|Year : 2014 | Volume
| Issue : 1 | Page : 1-4
Permissive hypercapnia: From the ICU to the operating room
Faculty of Medicine, Cairo University, Cairo, Egypt
|Date of Submission||13-Dec-2013|
|Date of Acceptance||02-Apr-2014|
|Date of Web Publication||21-Jul-2014|
MSc, 14A Hassan Mohamed, Fatma Roushdy st. Al Haram, 12554, Cairo
Source of Support: None, Conflict of Interest: None
Although the effect of permissive hypercapnia on hemodynamics and right ventricular function was previously reported in patients with acute respiratory distress syndrome, the effects of acute controlled hypercapnia on right ventricular function during one-lung ventilation have not yet been investigated systematically. Experimental evidence is conflicting concerning the pulmonary vasodilatory or vasoconstrictive effect of hypercapnic acidosis. The final effect of hypercapnic acidosis on physiological functions depends on the level of hypercapnia and the context of the individual (healthy vs. diseased).
Keywords: One-lung ventilation, permissive hypercapnia, right ventricular function
|How to cite this article:|
Wagih M. Permissive hypercapnia: From the ICU to the operating room. Egypt J Cardiothorac Anesth 2014;8:1-4
| Introduction|| |
One-lung ventilation (OLV) in patients undergoing pulmonary resection is challenging and fraught of many complications. One of these complications is increased airway pressure of the dependent lung with potential risk for barotrauma .
During OLV, tidal volume (Vt) is frequently maintained at the same level as during two-lung ventilation without positive end-expiratory pressure (PEEP), targeting normalization of CO 2 ,. This maintenance corresponds to high-volume ventilation with potentially deleterious effects, even for a period of less than 90 min ,. Normalizing CO 2 at the expense of inducing undue lung stretch may not be appropriate.
In mechanically ventilated ICU patients, reduced Vt with an associated increased CO 2 (permissive hypercapnia) has become an accepted practice ,. Recently, Michelet et al.  demonstrated that the protective ventilatory strategy based on the reduction of Vt is beneficial during OLV.
The increased hypoxic pulmonary vasoconstriction (HPV) during hypercapnic acidosis (HCA) is beneficial to lung gas exchange by improving ventilation-perfusion matching and preserving the capillary barrier function. These effects seem to be linked to the NO-mediated pathways .
Although the effect of permissive hypercapnia on hemodynamics and right ventricular (RV) function was previously reported in patients with acute respiratory distress syndrome (ARDS) , the effects of acute controlled hypercapnia on RV function during OLV have not yet been investigated systematically.
Potentially harmful consequences of permissive hypercapnia include pulmonary vasoconstriction and pulmonary hypertension, proarrhythmic effects of increased discharge of the sympathetic nervous system, and cerebral vasodilation yielding increased intracranial pressure. However, experimental data have suggested that permissive hypercapnia is not only safe, but also potentially beneficial. Nonetheless, permissive hypercapnia should probably be used with caution in patients with heart disease and is relatively contraindicated in those with elevated intracranial pressure .
HCA has a myriad of effects on many physiological processes. The recognition of these effects is important as it will affect the decision whether or not to allow the development of HCA in a specific patient. As outlined below, the final effect of HCA on physiological functions depends on the level of hypercapnia, the context of the individual (healthy vs. diseased), and many other factors .
| Hypercapnic acidosis and oxygenation|| |
The beneficial effects of HCA in increasing arterial and tissue oxygenation is evident from multiple in-vivo studies , and have been demonstrated in healthy humans as well . HCA can improve tissue oxygenation by several mechanisms. First, a rightward shift of the oxyhemoglobin dissociation curve during acute respiratory acidosis decreases the affinity of hemoglobin for oxygen and facilitates oxygen release to the tissues (the Bohr effect) . Second, HCA causes vasodilatation in microvessels, promoting oxygen delivery and tissue perfusion. However, high concentrations of PaCO 2 (>100 mmHg) will surpass the beneficial vasodilatory effects of HCA and result in vasoconstriction . Third, HCA improves ventilation-perfusion (V/Q) matching by potentiating HPV ,. However, HPV could be partly blunted by inhalational anesthetics, but there is no clear evidence to support that inhalational agents could attenuate or abolish the effect of HCA on HPV. Fourth, as cardiac output is one of the major determinants of peripheral oxygen delivery, one can expect that a CO 2 -mediated increase in cardiac output augments peripheral oxygen delivery. However, an increase in cardiac output results in an increase in mixed venous oxygen tension, which may lead to an increase in pulmonary shunting due to attenuation of HPV ,.
Hypercapnic acidosis and pulmonary compliance
It has been demonstrated in experimental studies that pulmonary compliance is improved by HCA. This may be explained by the pH-mediated effect of HCA in improving surfactant secretion and its surface tension-lowering properties ,.
Hypercapnic acidosis and pulmonary vascular tone
Increases in pulmonary vascular tone may have particularly unfavorable consequences in patients with pulmonary hypertension. Experimental evidence is conflicting concerning the pulmonary vasodilatory or vasoconstrictive effect of HCA ,,. These apparent opposing effects may be attributable to the presence or absence of pH buffer resulting in pulmonary vasodilatation or vasoconstriction, respectively ,,.
However, clinical studies demonstrate that HCA causes an increase in mean pulmonary arterial pressure in ARDS ,. Recently, Mekontso et al.  showed a lower RV stroke index in patients with severe ARDS who were ventilated with higher PEEP (10-11 mmHg) at a constant plateau pressure that subsequently led to HCA (pH 7.17-7.20, PaCO 2 70-75 mmHg). An increase in pulmonary vascular resistance was postulated, but no objective measurements were performed. Multivariate analysis demonstrated that pH, per se, and not CO 2 or PEEP, was responsible for the impaired RV function . Therefore, caution is warranted with the use of 'permissive' or 'therapeutic' HCA in patients with pulmonary hypertension and depressed RV function.
| Hypercapnic acidosis and cardiovascular system|| |
Effects on cardiac output
HCA has a direct suppressive effect on cardiac contractility, but it can lead to a net increase in cardiac output by several mechanisms, as has been demonstrated in both animal and human studies ,,,,,. First, sympathetically mediated release of catecholamines due to neuroadrenal stimulation results in an increase in end-systolic volume and venous return ,. In addition to an increase in heart rate, HCA induces ATP-sensitive K + channel-mediated vasodilation, as has been demonstrated for the brain vasculature and coronary vessels ,, which could decrease left ventricular afterload. An increase in 10-12 mmHg in PaCO 2 increases the cardiac index by 14% in the critically ill and healthy mechanically ventilated patients ,. In the clinical setting, however, care should be taken with patients exhibiting depressed myocardial function.
Effects on the myocardium
Acidosis has protective effects against myocardial ischemia-reperfusion injury ,. Hydrogen ions inhibit Ca 2+ influx into the myocardial fiber, which decreases myocardial contractility and oxygen demand, leading to less tissue injury during myocardial ischemia ,. Furthermore, hypercapnia causes coronary vasodilatation, which may be of further benefit during the period of reperfusion . These protective effects of hypercapnia can be of pivotal importance in the treatment of patients undergoing coronary artery bypass grafting with extracorporeal circulation and subsequently experiencing myocardial suppression.
Perhaps, the most comprehensive study on the effects of hypercapnia on pulmonary circulation and the heart was conducted by Kiely et al.  in healthy young volunteers, using a Doppler ultrasound control method. The volunteers were tested before and after inhaling a CO 2 -rich mixture with the aim of achieving hypercapnia of 55-60 mmHg with the measurement of numerous useful parameters to assess the response of pulmonary circulation, peripheral circulation, and the heart. In the systemic circulation, an increase in CO, SV, HR, SBP, DBP, and MAP has been observed with a slight and insignificant reduction in SVR. Changes of this kind were already observed 50 years ago by Price  and 35 years ago by Cullen and Enger . However, whereas previous experiments on isolated hearts demonstrated a depressant effect for hypercapnia , in this study no such effect was found. In fact, increased aortic flow and peak flow did not change with hypercapnia, meaning that this neither reduced nor increased myocardial contractility.
The direct effect of HCA on the heart and vascular smooth muscle is to reduce contractility. However, these direct effects are opposed by a neurohumeral effect, thus resulting in an increase in sympathomimetic output. This leads to an increase in HR, systemic vasodilatation, and decrease in left ventricular afterload, which results in an increase in CO .
Hypercapnia targeting CO 2 50-70 mmHg was associated with increased cardiac output, central venous O 2 , and arterial O 2 tension in patients undergoing video-assisted thoracoscopic patent ductus arteriosus closure using OLV without any deleterious cardiopulmonary effects .
| Conclusion|| |
Permissive hypercapnia should be a routine component of OLV management. With a reasonable cardiovascular reserve, and in particular RV function, PaCO 2 levels up to 60-70 mmHg are likely to be well tolerated in the short-term and are clearly beneficial in terms of lung injury avoidance and attenuation. However, more research is needed to investigate the effect of hypercapnia on the right ventricle. The final effect of HCA on physiological functions depends on the level of hypercapnia and the context of the individual.
| Acknowledgements|| |
Conflicts of interest
There are no conflicts of interest.
| References|| |
|1.||Garnmon RB, Shin MS, Buchalter SE. Pulmonary barotrauma in mechanical ventilation. Patterns and risk factors Chest 1992; 102:568-572. |
|2.|| Benumof J. Conventional and differential lung management of one-lung ventilation. In: Anesthesia for thoracic surgery. 2nd ed. Philadelphia: Saunders; 1994. 413-424. |
|3.|| Brodsky J, Fitzmaurice B. Modern anesthetic techniques for thoracic operations. World J Surg 2001; 25:162-166. |
|4.|| Gama de Abreu M, Heintz M, Heller A, Széchényi R, Albrecht DM, Koch T. One-lung ventilation with high tidal volumes and zero positive end-expiratory pressure is injurious in the isolated rabbit lung model. Anesth Analg 2003; 96:220-228. |
|5.|| Tandon S, Batchelor A, Bullock R, Gascoigne A, Griffin M, Hayes N et al. Peri-operative risk factors for acute lung injury after elective oesophagectomy. Br J Anaesth 2001; 86:633-638. |
|6.|| ARDS Network. Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome. N Engl J Med 2000; 342:1301-1308. |
|7.|| Amato MB, Barbas CS, Medeiros DM, Magaldi RB, Schettino GP, Lorenzi-Filho G et al. Effect of a protective-ventilation strategy on mortality in the acute respiratory distress syndrome. N Engl J Med 1998; 338:347-354. |
|8.|| Michelet P, D′Jo XB, Roch A, Doddoli C, Marin V, Papazian L et al. Protective ventilation influences systemic inflammation after esophagectomy: A randomized controlled study. Anesthesiology 2006; 105:911-919. |
|9.|| Ketabchi F, Egemnazarov B, Schermuly RT, Ghofrani HA, Seeger W, Grimminger F et al. Effects of hypercapnia with and without acidosis on hypoxic pulmonary vasoconstriction. Am J Physiol Lung Cell Mol Physiol 2009; 297:977-983. |
|10.||1Mekontso Dessap A, Charron C, Devaquet J, Aboab J, Jardin F, Brochard L et al. Impact of acute hypercapnia and augmented positive end-expiratory pressure on right ventricle function in severe acute respiratory distress syndrome. Intensive Care Med 2009; 35:1850-1858. |
|11.||1Kavanagh BP, Laffey JG. Hypercapnia: permissive and therapeutic. Minerva Anestesiol 2006; 72:567-576. |
|12.||1MM Ijland, LM Heunks, JG Van der Hoeven. Bench-to-bedside review: hypercapnic acidosis in lung injury - fro ′permissive′ to ′therapeutic′. Crit Care 2010; 14:237. |
|13.||1Laffey JG, Engelberts D, Duggan M, Veldhuizen R, Lewis JF, Kavanagh BP. Carbon dioxide attenuates pulmonary impairment resulting from hyperventilation. Crit Care Med 2003; 31:2634-2640. |
|14.||1Swenson ER, Robertson HT, Hlastala MP. Effects of inspired carbon dioxide on ventilation-perfusion matching in normoxia, hypoxia, and hyperoxia. Am J Respir Crit Care Med 1994; 149:1563-1569. |
|15.||1Akca O, Doufas AG, Morioka N, Iscoe S, Fisher J, Sessler DI. Hypercapnia improves tissue oxygenation. Anesthesiology 2002; 97:801-806. |
|16.||1Turek Z, Kreuzer F. Effect of shifts of the O 2 dissociation curve upon alveolar-arterial O 2 gradients in computer models of the lung with ventilation-perfusion mismatching. Respir Physiol 1981; 45:133-139. |
|17.||1Komori M, Takada K, Tomizawa Y, Nishiyama K, Kawamata M, Ozaki M. Permissive range of hypercapnia for improved peripheral microcirculation and cardiac output in rabbits. Crit Care Med 2007; 35:2171-2175. |
|18.||1Wang Z, Su F, Bruhn A, Yang X, Vincent JL. Acute hypercapnia improves indices of tissue oxygenation more than dobutamine in septic shock. Am J Respir Crit Care Med 2008; 177:178-183. |
|19.||1Pfeiffer B, Hachenberg T, Wendt M. Mechanical ventilation with permissive hypercapnia increases intrapulmonary shunt in septic and nonseptic patients with acute respiratory distress syndrome. Crit Care Med 2002; 30:285-289. |
|20.||2Hickling KG, Joyce C. Permissive hypercapnia in ARDS and its effect on tissue oxygenation. Acta Anaesthesiol Scand Suppl 1995; 107:201-208. |
|21.||2Shepard JWJr, Dolan GF, Yu SY. Factors regulating lamellar body volume density of type II pneumocytes in excised dog lungs. J Appl Physiol 1982; 53:555-562. |
|22.||2Wildeboer-Venema F. Influence of nitrogen, oxygen, air and alveolar gas upon surface tension of lung surfactant. Respir Physiol 1984; 58:1-14. |
|23.||2Laffey JG, Jankov RP, Engelberts D, Tanswell AK, Post M, Lindsay T et al. Effects of therapeutic hypercapnia on mesenteric ischemia-reperfusion injury. Am J Respir Crit Care Med 2003; 168:1383-1390. |
|24.||2Laffey JG, Engelberts D, Kavanagh BP. Buffering hypercapnic acidosis worsens acute lung injury. Am J Respir Crit Care Med 2000; 161:141-146. |
|25.||2Ooi H, Cadogan E, Sweeney M, Howell K, O′Regan RG, McLoughlin P. Chronic hypercapnia inhibits hypoxic pulmonary vascular remodeling. Am J Physiol Heart Circ Physiol 2000; 278:H331-H338. |
|26.||2Viles PH, Shepherd JT. Evidence for a dilator action of carbon dioxide on the pulmonary vessels of the cat. Circ Res 1968; 22:325-332. |
|27.||2Thorens JB, Jolliet P, Ritz M, Chevrolet JC. Effects of rapid permissive hypercapnia on hemodynamics, gas exchange, and oxygen transport and consumption during mechanical ventilation for the acute respiratory distress syndrome. Intensive Care Med 1996; 22:182-191. |
|28.||2Weber T, Tschernich H, Sitzwohl C, Ullrich R, Germann P, Zimpfer M et al. Tromethamine buffer modifies the depressant effect of permissive hypercapnia on myocardial contractility in patients with acute respiratory distress syndrome. Am J Respir Crit Care Med 2000; 162:1361-1365. |
|29.||2Mas A, Saura P, Joseph D, Blanch L, Baigorri F, Artigas A et al. Effect of acute moderate changes in PaCO 2 on global hemodynamics and gastric perfusion. Crit Care Med 2000; 28:360-365. |
|30.||3Brofman JD, Leff AR, Munoz NM, Kirchhoff C, White SR. Sympathetic secretory response to hypercapnic acidosis in swine. J Appl Physiol 1990; 69:710-717. |
|31.||3Walley KR, Lewis TH, Wood LD Acute respiratory acidosis decreases left ventricular contractility but increases cardiac output in dogs. Circ Res 1990; 67:628-635. |
|32.||3Nakahata K, Kinoshita H, Hirano Y, Kimoto Y, Iranami H, Hatano Y. Mild hypercapnia induces vasodilation via adenosine triphosphate-sensitive K+ channels in parenchymal microvessels of the rat cerebral cortex. Anesthesiology 2003; 99:1333-1339. |
|33.||3Phillis JW, Song D, O′Regan MH. Mechanisms involved in coronary artery dilatation during respiratory acidosis in the isolated perfused rat heart. Basic Res Cardiol 2000; 95:93-97. |
|34.||3Kitakaze M, Takashima S, Funaya H, Minamino T, Node K, Shinozaki Y et al. Temporary acidosis during reperfusion limits myocardial infarct size in dogs. Am J Physiol 1997; 272:H2071-H2078. |
|35.||3Kitakaze M, Weisfeldt ML, Marban E. Acidosis during early reperfusion prevents myocardial stunning in perfused ferret hearts. J Clin Invest 1988; 82:920-927. |
|36.||3Orchard CH, Kentish JC. Effects of changes of pH on the contractile function of cardiac muscle. Am J Physiol 1990; 258:C967-C981. |
|37.||3Nomura F, Aoki M, Forbess JM, Mayer JE Jr. Effects of hypercarbic acidotic reperfusion on recovery of myocardial function after cardioplegic ischemia in neonatal lambs. Circulation 1994; 90:II321-II327. |
|38.||3David G. Kiely, Robert I. Cargill, Brian J. Lipworth. Effects of Hypercapnia on Hemodynamic, Inotropic, Lusitropic, and Electrophysiologic Indices in Humans. Chest 1996; 109:1215-1221. |
|39.||3Price HL. Effects of carbon dioxide on the cardiovascular system. Anesthesiology 1960; 21:652-653. |
|40.||4Cullen DJ, Enger EI. Cardiovascular effects of carbon dioxide in man. Anesthesiology 1974; 41:345-349. |
|41.||4Vaughan Williams EM. Individual effects of CO 2 , bicarbonate and pH on the electrical and mechanical activity of isolated rabbit auricles. J Physiol 1955; 129:90-110. |
|42.||4Mukhtar AM, Obayah GM, El masry A, Dessouky NM. The therapeutic potential of intraoperative hypercapnia during video-assisted thoracoscopy in pediatric patients. Anesth Analg 2008; 106:84-88. |