Osteogenesis Imperfecta

Introduction

• OI is a heterogeneous connective tissue disorder that is characterized by bone fragility and progressive skeletal deformities due to a disorder in collagen production.^1-7
• Life expectancy, frequency and severity of fractures, skeletal deformities, and degree of disability vary depending on OI type.^1-6
  • Clinical features range from osteopenia with a mild predisposition to fractures to severe skeletal deformities with multisystem effects resulting in death.^1-6

Epidemiology

• OI occurs in 1 in 10,000-20,000 live births.^1,3,4,7
• There are four main types of OI, but 17 types have been described, with additional types added as new genetic variations are discovered.^1-5
  • Type I – Most common (60% of cases) and the mildest form. These patients are of normal stature and may have blue sclerae, hearing loss, and mild bone fragility.
  • Type II – 10% of cases and the most severe form. This type is evident in utero or at birth and often results in neonatal death.
  • Type III – 20% of cases and a severe form. These patients have progressive skeletal deformities and frequent fractures, very short stature, hearing loss, and dentinogenesis imperfecta. Death may occur in childhood or adolescence due to cardiopulmonary complications.
  • Type IV – Less than 10% of cases and moderate in severity. These patients have moderate bone fragility, resulting in frequent fractures, short stature, hearing loss, and dentinogenesis imperfecta.

Pathophysiology

• OI is a disorder of connective tissue resulting from mutations in genes that code for type I collagen.^1,2,4-6
  • These mutations may be inherited in an autosomal dominant or autosomal recessive manner or may be spontaneous.^2,4-6
  • 90% of OI patients have mutations of the pro-⍺₁ or pro-⍺₂ chains of type I collagen (COL1A1 or COL1A2) genes.^1,2,4,5
  • Type I collagen is the principal matrix protein in bone, dentin, sclerae, and ligaments.^1,5

Clinical Presentation

• Clinical features of OI vary depending on the OI type. Associated clinical presentations include:
• Neurologic
  • Most OI patients have age-appropriate cognition.
  • Hearing Loss – Hearing loss is due to skeletal deformities of the inner ear.^1,2,4-6
  • Basilar invagination – Basilar invagination is a serious complication of OI. It is described as the upward displacement of basilar and condylar portions of the occipital bone, causing an infolding of the foramen magnum and leading to a translocation of the upper cervical spine into the brainstem.^1,4
  • Symptoms of basilar invagination include occipital headaches, limitations of neck range of motion due to weakness, proprioception disturbances, paresthesias, or signs of increased intracranial pressure.
• Head/Neck/Airway
  • Patients with OI may have difficult mask ventilation and/or endotracheal intubation due to facial dysmorphism, decreased cervical spine mobility, concern for cervical spine and maxilla/mandible fracture with airway manipulation, thoracic skeletal deformities, and brittle dentition.^1-4,6
• Cardiovascular
  • Kyphoscoliosis and/or thoracic skeletal deformities may lead to right ventricular dysfunction and pulmonary hypertension.⁴
  • Since type I collagen makes up 85% of cardiac muscle, decreased collagen diameter and amount leads to alterations in the structure and mechanics of the myocardium.⁴
  • A majority of OI patients develop valvular regurgitant lesions. Mitral valve prolapse, aortic regurgitation, and aortic root dilation are observed.²
• Respiratory
  • OI patients may have restrictive lung disease and pulmonary hypertension due to kyphoscoliosis or thoracic skeletal deformities.^2,4,5
• Musculoskeletal
  • Musculoskeletal manifestations include a propensity for fracture (sometimes with innocuous trauma) and progressive skeletal deformities.
  • Skeletal deformities include short stature, scoliosis, kyphosis, bowed long bones, head and facial dysmorphism, genu valgum, flat feet, hypermobile joints, and osteopenia.^1-7
• Hematology
  • Increased capillary fragility, decreased platelet retention and aggregation, and decreased factor VIII production lead to a hemorrhagic diathesis.^1-4,6
  • Platelet dysfunction exists despite a normal platelet count, likely due to an impairment in platelet-endothelial cell adhesion.^1,6
• Endocrine
  • An increased serum thyroxine concentration associated with an increase in oxygen consumption occurs in at least 50% of OI patients.⁶

Treatment

• The goals of treatment are to maximize function and to minimize deformity and disability. Physical therapy, medical therapy, and surgery are the mainstays of treatment.⁵
• Medical Therapy
  • Treatment with antibone-resorptive bisphosphonates (e.g., pamidronate) can decrease pain, lower fracture incidence, and improve mobility.^1,2,5,6
• Surgical Treatment
  • Early surgical reinforcement of long bones is the standard treatment.^1,5
  • OI patients often present for urgent surgery due to fractures.

Anesthetic Considerations

Preoperative Considerations

• Medical History
  • A medical history should elicit the type of OI, exercise tolerance or functional capacity, symptoms that may indicate basilar invagination or restrictive lung disease, history of fractures with precipitating causes, and any complications with prior surgeries.
• Physical Exam
  • An airway evaluation should include mouth opening, neck range of motion, symptoms of cranio-vertebral junction pathology with neck extension, and dentition.
  • A musculoskeletal examination should include range of motion of neck and extremities, fixed flexion/extension of extremities, and chest wall deformities.
  • Signs that indicate a bruising or bleeding tendency should be noted.
• Labs and Studies
  • A complete blood count, coagulation studies, and type and screen may be indicated due to an increased risk of surgical bleeding.^1,2,4,6
    • Approximately 30% of OI patients have abnormal bleeding times.²
  • An echocardiography may be indicated, especially in patients with severe OI types, with decreased functional capacity, and/or with scoliosis or thoracic skeletal deformities.
    • It may demonstrate pulmonary hypertension, ventricular dysfunction, mitral valve prolapse, aortic regurgitation, or aortic root dilation.^1,2,4
• OI patients may have preoperative anxiety due to frequent surgeries. Anxiolytic medications or the involvement of child life specialists may be helpful.

Intraoperative Considerations

Anesthetic Considerations:

• Monitors – Standard American Society of Anesthesiologists monitors should be used. If there is concern for fracture with inflation of a noninvasive blood pressure cuff, an arterial line may be placed.^5,6
  • If a standard noninvasive blood pressure cuff is utilized, consider less frequent cycling if hemodynamics permits.⁵
• Airway – OI patients may be a difficult mask ventilation and/or endotracheal intubation due to head and facial dysmorphism, short neck, decreased cervical spine mobility, thoracic skeletal deformities, and brittle dentition.^1-4,6
  • In-line stabilization of the cervical spine should be maintained throughout airway management. A supraglottic airway or endotracheal tube (ETT) may be utilized depending on the patient and procedure.
  • If mask ventilation requires significant neck extension or forceful pressure on the maxilla or mandible, a supraglottic airway may be placed.⁵
  • Cervical spine fracture or atlantoaxial subluxation may occur with excessive neck manipulation or extension. Fracture of the maxilla or mandible may occur with pressure.^4-6
  • Video laryngoscopy or fiberoptic intubation should be considered if placing an ETT to minimize cervical spine extension.^4,6
  • Dental guards may be used if brittle dentition is present.
• IV access – The use of a tourniquet to facilitate IV placement may result in fracture.1 An ultrasound may be employed to facilitate IV placement without using a tourniquet or gentle manual circumferential pressure may be applied in place of a tourniquet.
• Medication Considerations – Avoidance of succinylcholine is recommended, as fasciculations may result in fractures.^5,6
  • In cases when succinylcholine is necessary, pretreatment with a nondepolarizing muscle relaxant will attenuate fasciculations.
  • In patients with severe skeletal deformities or with recurrent fractures that cause immobility, succinylcholine may result in hyperkalemia due to the upregulation of acetylcholine receptors.
• Temperature Management – Abnormal temperature homeostasis may result in intraoperative hyperthermia that may be accompanied by tachycardia and metabolic acidosis. Surface cooling is usually effective in restoring thermal homeostasis.^2,3,5,6
  • If hyperthermic, antimuscarinic medications such as atropine and glycopyrrolate should be used judiciously.^2,3
  • OI is not associated with malignant hyperthermia (MH), although cases of MH have been reported in OI patients. As such, one should consider a separate diagnosis of MH if the clinical picture permits.^2,3,5,6
• Regional Anesthesia – Neuraxial and regional anesthesia may be utilized.^6,7
  • There is insufficient evidence to validate or refute the risks of neuraxial and regional anesthesia in OI patients. However, the potential for difficult placement due to anatomical abnormalities, increased surgical bleeding, and platelet dysfunction should be considered.^6,7
  • If performing neuraxial anesthesia, platelet count and coagulation studies should be obtained, but one must consider that platelet function abnormalities exist despite a normal platelet count.^6,7
  • If performing a peripheral nerve block, nerve stimulation may lead to contraction-induced fractures; therefore, ultrasound guidance is preferred.

Surgical Considerations:

• Positioning – Extreme care must be taken when positioning OI patients, as even minimal pressure or trauma may lead to fractures. Padding is encouraged given ligamentous laxity and to decrease pressure points.^1-7
• Tourniquet Use – If a tourniquet is indicated on the operative extremity, the risk of iatrogenic fracture with the tourniquet must be weighed against increased surgical bleeding without the use of the tourniquet. Consider a lesser degree of tourniquet inflation if it is to be used.
• Blood Loss – Patients with OI may exhibit increased surgical bleeding, so arrangements to transfuse blood products may be warranted.^1-4,6

Challenges such as difficult airway, difficult IV access, failed neuraxial placement, perioperative fracture, and significant blood loss are more common in patients with a severe OI type (Type III) than with a milder OI type (Type I).¹

Postoperative Considerations

• Emergence and Extubation – The decision to extubate postoperatively should be based on comorbidities. Most patients without restrictive lung disease can be extubated and recover in the post-anesthesia care unit.
• Pain Management – Nonopioid analgesics, opioids, muscle relaxers, and neuraxial or peripheral nerve catheters may be utilized to manage pain postoperatively.