Faster Recovery from Anesthesia with CO2 Therapy
All general anesthetics are toxic agents in varying degrees and prone to produce undesirable after-effects on the patient. It is, therefore, advantageous to accelerate their elimination the moment their work is completed.
Controlled hyperventilation, known in medical terms as isocapnic hyperpnea, is gaining renewed interest as a powerful tool in clinical practice. Unlike normal hyperventilation, which causes a drop in carbon dioxide (CO₂) and can lead to dizziness or fainting, isocapnic hyperventilation maintains stable CO₂ levels by adding CO₂ to the inhaled air. This technique, now referred to as CO₂ therapy, is proving to be a game-changer in several clinical scenarios—especially in post-anesthesia recovery.
The Challenge: Slow Recovery After Inhalation Anesthesia
Inhalation anesthetics like sevoflurane are widely used in surgeries for their efficacy and rapid onset. However, their slow elimination from the body can prolong the time to extubation, delay eye-opening, and extend the patient's stay in post-anesthesia care units (PACUs).
Hyperventilation accelerates the washout of these gases from the lungs, but doing so without CO₂ supplementation results in hypocapnia, leading to cerebral vasoconstriction and possible postoperative complications like apnea and delayed cognition.
CO₂ Therapy to the Rescue
CO₂ therapy solves this issue by maintaining normal CO₂ levels during controlled hyperventilation. The lungs are essentially recruited as a powerful organ for blood filtration, aiding in the rapid elimination of inhaled anesthetics.
In a seminal clinical pilot trial published in Acta Anaesthesiologica Scandinavica [ref5], researchers used a standardized protocol that involved:
- Doubling baseline mechanical ventilation
- Adding CO₂ directly into the inspiratory limb of the breathing circuit via a mixing box
- Using a nomogram to calculate CO₂ flow based on patient gender and body weight
The result? Patients woke up and were extubated more than twice as fast as in traditional recovery. Cognitive function returned to baseline in the majority of patients within an hour, and there were no adverse effects.
Backed by Bench and Clinical Studies
Bench models have also confirmed the efficacy of this technique. In a study using a mechanical lung model, Hallén and colleagues [ref4] demonstrated that CO₂ levels could be precisely controlled during hyperventilation using standard anesthesia circuits. This ensured that the increased ventilation did not trigger hypocapnia and significantly enhanced the elimination rate of residual anesthetic gases.
Historical data supports this as well. In his 1924 lecture Carbon Dioxide in Anaesthesia, S.R. Wilson of Manchester University [ref3] described how carbon dioxide acted as a "respiratory hormone," maintaining automatic breathing even when other stimuli were suppressed by anesthetics. Wilson emphasized the benefits of CO₂ for faster recovery, fewer post-op complications, and improved hemodynamic stability.
Real-World Clinical Benefits
- Shorter wake-up time: Time to eye-opening and extubation is significantly reduced.
- Improved cognitive recovery: Post-operative cognition returns to baseline faster.
- Reduced PACU time: Patients can be discharged from recovery units earlier.
- Better respiratory stability: Avoids the risk of apnea associated with traditional hyperventilation.
Looking Ahead
Although CO₂ therapy is not yet standard in every hospital, mounting evidence suggests it should be. It represents a practical, cost-effective way to enhance patient safety and optimize recovery times after surgery. With further adoption, this simple yet powerful intervention could redefine the protocols for post-anesthesia care.
In the world of modern medicine, sometimes the most effective innovations are those that let the body do what it does best—only better. CO₂ therapy is exactly that kind of innovation.
Scientific References
Title: Isocapnic hyperventilation provides early extubation after head and neck surgery: A prospective randomized trial.
Authors: Hallén K, Jildenstål P, Stenqvist O, Oras J, Ricksten SE, Lindgren S.
Journal: Acta Anaesthesiol Scand. 2018 Sep;62(8):1064-1071. doi: 10.1111/aas.13133. Epub 2018 Apr 19. PMID: 29671866.
Link to PubMed: Isocapnic hyperventilation provides early extubation after head and neck surgery: A prospective randomized trial. 
Abstract: Background: Isocapnic hyperventilation (IHV) shortens recovery time after inhalation anaesthesia by increasing ventilation while maintaining a normal airway carbon dioxide (CO2)-level. One way of performing IHV is to infuse CO2 to the inspiratory limb of a breathing circuit during mechanical hyperventilation (HV). In a prospective randomized study, we compared this IHV technique to a standard emergence procedure (control).
Methods: Thirty-one adult ASA I-III patients undergoing long-duration (>3 hours) sevoflurane anaesthesia for major head and neck surgery were included and randomized to IHV-treatment (n = 16) or control (n = 15). IHV was performed at minute ventilation 13.6 ± 4.3 L/min and CO2 delivery, dosed according to a nomogram tested in a pilot study. Time to extubation and eye-opening was recorded. Inspired (FICO2) and expired (FETCO2) CO2 and arterial CO2 levels (PaCO2) were monitored. Cognition was tested preoperatively and at 20, 40 and 60 minutes after surgery.
Results: Time from turning off the vapourizer to extubation was 13.7 ± 2.5 minutes in the IHV group and 27.4 ± 6.5 minutes in controls (P < .001). Two minutes after extubation, PaCO2 was 6.2 ± 0.5 and 6.2 ± 0.6 kPa in the IHV and control group respectively. In 69% (IHV) vs 53% (controls), post-operative cognition returned to pre-operative values within 40 minutes after surgery (NS). Incidences of pain and nausea/vomiting did not differ between groups.
Conclusions: In this randomized trial comparing an IHV method with a standard weaning procedure, time to extubation was reduced with 50% in the IHV group. The described IHV method can be used to decrease emergence time from inhalation anaesthesia.
Title: Isocapnic hyperventilation shortens washout time for sevoflurane - an experimental in vivo study
Authors: Hallén K, Stenqvist O, Ricksten SE, Lindgren S.
Journal: Acta Anaesthesiol Scand. 2016 Oct;60(9):1261-9. doi: 10.1111/aas.12761. Epub 2016 Jul 10. PMID: 27396945.
Link to PubMed: Isocapnic hyperventilation shortens washout time for sevoflurane - an experimental in vivo study
Abstract: Background: Isocapnic hyperventilation (IHV) is a method that fastens weaning from inhalation anaesthesia by increasing airway concentration of carbon dioxide (CO2 ) during hyperventilation (HV). In an animal model, we evaluated a technique of adding CO2 directly to the breathing circuit of a standard anaesthesia apparatus.
Methods: Eight anaesthetised pigs weighing 28 ± 2 kg were intubated and mechanically ventilated. From a baseline ventilation of 5 l/min, HV was achieved by doubling minute volume and fresh gas flow. Respiratory rate was increased from 15 to 22/min. The CO2 absorber was disconnected and CO2 was delivered (DCO2 ) to the inspiratory limb of a standard breathing circuit via a mixing box. Time required to decrease end-tidal sevoflurane concentration from 2.7% to 0.2% was defined as washout time. Respiration and haemodynamics were monitored by blood gas analysis, spirometry, electric impedance tomography and pulse contour analysis.
Results: A DCO2 of 261 ± 19 ml/min was necessary to achieve isocapnia during HV. The corresponding FICO2 -level remained stable at 3.1 ± 0.3%. During IHV, washout of sevoflurane was three times faster, 433 ± 135 s vs. 1387 ± 204 s (P < 0.001). Arterial CO2 tension and end-tidal CO2 , was 5.2 ± 0.4 kPa and 5.6 ± 0.4%, respectively, before IHV and 5.1 ± 0.3 kPa and 5.7 ± 0.3%, respectively, during IHV.
Conclusions: In this experimental in vivo model of isocapnic hyperventilation, the washout time of sevoflurane anaesthesia was one-third compared to normal ventilation. The method for isocapnic hyperventilation described can potentially be transferred to a clinical setting with the intention to decrease emergence time from inhalation anaesthesia.
Title: Carbon Dioixde in Anaesthesia
Authors: Wilson S.R.
Journal: BJA: British Journal of Anaesthesia, Volume 3, Issue 3, January 1926, Pages 112–118, https://doi.org/10.1093/bja/3.3.112
Link to full text: Carbon Dioixde in Anaesthesia 
Abstract: All general anaesthetics are toxic agents in varying degrees and prone to produce undesirable after-effects on the patient. It is therefore advantageous to effect their elimination the moment their work is completed. Henderson and Haggard have investigated the rate of excretion of ether after general anaesthesia and provided us with accurate data on this subject. They found that half the total ether in the body was eliminated in the first half hour after the administration is stopped. Half the remainder is excreted during the next one to two hours, but complete elimination does not occur until one to two days. If it is possible to accelerate this process undesirable after-effects can be greatly reduced or completely avoided.
Now, if 5–6 per cent CO₂ be added to the oxygen pulmonary ventilation is increased two, three or four times. The writer has tested these experimental observations in actual clinical practice during the last two years with most gratifying results, both to himself and the patients concerned.
Title: A simple method for isocapnic hyperventilation evaluated in a lung model
Authors: Hallén K, Stenqvist O, Ricksten SE, Lindgren S.
Journal: Acta Anaesthesiol Scand. 2016 May;60(5):597-606. doi: 10.1111/aas.12674. Epub 2015 Dec 21. PMID: 26688296.
Link to PubMed: A simple method for isocapnic hyperventilation evaluated in a lung model
Abstract: Background: Isocapnic hyperventilation (IHV) has the potential to increase the elimination rate of anaesthetic gases and has been shown to shorten time to wake-up and post-operative recovery time after inhalation anaesthesia. In this bench test, we describe a technique to achieve isocapnia during hyperventilation (HV) by adding carbon dioxide (CO2) directly to the breathing circuit of a standard anaesthesia apparatus with standard monitoring equipment.
Methods: Into a mechanical lung model, carbon dioxide was added to simulate a CO2 production (V(CO2)) of 175, 200 and 225 ml/min. Dead space (V(D)) volume could be set at 44, 92 and 134 ml. From baseline ventilation (BLV), HV was achieved by doubling the minute ventilation and fresh gas flow for each level of V(CO2), and dead space. During HV, CO2 was delivered (D(CO2)) by a precision flow meter via a mixing box to the inspiratory limb of the anaesthesia circuit to achieve isocapnia.
Results: During HV, the alveolar ventilation increased by 113 ± 6%. Tidal volume increased by 20 ± 0.1% during IHV irrespective of V(D) and V(CO2) level. D(CO2) varied between 147 ± 8 and 325 ± 13 ml/min. Low V(CO2) and large V(D) demanded a greater D(CO2) administration to achieve isocapnia. The FICO2 level during IHV varied between 2.3% and 3.3%.
Conclusion: It is possible to maintain isocapnia during HV by delivering carbon dioxide through a standard anaesthesia circuit equipped with modern monitoring capacities. From alveolar ventilation, CO2 production and dead space, the amount of carbon dioxide that is needed to achieve IHV can be estimated.
Title: Evaluation of a method for isocapnic hyperventilation: a clinical pilot trial
Authors: Hallén K, Jildenstål P, Stenqvist O, Ricksten SE, Lindgren S.
Journal: Acta Anaesthesiol Scand. 2018 Feb;62(2):186-195. doi: 10.1111/aas.13008. Epub 2017 Oct 16. PMID: 29034967.
Link to PubMed: Evaluation of a method for isocapnic hyperventilation: a clinical pilot trial
Abstract: Background: Isocapnic hyperventilation (IHV) is a method that shortens time to extubation after inhalation anaesthesia using hyperventilation (HV) without lowering airway CO2 . In a clinical trial on patients undergoing long-duration sevoflurane anaesthesia for major ear-nose-throat (ENT) surgery, we evaluated the utility of a technique for CO2 delivery (DCO2 ) to the inspiratory limb of a closed breathing circuit, during HV, to achieve isocapnia.
Methods: Fifteen adult ASA 1-3 patients were included. After end of surgery, mechanical HV was started by doubling baseline minute ventilation. Simultaneously, CO2 was delivered and dosed using a nomogram developed in a previous experimental study. Time to extubation and eye opening was recorded. Inspired (FICO2 ) and expired (FETCO2 ) CO2 and arterial CO2 levels were monitored during IHV. Cognition was tested pre-operatively and at 20, 40 and 60 min after surgery.
Results: A DCO2 of 285 ± 45 ml/min provided stable isocapnia during HV (13.5 ± 4.1 l/min). The corresponding FICO2 level was 3.0 ± 0.3%. Time from turning off the vaporizer (1.3 ± 0.1 MACage) to extubation (0.2 ± 0.1 MACage) was 11.3 ± 1.8 min after 342 ± 131 min of anaesthesia. PaCO2 and FETCO2 remained at normal levels during and after IHV. In 85% of the patients, post-operative cognition returned to pre-operative values within 60 min.
Conclusions: In this cohort of patients, a DCO2 nomogram for IHV was validated. The patients were safely extubated shortly after discontinuing long-term sevoflurane anaesthesia. Perioperatively, there were no adverse effects on arterial blood gases or post-operative cognition. This technique for IHV can potentially be used to decrease emergence time from inhalation anaesthesia.
