ALS Presenting as Hypercarbic Respiratory Failure

Thanks to Dr. Mayo for her presentation today of hypercarbic respiratory failure in an elderly male who was later diagnosed with amyotrophic lateral sclerosis (ALS).

One way to think about the elimination of carbon dioxide is:

  • "won't breath" - CNS
  • "can't breath" - PNS, respiratory muscles, chest wall, pleura, upper airway
  • "can't breath enough" - lungs

This allowed us to think through some common causes.

  • Decreased central drive - sedative medications, stroke, OSA
  • Decreased respiratory or thoracic cage function - spinal cord injury, ALS, Guillain-Barre, phrenic nerve injury, Myasthenia Gravis, Lambert Eaton, tetanus, organophosphate poisoning, neuromuscular blockade, metabolic disorders (low Phos, Mg; hyper-hypothyroidism)
  • Increased dead space - PE, severe pulmonary vascular disease, dynamic hyperinflation (COPD, severe asthma), end stage interstitial lung disease
  • Increase CO2 production - fever, thyrotoxicosis, increased catabolism, metabolic acidosis
  • Multifactorial - vocal cord paralysis, severe laryngea/tracheal disorders, foreign body aspiration,obstructive goiter

In this instance, pulmonary function tests (PFTs) and maximal inspiratory/expiratory pressures (MIPs and MEPS respectively) were key. Remember that neuromuscular disorders such as ALS demonstrate a predominately restrictive pattern on PFTs which means that patients may have a normal FEV1 and FEV1/FVC ratio. After diagnosis, regular spirometry (generally accepted to be every 3 months after diagnosis) is important to monitor progression. A recent review article highlights that two large trials (EMPOWER, BENEFIT-ALS) and the ALS trial database (PRO-ACT) found that the rate of decline in FVC predicts the liklihood of death. Another recent study showed that twitch trans-diaphragmatic pressure is the most powerful biomarker for mortality. But, that sniff nasal inspiratory pressure (SNIP) is an excellent correlate. And that a VC within a normal range suggests a good prognosis. Ultimately, there is no one single test which predicts all.