CO2 is good for you!
Myron Yaster MD and Jeffrey R. Gross MD
When I was about 4 months into my anesthesia residency at the University of Pennsylvania and on my VA rotation, the anesthesia machines were equipped with a copper kettle, a rudimentary ECG monitor, a bellows ventilator, and not much else (pulse oximetry, and capnography were not yet invented). It did have a rebreather valve that when unscrewed would remove the CO2 absorber from the circuit and allow for rebreathing of CO2 (figure, courtesy of Dr. Gross). Why this valve? As CO2 rose, patients would hyperventilate and exhale and remove the residual anesthetic agent (halothane and N20) more rapidly and hasten wakeup. During a very memorable case, my attending, Ted Smith, while talking to me unscrewed this valve and left the room to see how I would react. Over the next couple of minutes, the patient’s HR and BP rose and the patient became extremely diaphoretic. He also felt warm! I got an arterial blood gas which revealed a PaCO2 of 90 and a pH of 7.1! Ah ha Malignant Hyperthermia! I informed the surgeon that the patient had MH and called for help. I turned off the halothane, a rubber life raft was brought into the room and filled with ice and saline, the surgeon began to emergently close, when my attending arrived and turned back the switch and with the CO2 absorber now in place everything returned to normal. (Ted had left the room and forgot that he removed the CO2 absorber from the circuit). Many lessons learned!
Today’s PAAD reviews an editorial and original article about the effects of CO2 on the MAC of sevoflurane in adult patients. It’s worth your while to read it and you can even obtain CME from IARS for doing it!
Editorial
Derek J Sakata. Carbon Dioxide as the Other Therapeutic Carrier Gas? Anesth Analg. 2022 Jul 1;135(1):60-61. PMID: 35709445
Original article
Zhijie Wu, Junjie Yu, Tianhua Zhang, Hongying Tan, Huiting Li 1, Lan Xie, Wenqian Lin, Danping Shen, Longhui Cao. Effects of Etco2 on the Minimum Alveolar Concentration of Sevoflurane that Blunts the Adrenergic Response to Surgical Incision: A Prospective, Randomized, Double-Blinded Trial. Anesth Analg. 2022 Jul 1;135(1):62-70. PMID: 34744156 1
If you walk into almost any OR in the U.S., the endtidal CO2 in a mechanically ventilated patient will invariably be between 25-34. Rarely is the CO2 allowed to be “normal” or in the high 40s or 50s…except perhaps in spontaneously breathing patients (where the endtidal CO2 usually is around 52 mm Hg at MAC). And even in spontaneously breathing patients, they are often switched to mechanical ventilation to get the CO2 down (and for those of you teach, this is accompanied by “what were you thinking…you must’ve been recently working with Yaster or Gross”?). To be honest, we’ve never understood this or why anyone would want to produce a respiratory alkalosis in any patient other than those with high ICP or pulmonary artery hypertension.
There are many benefits to hypercarbia in the OR and the production of respiratory acidosis. “With few exceptions, alkalosis is never normal. Alkalosis shifts the oxygen dissociation curve to the left, preventing the unloading of oxygen to the tissues, decreases blood flow to the brain and heart, and depresses minute ventilation. Also, mechanical hyperventilation decreases venous return by increasing mean intrathoracic pressure. On the other hand, acidosis is very common and occurs every time one exercises. It produces many salutary effects, including increased cardiac output, blood pressure, and heart rate, as well as increased blood flow to organs that are vulnerable to ischemia, such as the brain, heart, and kidneys. Perhaps most importantly to the anesthesiologist, acidosis causes a rightward shift in the oxygen dissociation curve, which improves oxygen unloading to all of the tissues in the body, and because hydrogen ion is the primary driver of ventilation at the chemoreceptor in the brainstem, it is the primary driver of ventilation”.2 Based on today’s article by Wu et al,1 we can add a reduction in sevoflurane’s MAC to the list of the benefits of hypercarbia.
Wu et al. used a classic up down method to determine the MAC of sevoflurane in adults undergoing gastric cancer surgery. Rather than using the classic movement to surgical stimulation to determine MAC, the authors used hemodynamic responses to surgical stimulus or the amount of sevoflurane that blunts the adrenergic response to surgical incision in 50% of patients (MAC-BAR). Patients were divided into 3 groups, low endtidal CO2 25-30 mmHg, normal endtidal CO2 30-40 mmHg, and high endtidal CO2 40-45 mmHg (figure). The authors found that higher CO2 levels significantly decreased sevoflurane’s MAC-BAR.
Why did hypercarbia reduce MAC? To be honest, the better question is why didn’t we think of this before and do this study ourselves? “Previous studies have shown that hypercapnia raises the pain threshold, which may be related to the effects of CO2 on neuronal excitability at various levels of the nervous system”.1,3 “Fukuda et al reported that moderate hypercapnia induced anesthetic effects, which were reversed by naloxone pretreatment”.1,4 Finally, “It has also been established that CO2-induced analgesia occurs because of central stress-related mechanisms, which are linked to the release of adrenocorticotropin hormone (ACTH)”.1,5 Perhaps the simplest explanation is that hypercarbia by increasing cerebral blood flow delivers more anesthetic to the brain at induction and removes more anesthetic on emergence.6 Further, this principle enables devices such as the ANEclear to speed emergence from anesthesia by essentially doing what the CO2 rebreathing valve did in the past. It allows rebreathing of CO2 to drive up minute ventilation plus it also includes an absorber to prevent patients from rebreathing their own exhaled volatile anesthetic agents and dumping it into the atmosphere (https://www.anecare.com).7 (As an aside: have any of you used this device?)
One final thought. In this study, endtidal CO2 routinely underestimated arterial CO2 by about 30%. Thus, the endtidal measurements were about 5 mm Hg lower than measured arterial blood gas measurements. Thus, the arterial CO2 levels averaged around of 50 =/- 3 mm Hg in the hypercarbia group not the 45 mm Hg measured via capnography that the investigators targeted.
References
Wu Z, Yu J, Zhang T, Tan H, Li H, Xie L, Lin W, Shen D, Cao L: Effects of Etco2 on the Minimum Alveolar Concentration of Sevoflurane that Blunts the Adrenergic Response to Surgical Incision: A Prospective, Randomized, Double-Blinded Trial. Anesth Analg 2022; 135: 62-70
Yaster M, Gross JB: CO2 is Good for You! Anesth Analg 2021; 132: e13
Gamble GD, Milne RJ: Hypercapnia depresses nociception: endogenous opioids implicated. Brain Res 1990; 514: 198-205
Fukuda T, Hisano S, Toyooka H: Moderate hypercapnia-induced anesthetic effects and endogenous opioids. Neurosci Lett 2006; 403: 20-3
Grönroos M, Pertovaara A: A selective suppression of human pain sensitivity by carbon dioxide: central mechanisms implicated. Eur J Appl Physiol Occup Physiol 1994; 68: 74-9
Sakata DJ: Carbon Dioxide as the Other Therapeutic Carrier Gas? Anesth Analg 2022; 135: 60-61
Katznelson R, Djaiani G, Naughton F, Wasowicz M, Ragoonanan T, Duffin J, Fedorko L, Murphy J, Fisher JA: Post-operative hypercapnia-induced hyperpnoea accelerates recovery from sevoflurane anaesthesia: a prospective randomised controlled trial. Acta Anaesthesiol Scand 2013; 57: 623-30