Anaesthetic Management of a Child with Stickler Syndrome

Background and Relevance to Anaesthesia

Key Systemic Features Relevant to Anaesthesia

Pre-operative Assessment

Airway Assessment

• Mandatory and thorough: assess for micrognathia, mouth opening, Mallampati class, neck mobility, tongue size (glossoptosis), and presence of cleft palate.
• The Pierre Robin triad (micrognathia + glossoptosis + U-shaped cleft palate) is present in a significant proportion - these patients are at highest risk.
• Ultrasound-guided airway assessment has been described as a useful adjunct in cooperative children, as reported in a 2-year-old with Stickler syndrome undergoing cleft palate repair (Veiga et al., Cureus 2023).
• Review any previous anaesthetic records - a prior documented difficult airway is the strongest predictor of future difficulty.
• Children with known difficult airways should wear a medical alert bracelet (recommended by Zimmermann et al.).

Additional Pre-operative Work-up

• Cervical spine X-ray or MRI if atlantoaxial instability is suspected (joint hypermobility).
• Cardiology review is not routinely required but consider if marfanoid features are prominent.
• Baseline oxygen saturation and polysomnography if obstructive sleep apnoea is suspected.
• ENT review if significant sensorineural hearing loss or otitis-related conductive loss.

Intraoperative Anaesthetic Management

Airway Strategy - The Core Challenge

Risk Stratification

• Lower risk: no cleft palate, no receding mandible, older child with prior uneventful GA - standard technique acceptable.
• Higher risk: cleft palate, micrognathia/receding mandible, PRS, history of difficult airway, infant/toddler - experienced operator, full difficult airway equipment ready, awake/semi-awake or inhalational induction.

Induction Technique

• Inhalational induction (sevoflurane in 100% O2) with maintained spontaneous breathing is preferred in anticipated difficult paediatric airways. This allows time to assess airway patency before neuromuscular blockade.
• Avoid muscle relaxants until the airway is confirmed secure unless rescue ventilation is possible.
• An antisialogogue (atropine 20 mcg/kg IM, or glycopyrrolate) pre-operatively reduces secretions and aids visualisation - particularly important for fiberoptic techniques.
• Awake fiberoptic intubation is not routinely feasible in young children but can be considered in cooperative older children or adolescents.

Airway Devices - Equipment Ready

1. Video laryngoscope (e.g., GlideScope, C-MAC) - preferred first choice in known/anticipated difficult airway
2. Flexible fiberoptic bronchoscope - especially useful when micrognathia severely limits line-of-sight laryngoscopy
3. Supraglottic airway devices (LMA/i-gel) - both as primary technique (for short procedures not requiring intubation) and as a conduit for fiberoptic intubation
4. Range of ETT sizes and stylets/bougie
5. Surgical airway capability (needle cricothyrotomy kit, ENT surgeon on standby for complex cases)

Positioning

• Careful head and neck positioning - avoid excessive extension/flexion if cervical instability is suspected.
• Pad all pressure points given joint hypermobility and arthropathy.
• Eye protection is mandatory (myopia, prior retinal procedures, corneal fragility).

Maintenance

• TIVA (propofol + remifentanil) or inhalational (sevoflurane/desflurane) depending on surgical type.
• For ophthalmic surgery (retinal detachment): avoid agents that raise IOP:
  • Avoid suxamethonium (raises IOP by ~5-10 mmHg) in open-eye surgeries.
  • Avoid ketamine as sole agent (may raise IOP and cause movement).
  • Aim for smooth, deep anaesthesia at intubation/extubation - coughing and bucking must be minimised.
  • Nitrous oxide is contraindicated if sulphur hexafluoride (SF6) or perfluoropropane (C3F8) gas tamponade has been used intra-ocularly (can expand the gas bubble and cause catastrophic IOP rise and vision loss). Confirm with surgeon before any retinal procedure.
• For cleft palate repair: RAE tube or reinforced tube; throat pack; vigilance for tube kinking/displacement during palate manipulation; plan for post-operative airway management (these children often have residual upper airway compromise).

Post-operative Management

• Extended post-operative monitoring is warranted in children with PRS or obstructive sleep apnoea features - supplemental oxygen, pulse oximetry, prone/lateral positioning.
• Extubation should be performed awake (not deep) if the airway was difficult to secure - the same difficulties will be encountered should re-intubation be required.
• Have re-intubation equipment immediately available at extubation.
• Minimise opioids post-operatively (respiratory depression risk in PRS/OSA); consider paracetamol + NSAIDs as first-line with careful opioid titration if needed.
• Retinal surgery recovery: avoid face-down positioning conflicts with anaesthetic recovery needs - coordinate with surgeon.
• Avoid sudden IOP-raising events in the post-operative period (straining, coughing, PONV): use prophylactic antiemetics (ondansetron + dexamethasone), smooth extubation technique.

Summary of Key Anaesthetic Principles

1. Pre-operative airway assessment is mandatory - identify PRS features, cleft palate, and micrognathia as the highest-risk predictors of difficult airway.
2. Anticipate and plan for difficulty - have video laryngoscope, fiberoptic scope, SADs, and surgical airway backup ready before induction.
3. Maintain spontaneous ventilation during induction until airway is secured (inhalational induction preferred in high-risk infants/toddlers).
4. Nitrous oxide is contraindicated if intraocular gas tamponade has been placed.
5. Suxamethonium should be avoided in open-globe situations.
6. Awake extubation - never extubate deep if intubation was difficult.
7. Post-operative OSA monitoring in children with PRS.
8. Document and communicate - update anaesthetic records, recommend medical alert bracelet if difficult airway is confirmed.
9. Most Stickler patients (~92-97%) can be managed with a single attempt - standard technique is acceptable in lower-risk children, but a senior, experienced anaesthetist should manage those with mandibular recession or cleft palate history.

Key References

• Zimmermann et al. (2021) - 502-patient case series: the largest published series; confirms receding mandible and cleft palate as significant risk predictors (PMID 31856005)
• Veiga et al. (2023) - Pediatric case report: 2-year-old, cleft palate repair, ultrasound airway assessment (PMID 38161915)
• Kanski's Clinical Ophthalmology 10th ed., Chapter 15 - Stickler syndrome systemic and ocular features
• K.J. Lee's Essential Otolaryngology - Stickler syndrome craniofacial features

Anaesthetic Management: Stickler Syndrome Baby for ASD Closure

• Syndrome-specific: Difficult airway (micrognathia, Pierre Robin sequence, cleft palate)
• Cardiac: ASD physiology, cardiopulmonary bypass (CPB) in an infant, post-bypass haemodynamics

Understanding the Combined Pathology

Stickler Syndrome + ASD: Is the Link Real?

ASD Physiology Review (Anaesthetically Relevant)

• Left-to-right shunt (L→R): elevated pulmonary blood flow, RV volume overload
• Direction and magnitude depend on defect size and relative ventricular compliance
• In infants: increased pulmonary blood flow (Qp:Qs > 1), right atrial and ventricular dilation
• Unrepaired large ASDs risk: pulmonary arterial hypertension (PAH), RV dysfunction, Eisenmenger syndrome (late)
• Paradoxical air embolism risk: any air in IV lines can cross to systemic circulation via the ASD - this is a critical intraoperative concern
• Inhalational agent pharmacokinetics: increased pulmonary blood flow speeds uptake of inhalational agents slightly (wash-in faster), but IV agent effect is minimally diluted by short pulmonary circulation time

Pre-operative Assessment

Airway

• Thorough airway assessment is the top priority: look for micrognathia, mouth opening limitation, Mallampati class, Pierre Robin features (micrognathia + glossoptosis + U-shaped cleft palate), mid-facial hypoplasia
• Review all previous anaesthetic records - any documented difficult intubation mandates full difficult airway preparation
• A receding mandible and/or cleft palate history are the two strongest independent predictors of difficult airway in Stickler syndrome (Zimmermann et al., Anesth Analg 2021, n=502)
• Consider ultrasound airway evaluation as an adjunct in cooperative infants

Cardiac Work-up

Type of Closure: Surgical vs Device?

• ASD closure is generally deferred until after 2 years - so an infant being taken for ASD closure has a specific indication (symptomatic heart failure, large shunt, failure to thrive)
• Device (catheter-based) closure: suitable for secundum ASDs with adequate rims; performed under general anaesthesia with TOE guidance in cardiac catheterisation lab; no CPB required
• Surgical closure (sternotomy or mini-thoracotomy): required for primum ASD, sinus venosus type, large secundum without rims, or in very small infants; requires CPB
• The anaesthetic implications are fundamentally different - establish this preoperatively

Intraoperative Anaesthetic Management

Priority Order at Induction:

Airway FIRST → Cardiac haemodynamics second. A failed airway is immediately life-threatening; ASD haemodynamics are relatively forgiving at induction.

1. Pre-induction Setup

• Two large-bore IV cannulae (meticulously air-bubble free - paradoxical embolism risk via ASD)
• All IV lines must have in-line air filters or be rigorously de-aired
• Arterial line (radial - awake or post-induction depending on child's condition)
• Full monitoring: SpO2, ETCO2, invasive arterial BP, temperature, near-infrared spectroscopy (NIRS) for cerebral and somatic oxygenation (especially during CPB)
• Transesophageal echocardiography (TEE/TOE) - after intubation; used to guide device closure and confirm surgical repair

2. Induction - The Critical Step

Airway Risk Stratification:

• High-risk features (cleft palate, micrognathia/PRS): inhalational induction with sevoflurane in 100% O2, maintain spontaneous ventilation until airway secured
• Lower-risk (no PRS features, prior uncomplicated intubation documented): IV induction acceptable

Inhalational Induction in an ASD Baby:

• Sevoflurane 8% initially for speed, then reduce to 4-5% maintenance
• In L→R shunt, increased pulmonary flow may slightly accelerate inhalational agent washout - but in practice, sevoflurane induction is not meaningfully impaired
• The ASD shunt direction means there is no risk of paradoxical hypoxaemia from R→L shunting at induction in an uncomplicated ASD (unlike cyanotic CHD), so inhalational induction is safe

Full Difficult Airway Kit Ready:

1. Video laryngoscope (DCI/Storz/GlideScope paediatric blade) - first choice
2. Flexible fibreoptic bronchoscope (sized for infant)
3. Supraglottic airway (LMA) as conduit/rescue
4. Multiple ETT sizes with stylet/bougie
5. ENT surgeon/surgical airway standby for complex cases
6. Limit to 2 direct laryngoscopy attempts then switch technique; repeated attempts cause progressive oedema

Intubation:

• Oral RAE tube (suits sternotomy/thoracotomy positioning)
• Confirm with ETCO2 and bilateral chest auscultation
• Secure tube well - repositioning during surgery is not possible on bypass

Neuromuscular Blockade:

• Rocuronium (preferred; non-depolarising) once airway is confirmed secured
• Avoid suxamethonium unless emergency (potential hyperkalaemia risk, not specifically in Stickler but general principle for elective paediatric cardiac cases)

3. Maintenance

Agents:

• High-dose opioid technique is standard for paediatric cardiac surgery: fentanyl (25-50 mcg/kg) or sufentanil for blunting stress response and pulmonary vasospasm - particularly important if there is any pulmonary hypertension
• Volatile agent (isoflurane or sevoflurane) for supplementary anaesthesia
• Benzodiazepine (midazolam) for amnesia
• TIVA (propofol + remifentanil) is an alternative if total TIVA is preferred; avoids any volatile agent interaction
• Ketamine: generally avoided in PAH (raises PVR) - check preoperative PA pressures

Haemodynamic Goals for ASD:

4. Cardiopulmonary Bypass (if surgical repair)

• Heparinisation prior to CPB (300-400 IU/kg; ACT target >480 seconds)
• CPB circuit prime - paediatric circuit with smallest possible priming volume (blood prime in small infants to prevent haemodilution)
• Hypothermia on bypass: moderate (28-32°C) for most ASD repairs; deep hypothermic circulatory arrest only if complex associated lesions
• During CPB:
  • Maintain cerebral NIRS >50% or within 20% of baseline
  • Glucose monitoring (neonates/infants prone to hypoglycaemia on bypass)
  • Maintain haematocrit >25-28% on bypass
• Surgical repair: patch closure or primary suture
• Post-bypass (coming off CPB):
  • Rewarming to normothermia
  • Volume and vasopressor support as needed (vasodilators like nicardipine or nitroprusside for hypertension; dopamine for low cardiac output)
  • TOE to confirm successful closure (no residual shunt), RV/LV function, no new wall motion abnormalities
  • Reverse heparin with protamine (1 mg per 100 IU heparin) - watch for hypotension/pulmonary vasoconstriction with protamine

5. For Device Closure in Catheterisation Lab:

• General anaesthesia (ETT or LMA - depends on airway assessment)
• Supine with TOE probe in-situ throughout to guide device deployment and check for residual leak, position, and function of adjacent structures (mitral valve, coronary sinus, pulmonary veins)
• No CPB, but crash bypass capability must be available in lab
• Air precautions still apply until device is deployed and ASD closed

Post-operative Management

Airway Extubation:

• Awake extubation only if intubation was difficult - the same difficulties recur if re-intubation is needed
• For routine surgical cases: fast-track extubation (in theatre or early ICU) is increasingly standard for ASD repairs
• For Stickler + PRS babies: extend intubation in ICU if there is any concern about upper airway patency post-extubation
• Have full re-intubation equipment and video laryngoscope at bedside during extubation

Post-operative Monitoring:

• Cardiac ICU admission: continuous monitoring of SpO2, invasive BP, CVP, ETCO2 (if still intubated), urine output (0.5-1 mL/kg/hr)
• Watch for:
  • Residual shunt (new murmur, desaturation) - reassess with echo
  • Arrhythmias (junctional rhythm, atrial arrhythmias common post-ASD repair due to atrial manipulation)
  • Low cardiac output syndrome: especially 6-12h post-CPB; treat with inotropes (dopamine, dobutamine), milrinone if RV dysfunction
  • Pulmonary hypertensive crisis (if pre-existing PAH): give 100% O2, inhaled nitric oxide (iNO), IV sildenafil/prostacyclins; avoid painful stimuli without adequate analgesia
  • Bleeding and coagulopathy post-CPB
  • OSA/upper airway obstruction post-extubation (Stickler PRS): lateral/prone positioning, nasopharyngeal airway, supplemental oxygen, pulse oximetry monitoring overnight

Analgesia (Post-ASD Repair):

• Multimodal: paracetamol + NSAID + regional technique
• Regional block options (per Karuppiah et al., J Cardiothorac Vasc Anesth 2021, PMID 32758407):
  • Sternotomy: subcutaneous bupivacaine infiltration
  • Mini-thoracotomy: serratus anterior plane block or erector spinae plane block (11/15 patients in the review)
• Minimise systemic opioids post-operatively in Stickler babies with PRS/OSA features (respiratory depression risk)
• Dexmedetomidine is a useful adjuvant: analgesia + sedation + no respiratory depression (as used in the Freeman-Sheldon syndrome ASD case, PMID 37438578)

Special Combined Considerations Summary

Key Summary Points

1. Airway is the first priority - plan as for any Stickler baby with potential PRS; have full difficult airway equipment
2. Maintain spontaneous ventilation during inhalational induction until airway confirmed secured
3. No N₂O - risk of air embolism and PAH exacerbation
4. All IV lines must be rigorously air-free - paradoxical embolism through the ASD
5. High FiO₂ + low PVR strategy - prevent pulmonary hypertensive crisis
6. TOE guidance throughout (especially for device closure)
7. Awake extubation - never extubate deep if airway was difficult
8. Post-op monitoring for OSA - extended ICU monitoring, lateral/prone positioning, avoid opioid excess
9. Regional analgesia (serratus anterior or erector spinae block) to minimise opioid requirements
10. Document the difficult airway - update anaesthetic records and fit medical alert bracelet

Key References

• Zimmermann et al., Anesth Analg 2021 - 502-patient Stickler airway series: receding mandible + cleft palate as risk predictors (PMID 31856005)
• Akhtar et al., 2024 - Stickler Type III PRS with cardiac defects; ~20% of PRS have CHD (PMID 38440550)
• Karuppiah et al., J Cardiothorac Vasc Anesth 2021 - Regional analgesia for paediatric surgical ASD closure (PMID 32758407)
• OpenAnesthesia - Atrial Septal Defects - Haemodynamic goals and monitoring
• Kanski's Clinical Ophthalmology 10th ed. - Stickler syndrome: PRS features, ocular fragility
• The Harriet Lane Handbook 23rd ed. - Acyanotic CHD clinical features