Spinal Muscular Atrophy (SMA)

SMA (Spinal Muscular Atrophy)

• Type 1 "Werdnig Hoffmann" presents in infants
• Muscles are properly formed, but nerves do not function, leading to muscle weakness and atrophy
• The SMN1 gene mutation leads to insufficient SMN protein production, causing motor neuron loss
• Motor neurons are lost because they no longer receive signals from the brain
• It is a recessive genetic disease
• Initial symptoms can be observed in utero
• Usually diagnosed by 6 months
• Without treatment, death occurs by age 3
• Symptoms include:
  • Floppy baby appearance
    • Poor muscle tone
  • No motor function
    • Sensory function is still present
    • Cannot move but can feel
  • Legs are often sprawled out like a frog
    • Knees and arms are bent

SMA Medications

• Spinraza (nusinersen) is a medication that increases SMN protein production
  • It is administered via injection into the CSF with three loading doses spaced two weeks apart
  • A fourth dose is given 30 days later, followed by repeat doses every 4 months
  • The first year of Spinraza treatment costs $750,000, followed by $375,000 per year
• Zolgensma (onasemnogene abeparvovec-xioi) is a gene therapy which replaces the non-working or missing SMN1 gene, it is approved for children under two years old
  • Administered via IV infusion over 1 hour, only one dose is needed for life
  • The cost is $2.125 million for a single dose

Muscular Dystrophy

• It is a genetic disease with many variations
• Muscles are non-functional, but nerves are properly formed
• Duchenne’s Muscular Dystrophy is a sex-linked recessive condition
  • This means it primarily affects males and does not manifest in infancy
• Symptoms include:
  • Loss of calf and hip muscle function
  • Muscles appear large and bulky but consist of fat
  • Walking becomes difficult
  • Initial difficulty walking up steps, progresses to walking on toes, waddling, and struggling to rise from a seated position
• Diagnosis is typically made by age 5 or 6, and wheelchair assistance is needed by age 10-15
• Outcome
  • Life expectancy is extended with a trach and vent
  • Death typically occurs before age 20 without intervention

ECMO/ECLS (Extracorporeal Membrane Oxygenation/Extracorporeal Life Support)

• Extracorporeal means occurring outside the body
• A modified version of cardiopulmonary bypass, but for an extended period
• Can be implemented in emergencies or as a planned procedure
• It supports the heart and lungs through VA (veno-arterial) support or just the lungs using VV (veno-venous) support
• This therapy is not curative but allows the body to rest and recover

How ECMO Works

• Cannulas are inserted into the patient's vessels to drain blood to the ECMO pump
• The pump circulates the blood through an oxygenator membrane for gas exchange
• The oxygenated blood is then returned to the patient via cannulas in their vessels

ECMO Flow: Centrifugal Pump

• The magnetic pump "spins" at a set rate (rpm) to generate pump flow (L/min)
• In VA ECMO flow, cardiac output is provided
• In VV ECMO flow, just blood to oxygenator is controlled
• Pre-pump pressure is negative, while post-pump pressure is positive
• Centrifugal ECMO pumps depend on preload and afterload and require proper circulating volume
  • Chugging is when there is no fluid moving through the pump
• High native blood pressure can interfere with ECMO pump flow; sedation, vasodilators, or pressors may be considered

ECMO Sweep

• A membrane acts as a lung, removing CO2 and supplying O2 to venous blood
• ECMO replaces the need for native lung function in both VV and VA configurations
• The "sweep gas" is a blend of air and oxygen
  • FiO2 in the sweep gas supplies O2 to blood
  • The sweep gas flow removes CO2 from the blood

VA (Veno-Arterial) ECMO

• Used for full cardiopulmonary support
• Venous Cannula:
  • Large, drains deoxygenated blood from patient to pump
    • Large patients may require multiple cannula insertions for increased flow
  • Catheter insertion is percutaneous through the RIJV or FA or directly into the right atrium
• Arterial Cannula:
  • Smaller, returns oxygenated blood from pump back to body
  • Percutaneous insertion via RCA or IVC or directly into the aorta.
• VA ECMO "bypasses" the heart by providing both cardiac output and lung support
• Pump flow determines cardiac output
  • Increased flow raises both CO and BP
  • if cardiac arrest do not do compressions and increase pump flow
• The lungs are at rest with the sweep gas

VV (Veno-Venous) ECMO

• Used for full pulmonary support, not cardiac
• Blood is drawn through a dual-lumen catheter from the IVC and SVC, and returned to the right atrium
• Monitor for recirculation where oxygenated blood is pulled into the venous circulation and does not enter the right atrium
  • If mixed venous sats > 65-75%, recirculation is occurring
    • Reduce flow

SpO2 and ECMO Support

• native heart provides cardiac output
• increasing flow will not increase CO or BP
• BP will be pulsatile if cardiac arrest compressions are needed
• SpO2 is typically lower on VV ECMO than VA ECMO with native function
• Pulsatile BP is only achieved due to cardiac function

Who Can Use ECMO

• Neonatal inclusion criteria:

  • 34 weeks gestation, >2000g birth weight

  • No intracranial hemorrhage, or less than grade 1
  • Controllable bleeding and reversible lung disease
  • Mechanical ventilation required for less than 10-14 days
  • No other conditions rendering ECMO use futile shown by central nervous system dysfunction
• Exclusion criteria:
  • Lethal congenital anomalies, irreversible underlying condition, incompatible with a normal healthy childhood, incurable diseases, cancer or AIDS

  • 10 days of ventilation puts survival rate at 22%

  • Chronic multi-organ dysfunction
  • Irreversible brain damage

ECMO Ventilation Strategies

• Pre-ECMO settings are high, and ECMO should start early if OI > 40
• Paralytics and barotrauma should be considered
• During ECMO, the ventilator should be on a resting setting to allow the lungs to rest and avoid barotrauma
• Pulmonary toilet should be provided
• Rescue settings should be similar to setting on pre-ecmo stage
• Post-ECMO ventilator settings are not set to pre ECMO settings, requiring the patient to stay under ECMO

ECMO Complications

• Bleeding
• Accidental decannulation
• Stroke and clotting resulting in malfunctioning equipment

The Classification of Pneumonia

• Causative pathogen and clinical setting can be responsible for pneumonia
• General PNA terminology:
  • Double pneumonia: affecting both lungs
  • Walking pneumonia: a less severe form
  • Defined by location in the lungs: bronchopneumonia, lobar pneumonia and interstitial pneumonia

Community-Acquired Atypical Pneumonia Overview

• A subacute clinical representation has a variety of pulmonary and extrapulmonary findings
• Mycoplasma is the most common cause
• Causes similar findings in both bacterial and viral pneumonia
• A cough is present with small white mucus
• Atypical pneumonia can not be identified via standard bacteriologic tests
• Sputum is present and there is moderate elevation of white cell count
• Lack of alveolar consolidation of exudate can take place

Specific Pneumonia

• Coxiella burnetti: Gram-negative bacterium that causes Q fever
• Chlamydia: pneumonia, psittaci and trichromatic
• Viruses: 50% of all pneumonias are associated with community-aquired atypical pneumonia

Viruses associated with atypical pneumonia

• Respiratory syncytial, parainfluenza, influenza A/B, adenovirus, and human metapneumovirus are viruses associated with atypical pneumonia
• Paramyxovirus is related to mumps and rubella
• Influenza A and B are the most common cause of viral respiratory tract infections

Pneumonia in the Hospital Setting

• Also called hospital-associated and nosocomial pneumonia
• Occurs 48 hours post-hospital admission
• Pseudomonas aeruginosa, MRSA or MSSA
• Refers to patients who have recently been in the hospital with antibiotic therapy, chemotherapy and wound care

Aspiration Pneumonia

• 3 forms: toxic injury, obstruction, infection
• Caused by gastric acid, foreign materials or fluids
• Assumed as cause of nearly all cases of anaerobic pulmonary infections

Fungal Pathogens

• Coccidioidomycosis: spores caused by inhalation and can come from the southwest region
• Blastomycosis: Is an exposure of the lungs with sputum
• Candida albicans: Thrush and high nitrogen content
• Aspergillus: Soil debris

Immunocompromised Host

• Caused by CMV
• Pneumocystis is common among those with aids as well as chicken pox

Associated manifestations with PNA

• Alveolar consolidation as well as capillary membrane thickness
• Air can go through bronchial washings if intubated and there is need for section
• Test through sputum sampling and chest x-ray for alveolar- cap membrane analysis

Lung Volume Flow

• Measured through VT with its two forms: Alveolar volume and dead space
• A normal Vd is 25-40% through VT
• A spontaneous breathing trial will take place with specific measurements that need to be known
• Rate is based on minute vs depth through resistance
• There is evaluation of oxygenation with arterial oxygen as well pulse rate as well

Tidal volume

• Tidal volume is VT with a normal range being 5 to 8
• Dead space is the conductive airway

Oxygenation Measurements

• Monitoring is found through the ratio and oxygen delivery

Lung Lactate

• Tissue is not normal due to 2 percent and an arterial reading