0.1 mg/kg q12-24h | 70-80% | | **Acetaminophen** | COX inhibition (peroxidase) | 15 mg/kg q6h x 3-7 days | 70-80% (variable) | **3. Surgical Ligation** - Via thoracotomy, clip or ligate PDA - Reserved for: Medical failure, contraindications, large PDA **4. Transcatheter Closure** - Emerging option even in small preterms - Limited availability, size constraints - Experienced centers only **Decision Making:** This patient = good candidate for **pharmacologic treatment**: - Large hsPDA with clinical consequences - No contraindications (no IVH, no NEC, no renal failure, no thrombocytopenia) - Day of life 5 = still within window for medical therapy **Contraindications to NSAIDs:** - Recent or active IVH - NEC or intestinal pathology - Renal failure (Cr >1.8) - Thrombocytopenia (<50,000) - Active bleeding

Question 4

The PDA-TOLERATE trial changed practice. What were its key findings?

Answer **PDA-TOLERATE Trial (2019):** **Design:** - Multicenter RCT - Preterm infants <28 weeks with moderate-large PDA - Randomized to early treatment vs. conservative management **Key Findings:** | Outcome | Early Treatment | Conservative | P-value | |---------|-----------------|--------------|---------| | **Primary composite** (death/BPD/other) | No difference | No difference | NS | | **BPD** | No difference | No difference | NS | | **NEC** | No difference | No difference | NS | | **PDA ligation rate** | Lower | Higher | Significant | **Implications:** 1. **Many PDAs close spontaneously** without treatment 2. **Routine early treatment** doesn't improve major outcomes 3. **Conservative approach is reasonable** for many 4. **But doesn't mean NEVER treat** - selective treatment still appropriate **Who Still May Benefit from Treatment?** - Very large, hemodynamically significant PDA - Failing despite supportive care - Unable to wean respiratory support - Clinical deterioration attributable to PDA **Current Practice Shift:** - Less automatic treatment of all PDAs - More "targeted" approach based on hemodynamic significance - Longer trial of conservative management - Treatment reserved for symptomatic hsPDA

Question 5

You decide to treat with ibuprofen. How do you monitor response?

Answer **Monitoring During/After Treatment:** **Clinical Monitoring:** - Respiratory status (FiO2, MAP requirements) - Urine output (risk of oliguria with NSAIDs) - Feeding tolerance - Murmur characteristics - Pulse pressure **Laboratory Monitoring:** - Creatinine (before each dose, hold if rising) - Platelet count - Bilirubin (ibuprofen displaces from albumin) **Echocardiographic Follow-up:** - After completing course (24-48h after last dose) - Assess: PDA size, flow pattern, LA:Ao ratio, diastolic reversal **Expected Response:** | Finding | Successful Closure | Persistent/Residual | |---------|-------------------|---------------------| | PDA flow | None | Persistent Lā†’R | | LA:Ao | Normalizing (<1.4) | Still elevated | | Diastolic reversal | Resolved | Persistent | | Respiratory | Improving | No improvement | **If First Course Fails:** Options: 1. Second course of ibuprofen (lower success rate) 2. Switch to different NSAID 3. Acetaminophen course 4. Surgical ligation 5. Catheter closure (if available) **Rescue Ligation Criteria:** - Failed 2 courses of medical therapy - Contraindication to medical therapy - Hemodynamic instability - Ongoing clinical deterioration

Question 6

What are the long-term considerations for this patient?

Answer **If PDA Closes:** - Excellent prognosis from cardiac standpoint - No long-term cardiac follow-up needed for closed PDA - Prematurity-related issues (BPD, ROP, developmental) remain **If PDA Persists (Discharged with PDA):** - Most small residual PDAs close by 1-2 years - Follow-up echo to monitor - May need intervention if persistent + symptomatic **Indications for Late Intervention:** - Persistent moderate-large PDA - Volume overload on echo - Failure to thrive - Recurrent respiratory infections **Intervention Options:** - Device closure (standard for >6kg, some do smaller) - Surgical ligation **Neurodevelopmental Outcomes:** - hsPDA associated with worse neurodevelopmental outcomes - Surgical ligation also associated with adverse outcomes - Unclear if treatment improves or worsens this - The PDA may be a marker of illness severity, not the cause **Key Point:** The long-term morbidities of extreme prematurity (BPD, developmental delay) are more significant than the PDA itself for most infants.

Hospital Course

The infant received a 3-dose course of IV ibuprofen starting on DOL 5. He tolerated treatment without significant renal dysfunction. Repeat echo on DOL 8 showed: - PDA: Small (1.2mm), restrictive flow - LA:Ao: 1.3 (normalized) - No diastolic flow reversal

Respiratory status improved, weaned to conventional ventilation by DOL 10. Follow-up echo at 2 weeks showed complete PDA closure. He was discharged home at 40 weeks corrected GA with resolving BPD.

Key Teaching Points

  1. Hemodynamically significant PDA = large PDA with volume overload (LA:Ao >1.5, LV dilation, diastolic flow reversal)
  2. Ductal steal causes systemic hypoperfusion (mesenteric ā†’ NEC risk, renal ā†’ oliguria)
  3. PDA-TOLERATE trial supports conservative management for many PDAs
  4. Treatment is reserved for symptomatic hsPDA with clinical consequences
  5. Ibuprofen, indomethacin, acetaminophen all have similar efficacy
  6. NSAIDs contraindicated with IVH, NEC, renal failure, thrombocytopenia
  7. Most PDAs close spontaneously in preterm infants
  8. Long-term prognosis depends more on prematurity complications than PDA itself

References

  • Hundscheid T, et al. PDA-TOLERATE Trial. N Engl J Med. 2019
  • Benitz WE. Pediatrics. 2016 - PDA Natural History