What is the protocol for conducting a lactate and ammonia test during exercise to diagnose exercise intolerance due to metabolic disorders?

Protocol for Exercise Intolerance Lactate and Ammonia Testing

The standard protocol for conducting a lactate and ammonia test during exercise involves a non-ischemic forearm exercise test (NIFET) at 70% of maximal voluntary contraction for 30 seconds, with blood sampling before, immediately after, and during recovery to diagnose metabolic myopathies causing exercise intolerance.

Test Preparation and Setup

• Patient should be in a rested state prior to testing, as baseline measurements of lactate and ammonia are critical for accurate interpretation 1
• Arterial blood sampling is considered the gold standard for lactate measurement, though properly arterialized venous blood is acceptable 2
• Equipment needed: dynamometer for measuring grip strength, timer, blood collection supplies for serial sampling 3

Testing Protocol

• Determine the patient's maximal voluntary contraction (MVC) using a dynamometer 3
• Have the patient perform isometric exercise at 70% of their MVC for 30 seconds under non-ischemic conditions 3
• Collect blood samples at the following time points:
  • Baseline (pre-exercise) 3
  • Immediately after exercise completion 3
  • At 5,10, and 15 minutes during recovery 4

Sample Analysis

• Measure blood lactate, lactate/pyruvate ratio, and ammonia concentrations in all collected samples 4
• Normal response in healthy subjects shows:
  • Nearly fourfold increase in lactate levels after exercise 3
  • Lactate and ammonia levels that peak immediately post-exercise 5
  • Progressive decrease in lactate and ammonia between 5-15 minutes of recovery in 98% of normal subjects 4

Interpretation of Results

• Abnormal patterns suggesting metabolic myopathies include:
  • No significant lactate increase after exercise (seen in glycogen storage diseases) 3
  • Severe hyperammonemia (>141 μmol/L) strongly suggests glycogen storage disease 6
  • Disparate lactate responses or abnormally high resting lactate levels may indicate mitochondrial myopathy 3
  • Failure of lactate, lactate/pyruvate ratio, or ammonia to decrease between 5-15 minutes of recovery 4

Advantages of Non-Ischemic Testing

• The non-ischemic protocol is safer than traditional ischemic testing, particularly for patients with suspected glycogenosis where ischemic conditions could induce rhabdomyolysis 3
• Provides specific and efficient screening for patients with exercise intolerance 3
• Shows excellent sensitivity for glycogenolysis defects and partial sensitivity for mitochondrial disorders 3

Clinical Applications

• This test helps differentiate between various causes of exercise intolerance when standard cardiopulmonary exercise testing (CPET) is inconclusive 2
• Particularly useful for diagnosing metabolic myopathies that may not be evident from resting measurements 2
• Can guide further diagnostic testing such as muscle biopsy when abnormal patterns are detected 4

Important Considerations

• Mild hyperammonemia (94-141 μmol/L) without other abnormalities is likely non-specific and not indicative of muscle disease 6
• Exercise alters the distribution of ammonia and lactate between plasma and red blood cells, which can affect interpretation if not accounted for 7
• The lactate response differs from the ammonia response during constant exercise, with lactate increasing continuously at higher exercise intensities while ammonia increases more gradually 5