6.1 Open-Circuit Nitrogen Washout Method: Principles, Equipment, and Calculation

6.1 Open-Circuit Nitrogen Washout Method: Principles, Equipment, and Calculation

Determination of absolute lung volumes—specifically Functional Residual Capacity (FRC), Residual Volume (RV), and Total Lung Capacity (TLC)—is essential for differentiating between restrictive lung disorders, obstructive lung diseases, and mixed physiological patterns. Because spirometry can only measure gas volumes that can be exhaled (such as Vital Capacity and Tidal Volume), it cannot directly measure the gas remaining in the lungs at the end of a normal exhalation (FRC) or maximum exhalation (RV).

One of the classical, widely utilized techniques for quantifying absolute lung volume is the Open-Circuit Nitrogen (N2) Washout Method (historically established by Darling, Cournand, and Richards). This chapter provides an exhaustive review of the physiological principles, system hardware, calculation mechanics, tissue nitrogen corrections, and clinical quality assurance standards required for the NBRC CPFT examination.

---

Physiological Principles and Assumptions

The open-circuit nitrogen washout method relies on washing out the resident nitrogen ($N_2$) gas stored within the patient's lungs by inspiring 100% pure medical oxygen ($O_2$). Nitrogen is an physiologically inert gas under ambient conditions; it does not participate in metabolic gas exchange and remains in equilibrium between atmospheric air and the alveoli.

Baseline Alveolar Nitrogen Assumption

When a patient breathes room air at sea level, the inspired air consists of approximately 78.08% nitrogen, 20.95% oxygen, 0.93% argon, and trace gases. Inside the alveoli, inhaled gas becomes fully saturated with water vapor ($P_{H2O} = 47 \text{ mmHg}$ at $37^\circ\text{C}$) and mixes with carbon dioxide ($P_{CO2} \approx 40 \text{ mmHg}$).

Under normal physiological equilibrium while breathing ambient room air, the initial fractional concentration of alveolar nitrogen ($F_{A,N2\text{ initial}}$) is assumed to be between 78% and 81%, with 79% ($0.79$) established as the standard physiological constant in clinical pulmonary function testing.

$\text{Total Volume of } N_2 \text{ in Lungs at FRC} = FRC \times F_{A,N2\text{ initial}} = FRC \times 0.79$

The Washout Process

During open-circuit washout, the patient is connected to a non-rebreathing valve circuit at end-tidal expiration (at exact FRC). The patient inspires 100% $O_2$ from a pressurized demand valve or reservoir bag and exhales into a volume-measuring device (such as a dry-rolling seal spirometer, water-seal spirometer, or digital mass-flow pneumotachometer) integrated with a rapid-responding nitrogen analyzer.

As 100% $O_2$ enters the lungs, each breath dilutes and flushes out alveolar $N_2$. Exhaled gas is collected and measured until the alveolar $N_2$ concentration falls to near zero.

---

Step-by-Step Clinical Testing Protocol

Executing a valid nitrogen washout procedure requires strict adherence to standardized clinical protocols:

1. Patient Preparation & Positioning: The patient sits upright in an ergonomic chair with feet flat on the floor. A secure nose clip is applied, and the patient breathes ambient room air through a mouthpiece to establish a regular, stable resting end-expiratory baseline (Tidal Volume and FRC stability).
2. Circuit Connection at FRC: At the exact end of a normal tidal exhalation (end-expiratory level), the directional valve switches the patient from room air to the 100% $O_2$ supply line. Timing is critical: connecting the patient above or below true FRC introduces severe volume calculation errors.
3. 100% Oxygen Breathing: The patient continues normal tidal breathing of 100% $O_2$. The volume of exhaled gas ($V_E$) and the instant-by-instant exhaled $N_2$ concentration are continuously recorded.
4. Monitoring End-of-Test Criteria: Under the 2023 ATS/ERS lung volume update, washout continues until the end-tidal tracer (N$_2$) concentration falls below 1/40th of its starting concentration for at least 3 consecutive breaths. Starting from a room-air baseline of about 79% N$_2$, one-fortieth is approximately 2.0% N$_2$. The older flat "below 1.5%" threshold is the retired 2005 criterion; it is still printed in many review books, so recognize both, but apply the 1/40th rule. A rise in N$_2$ greater than 1% during washout signals a leak, not completion.
5. Maximum Time Limit: In healthy subjects, nitrogen washout completes within 3 to 4 minutes. In severe airflow obstruction, delayed gas mixing and slow-emptying compartments prolong it substantially. If the end-tidal N$_2$ never reaches the 1/40th end point, the test is terminated at a practical cap of about 7 minutes (420 seconds) and the incomplete washout is documented, because the reported FRC will underestimate the true value.

---

Tissue Nitrogen Excretion Correction

A critical requirement on the CPFT examination is accounting for tissue nitrogen excretion. Nitrogen is not only present in alveolar gas; it is also dissolved in blood plasma, body tissues, and fat compartments throughout the body.

When a patient breathes 100% $O_2$, the partial pressure of nitrogen in the alveoli drops dramatically toward zero ($P_{A,N2} \approx 0 \text{ mmHg}$). This creates a steep partial pressure gradient between the systemic venous blood/tissues and the alveoli. Consequently, dissolved nitrogen diffuses out of body tissues into the capillary blood, travels to the lungs, and excretes into the alveoli, where it mixes with exhaled gas.

If this tissue-derived nitrogen is not subtracted from the total collected exhaled $N_2$, the system will assume the extra nitrogen came from the lungs, leading to a substantial overestimation of FRC.

The Standard Correction Factor

Under standard clinical protocols, tissue nitrogen excretion is calculated as a constant rate of 0.04 liters per minute (40 mL/min) of 100% $O_2$ breathing:

$V_{\text{tissue } N2} = 0.04 \text{ L/min} \times t_{\text{washout (minutes)}}$

• Example: If a nitrogen washout test lasts 5.0 minutes, the total tissue nitrogen excretion deduction is: $V_{\text{tissue } N2} = 0.04 \text{ L/min} \times 5.0 \text{ min} = 0.20 \text{ Liters (200 mL)}$

---

Mathematical Derivation and FRC Calculation Formula

The fundamental calculation of FRC via nitrogen washout rests on mass balance: the total volume of nitrogen exhaled from the lungs equals the volume of nitrogen originally present in the lungs at FRC minus the tissue nitrogen contribution.

$\text{Total } N_2 \text{ Exhaled} = \left( FRC \times F_{A,N2\text{ initial}} \right) + V_{\text{tissue } N2} - \left( FRC \times F_{A,N2\text{ final}} \right)$

Rearranging the mass balance equation to solve for $FRC$ (and expressing volumes in BTPS conditions):

$FRC_{N2} = \frac{V_E \times (F_{\bar{E},N2\text{ final}} - F_{\bar{E},N2\text{ initial}}) - (0.04 \times t)}{F_{A,N2\text{ initial}} - F_{A,N2\text{ final}}} \times \text{BTPS Factor}$

Where:

• $V_E$: Total expired volume collected during the washout period (Liters STPD).
• $F_{\bar{E},N2}$: Mixed expired nitrogen fractional concentration.
• $F_{A,N2\text{ initial}}$: Initial alveolar nitrogen fraction (standard baseline = $0.79$).
• $F_{A,N2\text{ final}}$: Final alveolar nitrogen fraction at end of test (e.g., $0.01$ or $0.015$).
• $t$: Total duration of 100% $O_2$ breathing in minutes.

Derivation of RV and TLC

Once $FRC_{N2}$ is calculated, Residual Volume ($RV$) and Total Lung Capacity ($TLC$) are derived using spirometric subdivisions measured during the same testing session:

$\text{Residual Volume (RV)} = FRC_{N2} - \text{Expiratory Reserve Volume (ERV)}$ $\text{Total Lung Capacity (TLC)} = FRC_{N2} + \text{Inspiratory Capacity (IC)}$ $\text{Alternatively: } TLC = RV + \text{Slow Vital Capacity (SVC)}$

---

Equipment Hardware and Sensor Calibration

Accurate open-circuit nitrogen washout testing requires specialized hardware designed for high-frequency gas sampling and volume integration:

1. Nitrogen Analyzer: Uses an electrical discharge tube (emission spectrograph) or mass spectrometer to measure $N_2$ concentrations continuously. High-precision emission spectrographs pass exhaled gas through a low-pressure tube where an electric voltage excites $N_2$ molecules, emitting purple-violet light. The intensity of light at specific wavelengths ($310-480 \text{ nm}$) is proportional to the $N_2$ concentration. The analyzer must have a rapid response time ($< 50 \text{ milliseconds}$) to resolve breath-by-breath alveolar concentrations.
2. Demand Valve & Oxygen Source: Delivers 100% medical grade $O_2$ at low resistance and sufficient peak inspiratory flow ($>120 \text{ L/min}$) without entraining ambient air.
3. Flow/Volume Sensor: A heated pneumotachometer or dry-rolling seal spirometer measures exhaled volume continuously. Calibration must be verified using a 3.0-Liter calibration syringe over a range of flows ($0.5 \text{ L/s}$ to $12.0 \text{ L/s}$).
4. N2 Analyzer Calibration: Two-point gas calibration is mandatory prior to testing:
   • Zero Gas: 100% pure $O_2$ ($0.0% \text{ } N_2$).
   • Span Gas: Room air ($79.0% \text{ } N_2$) or a certified calibration standard ($78.08% \text{ } N_2$).

---

ATS/ERS Acceptability and Repeatability Criteria

To ensure valid physiological measurements, ATS/ERS guidelines specify strict performance standards:

• Stable Baseline: Resting tidal end-expiratory level must be stable for at least 4 to 5 breaths prior to switching into 100% $O_2$.
• No Leaks: The exhaled $N_2$ concentration curve must decline smoothly without abrupt upward spikes.
• Repeatability Standard: At least two acceptable trials must be performed. The calculated FRC values from the two trials must agree within 10% of each other (or within $200 \text{ mL}$ of the mean value).
• Mandatory Rest Interval: Wait at least twice the duration of the washout (a 15-minute interval is the traditional rule of thumb) breathing room air between repeat trials. This interval allows dissolved nitrogen to re-diffuse into tissues and alveolar gas to re-equilibrate back to the baseline 79% concentration. In patients with severe obstructive lung disease, this rest period should be extended to 20–30 minutes.

---

Common Technical Errors and Troubleshooting

Recognizing technical artifacts is a major focus of Domain II on the CPFT exam:

1. Systemic Circuit Leaks

• Symptom: During washout, the nitrogen concentration abruptly spikes upward from low levels (e.g., jumping from 2% to 15% or 20%).
• Cause: Ambient room air (which contains 78% $N_2$) enters the system via a loose mouthpiece seal, unclipped nose, or disconnected tubing joint.
• Effect: Massive overestimation of FRC due to false addition of exogenous nitrogen.
• Action: Terminate the trial, correct the leak site, wait at least twice the elapsed washout time, and retest.

2. Perforated Tympanic Membrane (Eardrum Air Leak)

• Symptom: Persistent elevated baseline $N_2$ concentration that plateauing above 2% despite prolonged 100% $O_2$ breathing.
• Cause: Air enters the nasopharynx via an unoccluded perforated eardrum or Eustachian tube.
• Action: Insert silicone earplugs prior to repeating the test.

3. Improper Valve Connection Timing

• Cause: Switching the patient to 100% $O_2$ above FRC (at end-inspiration) or below FRC (after forced exhalation).
• Effect: Connecting above FRC overestimates true resting FRC; connecting below FRC underestimates true resting FRC.