Asian Cardiovasc Thorac Ann 2007;15:303-306
© 2007 Asia Publishing EXchange Ltd
Adjusting Oxygen Fraction to Avoid Hyperoxemia During Cardiopulmonary Bypass
Fevzi Toraman, MD,
Serdar Evrenkaya, MD,
Sahin Senay, MD1,
Hasan Karabulut, MD,
Cem Alhan, MD
Department of Cardiovascular Surgery, Acibadem Kadikoy Hospital
1 Department of Cardiovascular Surgery, Siyami Ersek Thoracic and Cardiovascular Surgery Center, Istanbul, Turkey
For reprint information contact: Sahin Senay, MD Tel: 90 533 310 5202 Fax: 90 216 337 9719 Email: sahinsenay{at}gmail.com, Ozlem Sitesi B Blok D: 25 Kosuyolu-Uskudar, Istanbul, Turkey.
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ABSTRACT
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Although an adverse influence of hyperoxemia during cardiopulmonary bypass is well documented, there is a wide range of oxygen settings during cardiopulmonary bypass, based mostly on trial and error. The aim of this study was to determine the optimal inspired oxygen fraction during cardiopulmonary bypass. Ninety patients undergoing isolated coronary artery bypass operations were randomly allocated to one of 3 groups of 30 each. In group 1, cardiopulmonary bypass was started with an inspired oxygen fraction of 0.40, increased to 0.60 during rewarming. These settings were 0.40 and 0.50 in group 2, and 0.35 and 0.45 in group 3. Samples for blood gas analysis were collected at defined time periods during the operation. PaO2 was significantly higher in groups 1 and 2 compared to group 3. All patients in group 1 and 88% of patients in group 2 suffered at least one episode of hyperoxemia during cardiopulmonary bypass, compared to 30% of patients in group 3. The differences were significant, and we concluded that to avoid hyperoxemia, inspired oxygen fraction should be kept at 0.35 during cardiopulmonary bypass and increased to 0.45 during rewarming.
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INTRODUCTION
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The majority of cardiac operations are still performed using cardiopulmonary bypass (CPB). Patients undergoing cardiac surgery with CPB are often thought to have tissue hypoxia. For this reason, it is usually assumed that a supranormal arterial oxygen tension (PaO2) will improve oxygen delivery to peripheral tissue, with an increased margin of safety. As a result of this tempting assumption, very high values of PaO2 are frequently encountered in routine clinical practice. However, excessively high PaO2 can be harmful. Animal studies have shown that oxygen reduces heart rate and cardiac output and increases systemic vascular resistance.1,2 These findings have been confirmed in patients with congestive heart failure, in whom the effect is more pronounced.3 Adverse influences of hyperoxemia (PaO2 > 180 mm Hg) on red blood cells and tissue oxygenation during CPB, and hence on perioperative complications and morbidity, have been reported.4–6 Although CPB has been used for more than half a century, there is still no consensus on the ideal fraction of inspired oxygen (FiO2) and PaO2. There seems to be a wide range of practice in relation to the optimum oxygen setting during CPB, and the perfusionist usually adjusts the oxygen by trial and error. The most frequently recommended FiO2 at the initiation of CPB is 0.80, to be decreased to 0.70–0.60 during hypothermia.7 However, with such an application, hyperoxemia seems to be inevitable.8 In this study, we aimed to determine the most appropriate FiO2 during CPB, which would lead to neither hypoxia nor hyperoxemia.
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PATIENTS AND METHODS
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After approval of the Acibadem Health Group ethics committee, 90 patients undergoing elective coronary artery bypass surgery were randomly allocated to one of 3 groups of 30 each. In group 1, CPB was started with a FiO2 of 0.40 and increased to 0.60 during rewarming. These settings were 0.40 and 0.50 in group 2, and 0.35 and 0.45 in group 3. All patients were operated on using the same anesthetic regime and surgical techniques. The premedication was midazolam, and anesthesia consisted of a combination of fentanyl, midazolam, and pancuronium. After tracheal intubation, mechanical ventilation was started with oxygen and nitrogen, and anesthesia was maintained with midazolam and vecuronium infusion and inhaled sevoflurane. A microporous hollow-fiber membrane oxygenator (D 708 Simplex III; Dideco, Mirandola, Italy) was used for extracorporeal circulation. A volume of 1,300–1,500 mL of Ringer’s lactate solution was used for priming. Pump flow was kept at 2.0 L·min–1·m–2 during hypothermic (32°C) CPB, and increased to 2.5 L·min–1·m–2 during the rewarming period. Sweep gas flow was kept at 1.5 L·min–1·m–2, and hematocrit between 25% and 30%. Samples for blood gas analysis were collected at T1: before CPB, T2: 10 min after initiation of CPB, T3: 20 min after initiation of CPB, and T4: at the end of the rewarming period. Blood gas analyses were carried out with an ABL 700 analyzer (Radiometer, Copenhagen, Denmark) using the alpha-stat protocol. Swan-Ganz catheterization was not used in any patient; blood samples for mixed venous gas analysis were collected from the pump line from the right atrium during CPB at T2, T3, and T4, and oxygen extraction ratios were measured. Outcome parameters were recorded. Hyperoxemia was defined as PaO2 exceeding 180 mm Hg.5 Hypoxemia was defined as PaO2 below 60 mm Hg.9 All patients were managed by the same surgical and anesthesiology teams.
The results were analyzed with the chi-squared test (or Fisher’s exact test where applicable), and the independent samples t test. Statistical analysis was performed using SPSS statistical software (SPSS, Inc., Chicago, IL, USA). Values of p < 0.05 were considered to be statistically significant. All data are presented as mean ± standard deviation.
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RESULTS
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All 3 groups were comparable in terms of age, sex, body mass index, CPB time, and aortic cross clamp time. The pH, pCO2, SaO2 (Table 1
), hematocrit, and lactate levels (Table 2) were similar in all groups at all time points. The PaO2 values were significantly higher in groups 1 and 2 compared to group 3 during CPB (Table 1). All patients in group 1 and 88% of those in group 2 suffered at least one episode of hyperoxemia during CPB, compared to 30% of patients in group 3 (p < 0.0001). Hypoxemia (PaO2 < 60 mm Hg) was not encountered in any patient. There were no significant differences in oxygen extraction ratios among the 3 groups (Table 1). No minor or major neurological or renal complications occurred. The intensive care unit stay was 20.9 ± 6.6, 21.9 ± 5.9, and 22.1 ± 7.1 hr, and hospital stay was 5.3 ± 2.7, 5.5 ± 2.9, and 5.2 ± 2.2 days in groups 1, 2, and 3, respectively; these differences were not significant. There was no mortality in any group.
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DISCUSSION
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Peripheral tissue perfusion is disturbed and reduced during hypothermic CPB with both reduced flow and a continuous flow pattern. Under such circumstances, it may be tempting to assume that a higher PaO2 would provide improved oxygen delivery to peripheral tissue and an increased margin of safety. In fact, hyperoxemia increases global oxygen delivery and oxygen saturation in mixed venous blood during CPB.5 However, this increase is not associated with improved tissue perfusion or clinical outcome.4
To determine the oxygen extraction ratio during CPB, one can use the formula: ExO2 = (SaO2–SvO2)/SaO2, where ExO2 = oxygen extraction, SaO2 = arterial blood oxygen saturation (%), and SvO2 = venous blood oxygen saturation.10 If it is assumed that SaO2 = 100 and SaO2–SvO2 = 30 (100 – 70), ExO2 is found to be 30%, which means a threefold safety margin for oxygen consumption during CPB. In their in vivo study, Parolari and colleagues10 showed that oxygen extraction is 19% during hypothermia and increases to 27% during rewarming, which reflects a 3 to 4-fold safety margin. We did not find a significant difference in oxygen extraction ratios between groups in different time periods. Therefore, oxygen extraction ratios were not affected by FiO2. The lowest SaO2 encountered in all groups was 96%. When this value is entered into the formula above, it is obvious that the arterial oxygen content is still sufficient for adequate tissue oxygenation, and it is not necessary to have very high oxygen levels for the sake of safety. Indeed, hyperoxemia is associated with many side effects. Arterialized blood with oxygen partial pressure in excess of the normal range has been implicated in disturbed capillary flow, decreased cardiac index, and increased systemic vascular resistance, hemolysis, and microaeroemboli.1,5,7 Moreover, in several investigations in which tissue oxygenation was studied, decreased oxygenation, sometimes even to hypoxic levels, together with signs of maldistribution of capillary flow was found as a response to hyperoxemia.5,11–13
Another harmful effect of hyperoxemia is reported by Pizov and colleagues; they have determined a larger increase of the proinflammatory cytokines in the patients treated with 100% oxygen compared with 50% oxygen group4. A delayed recovery in patients treated with 100% oxygen was reported in this study. The use of a high FiO2 in the perioperative period in a general surgical population has been reported to be associated with increased surgical site infection.14
On the other hand, we have known for years that on reperfusion, oxygen is detrimental; yet we still have the arterial blood PaO2 up to 300 or 375 mm Hg when the cross clamp is removed. Ihnken and colleagues15 have shown that hyperoxemic CPB during cardiac operations in adults results in oxidative myocardial damage related to oxygen-derived free radicals and nitric oxide. In their prospective randomized double-blind study, hyperoxemic bypass resulted in higher levels of polymorphonuclear leukocyte elastase, creatine kinase, lactic dehydrogenase, antioxidants, malondialdehyde, and nitrate in coronary sinus blood, as well as a reduction in lung vital capacity and forced 1-second expiratory volume compared with normoxemic management. The clinical reflections of these findings were 57% longer duration of ventilator support and 1 day longer hospital stay.15 In recent years, more data have been accumulating on the cardioprotective effect of lowering oxygen tension after aortic declamping on CPB.16,17 Before this study, it was our policy to initiate CPB with an FiO2 of 0.60 and increase it to 0.70 during rewarming. However, very high PaO2 values were being encountered with this setting, leading to adjustment of oxygen settings based on trial and error and repeated blood gas analyses.
There are two limitations of this study. Firstly, arterial partial oxygen pressure does not always reliably inform about tissue oxygen delivery or extraction, especially in low perfusion states. Despite adequate oxygen delivery, some regional hypoxia may occur as a consequence of CPB. However, this hypoxia occurs mainly late after the termination of CPB, as shown by Niinikoski and colleagues,18 and reaches its maximum level at 8 hr postoperatively. They also speculated that during the first few hours in the intensive care unit, visceral and peripheral oxygenation and perfusion variables reflected hypoperfusion of tissues, coinciding with the period of greatest vulnerability to hemodynamic disasters and cardiac arrhythmias. In our study, the pump flow was kept constant and lactate levels (widely used to assess the adequacy of tissue perfusion) were measured throughout CPB to detect tissue hypoxia. Lactate levels did not differ among the groups. On the basis of this finding, one may assume that no tissue hypoxia occurred and so the adverse affects of hyperoxemia were not apparent. However, interpretation of blood lactate levels during CPB is limited by several confounding variables. Raper and colleagues19 reported that the lactate level after CPB, which was within the normal range on admission to the intensive care unit, reached its maximum 13 hr later. They also speculated that this increase was primarily related to systemic vasodilation and reduced oxygen extraction, rather than inadequate oxygen delivery during CPB. Secondly, although the power of the current study is 98.5%, the study population was not sufficient for an outcome analysis, although the measured major outcome parameters were similar in all groups. Further clinical studies are needed to document a possible benefit on outcome from avoiding hyperoxemia during CPB.
It was concluded from these findings that by adjusting FiO2 to 0.35 at the initiation of CPB and then increasing it to 0.45 during rewarming, hyperoxemia is avoided without a significant risk of hypoxia.
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ABSTRACT
INTRODUCTION
