1. Introduction

Monitoring of end-tidal carbon dioxide is a cornerstone of modern anesthetic practice. It serves as a non-invasive, continuous surrogate for arterial partial pressure of carbon dioxide, reflecting the integration of cellular metabolism, cardiovascular delivery, and pulmonary ventilation. A sudden fall in end-tidal carbon dioxide during anesthesia often signals a critical intraoperative event, ranging from benign sampling errors to life-threatening pulmonary embolism.

In renal transplant recipients, intraoperative physiology is further complicated by fluid shifts, electrolyte derangements, and immunosuppressive therapies. Anesthetic vigilance in this population requires an understanding of both molecular physiology and clinical interpretation of monitoring changes.

This chapter expands upon a clinical scenario: a 31-year-old male undergoing renal transplantation, 2 hours into the procedure, experiencing a sudden end-tidal carbon dioxide drop from 27 millimeters of mercury to 18 millimeters of mercury, while remaining hemodynamically stable. Through this lens, we explore the molecular, physiological, and clinical mechanisms underlying end-tidal carbon dioxide changes, with an evidence-based algorithm for management.

References:

1. Miller RD, Cohen NH, Eriksson LI, Fleisher LA, Wiener-Kronish JP, Young WL. Miller’s Anesthesia. 9th edition. Philadelphia: Elsevier; 2020.
2. Barash PG, Cullen BF, Stoelting RK, Cahalan MK, Stock MC, Ortega R. Clinical Anesthesia. 9th edition. Philadelphia: Wolters Kluwer; 2021.

2. Physiology and Molecular Basis of Carbon Dioxide Transport2.1 Production of Carbon Dioxide

Carbon dioxide is the final metabolic product of aerobic metabolism. At the cellular level, carbon dioxide originates primarily in the tricarboxylic acid cycle during oxidative decarboxylation reactions (isocitrate to alpha-ketoglutarate, alpha-ketoglutarate to succinyl-CoA). Each glucose molecule metabolized via oxidative phosphorylation generates approximately six molecules of carbon dioxide.

Molecularly, the rate of carbon dioxide production is tightly coupled to adenosine triphosphate demand. Hypothermia or pharmacological metabolic suppression (for example: anesthetics, muscle relaxants) reduce enzymatic activity through the Q₁₀ effect, lowering carbon dioxide production.

2.2 Transport of Carbon Dioxide in Blood

• Bicarbonate (90 percent): Carbon dioxide diffuses into erythrocytes, where carbonic anhydrase II catalyzes hydration to carbonic acid → hydrogen ion + bicarbonate. Chloride shift maintains electroneutrality.
• Carbamino compounds (5 percent): Carbon dioxide binds terminal amine groups of hemoglobin to form carbaminohemoglobin.
• Dissolved carbon dioxide (5 percent): According to Henry’s law, proportional to arterial partial pressure of carbon dioxide.

2.3 Alveolar Exchange

Diffusion across the alveolar-capillary membrane is governed by Fick’s law, influenced by surface area, membrane thickness, diffusion constant, and partial pressure gradient. Carbon dioxide diffuses approximately 20 times faster than oxygen due to higher solubility.

2.4 End-Tidal Carbon Dioxide–Arterial Partial Pressure of Carbon Dioxide Gradient

Under normal conditions, end-tidal carbon dioxide is 2–5 millimeters of mercury lower than arterial partial pressure of carbon dioxide, due to alveolar dead space ventilation. This gradient widens with increased dead space (for example: pulmonary embolism, low perfusion states).

References:

3. West JB. Respiratory Physiology: The Essentials. 11th edition. Philadelphia: Wolters Kluwer; 2021.

4. Ward JP, Clarke R. An Introduction to Human Disease. 10th edition. Jones & Bartlett; 2019.

5. Lumb AB. Nunn’s Applied Respiratory Physiology. 9th edition. Philadelphia: Elsevier; 2021.

3. Capnography: Physics and Technology3.1 Principle of Infrared Absorption

Capnography is based on infrared absorption spectroscopy. Carbon dioxide has a characteristic absorption peak at 4.3 micrometers due to vibrational transitions of the carbon-oxygen double bond. The degree of infrared light absorbed is proportional to the concentration of carbon dioxide molecules in the gas stream.

3.2 Mainstream versus Sidestream Systems

• Mainstream: sensor placed directly in airway; immediate response, but adds dead space.
• Sidestream: gas sampled via tubing to an analyzer; more versatile but prone to leaks, condensation, and delay.

3.3 Common Artifacts

• Kinked sampling line → reduced carbon dioxide delivery to analyzer.
• Water trap condensation → absorption interference.
• Excessive fresh gas flow → dilutional effect.
• Analyzer pump malfunction → inadequate sample aspiration.

References:

6. Bhavani-Shankar K, Moseley H, Kumar AY, Delph Y. Capnometry and anaesthesia. Canadian Journal of Anaesthesia. 1992;39(6):617–32.

7. Kodali BS. Capnography: a comprehensive review. Anesthesiology Clinics. 2012;30(1):45–62.

4. Clinical Case Analysis: Sudden Fall in End-Tidal Carbon Dioxide4.1 Case Correlation

• Respiratory rate, tidal volume, minute ventilation, positive end-expiratory pressure unchanged → no ventilator-induced hyperventilation.
• End-tidal carbon dioxide waveform persists at lower amplitude → not total disconnection.
• Hemodynamics stable → rules out major embolism or cardiac arrest.

Interpretation: most consistent with technical artifact rather than physiological catastrophe.

References:

8. Eipe N, Doherty DR. A physiological approach to capnography. British Journal of Anaesthesia Education. 2010;10(5):161–7.

5. Differential Diagnosis of Sudden End-Tidal Carbon Dioxide Drop5.1 Technical Causes

• Sampling line leak or kink.
• Water condensation in trap.
• Analyzer malfunction.
• Dilution from high fresh gas flows.

5.2 Physiological Causes

• Pulmonary embolism (air or thrombus): sudden increase in dead space → decreased end-tidal carbon dioxide, often with hemodynamic collapse.
• Pneumothorax: decreased alveolar ventilation on one side, increased dead space.
• Hyperventilation: decreased arterial partial pressure of carbon dioxide → decreased end-tidal carbon dioxide.
• Metabolic suppression: decreased carbon dioxide production (hypothermia, anesthetic depression).

5.3 Prioritization

• Most likely: Technical artifact.
• Dangerous but less likely: Embolism, pneumothorax.
• Rare: Metabolic suppression.

References:

9. Bhavani-Shankar K, Kumar AY, Moseley H. Terminology and limitations of time capnography. Journal of Clinical Monitoring and Computing. 1995;11(3):175–82.

10. Wood KE. Major pulmonary embolism: pathophysiology. Chest. 2002;121(3):877–905.

6. Renal Transplant Context6.1 Fluid Balance

Large intraoperative volume shifts may alter pulmonary perfusion, influencing end-tidal carbon dioxide.

6.2 Electrolyte Abnormalities

• Hyperkalemia → membrane depolarization → impaired respiratory muscle function.
• Hypocalcemia → lower threshold potential → muscle irritability.

6.3 Immunosuppressants

• Calcineurin inhibitors impair mitochondrial oxidative phosphorylation, altering carbon dioxide production.
• Steroids increase gluconeogenesis, increasing carbon dioxide generation.

6.4 Surgical Risks

During vascular anastomosis, venous air entrainment is possible → risk of air embolism, presenting as sudden end-tidal carbon dioxide fall.

References:

11. O’Malley CM, Moriarty DC, Wong K. Anaesthesia for renal transplantation. British Journal of Anaesthesia Education. 2017;17(12):401–8.

12. Verma A, Prasad G. Anaesthesia for renal transplantation: Current perspectives. Indian Journal of Anaesthesia. 2016;60(11):757–64.

13. Naesens M, Kuypers DR, Sarwal M. Calcineurin inhibitor nephrotoxicity. Clinical Journal of the American Society of Nephrology. 2009;4(2):481–508.

7. Stepwise Management AlgorithmStep 1: Patient Check

• Oxygen saturation, chest movement, auscultation, airway pressures.
• Molecular: hemoglobin–oxygen affinity (Bohr effect) ensures rapid detection of ventilatory compromise.

Step 2: Monitor and Circuit Check

• Inspect sampling line, connectors, and water trap.
• Replace defective tubing.
• Check fresh gas flows.

Step 3: Physiological Consideration

• Hyperventilation? (check ventilator settings).
• Embolism? (sudden desaturation, hypotension).
• Hypothermia? (temperature, metabolic rate).

Step 4: Confirm with Arterial Blood Gas

• Arterial partial pressure of carbon dioxide–end-tidal carbon dioxide gap helps differentiate artifact versus true physiology.

Step 5: Management

• Artifact → replace line or trap.
• Hyperventilation → reduce minute ventilation.
• Embolism → notify surgical team, flood field, support hemodynamics, aspirate via central line if possible.

Step 6: Document and Communicate

Essential for safety and medico-legal protection.

References:

14. Hartmann T, Fiamoncini J, Grafetstätter M, Verstraeten S. Molecular basis of metabolic rate regulation. Molecular and Cellular Biochemistry. 2019;454(1–2):1–15.

15. American Society of Anesthesiologists. Standards for Basic Anesthetic Monitoring. ASA Guidelines. 2020.

8. Practical Mnemonic — C-A-M-E-L

• Check patient (clinical assessment plus oxygenation).
• Alter ventilator (minute ventilation).
• Monitor sampling line (integrity).
• Evaluate embolism or dead space.
• Log and communicate.

References:

16. Sinha PK, Singh B. Capnography in anaesthesia and intensive care. Indian Journal of Anaesthesia. 2003;47(6):437–46.

9. Conclusion

A sudden drop in end-tidal carbon dioxide during anesthesia demands immediate attention. In this case, a stable 31-year-old renal transplant recipient experiencing a fall from 27 millimeters of mercury to 18 millimeters of mercury most likely represents capnography artifact. However, the differential includes serious pathologies such as embolism and pneumothorax. Understanding the molecular physiology of carbon dioxide transport, the physics of capnography, and renal transplant-specific risks enables anesthesiologists to respond rapidly and appropriately.

References:

17. West JB, Luks AM. West’s Pulmonary Pathophysiology: The Essentials. 10th edition. Wolters Kluwer; 2021.

18. Nunn JF. Nunn’s Applied Respiratory Physiology. 9th edition. Elsevier; 2021.