**2. Patients, materials and methods**

The study was carried out at the Department of Cardiac Surgery, University Hospital and Faculty of Medicine in Hradec Kralove, Charles University in Prague, Czech Republic. The study was approved by the university Ethics Committee. Patients were given a prior de‐ tailed explanation of the study and signed an informed consent.

### **2.1. Patients**

The sample included 40 patients with ischemic heart disease (32 men and 8 women). All pa‐ tients underwent elective cardiac surgery. The exclusion criteria were concomitant surgery, an emergency procedure, patients with local, systemic infection or inflammation, severe left ventricular dysfunction (ejection fraction < 25%), renal failure (serum creatinine >180 μmol l -1 or active renal replacement therapy).

Volume constant perfusion (perfusion without a reservoir) is a major advantage of mini CPB, but it can be associated with significant problems. The calculated blood flow (pump flow) must often be reduced to compensate for the volume in case of lower venous return during perfusion. Other reasons for reduction in pump flow are an increase in arterial pres‐

Delivery of oxygen to the tissues is equally dependent on blood flow and the O2 content of blood. Reduction of blood flow can decrease optimal tissue oxygenation. Inadequate oxy‐ genation and perfusion can be associated with severe pathological peripheral tissue changes

It is difficult to assess local changes in perfusion or blood circulation in the periphery. The direct measurement of blood flow through separate organs or skeletal muscles during car‐ diac surgery is both technically difficult and ethically unacceptable. Evaluation of the stand‐ ard biochemical and hemodynamic parameters (blood pressure, blood lactate, heart rate, O2 saturation in the capillary bed, diuresis, etc.) yields for general results but not for regional

For this purpose, direct continuous measurement of interstitial tissue oxygen tension (ptO2) of a skeletal muscle, as a typical peripheral tissue, was used in this study. Tissue oxygen ten‐

Oxygen tension was measured with a special optical multiparametric sensor inserted into the patient´s deltoid muscle. The sensor is based upon the principle of fluorescence quench‐ ing whereby the intensity of a fluorescent optical emission form, an indicator, is quenched (reduced) in the presence of oxygen. Oxygen from the surrounding blood equilibrates with the sensor materials and quenches the fluorescent light. This method was introduced into brain and liver perfusion measurement but it has not been used in connection with cardio‐

The present study was designed to evaluate changes in peripheral tissue (skeletal muscle) oxygenation during cardiac surgery and to compare tissue perfusion in relation to blood

The study was carried out at the Department of Cardiac Surgery, University Hospital and Faculty of Medicine in Hradec Kralove, Charles University in Prague, Czech Republic. The study was approved by the university Ethics Committee. Patients were given a prior de‐

The sample included 40 patients with ischemic heart disease (32 men and 8 women). All pa‐ tients underwent elective cardiac surgery. The exclusion criteria were concomitant surgery,

sion reflects the adequacy of regional tissue oxygenation and perfusion [11,12].

sure and flooding of the operating field with blood.

associated with clinical complications [1,9,10].

changes [1,3,9].

100 Artery Bypass

**2.1. Patients**

pulmonary bypass until now.

flow during standard CPB versus mini CPB.

**2. Patients, materials and methods**

tailed explanation of the study and signed an informed consent.

The patients were randomized to two groups. Group A, consisting of 20 patients who un‐ derwent the conventional myocardial revascularization, coronary artery bypass grafting (CABG) using standard CPB and Group B, consisting of 20 patients who underwent coro‐ nary surgery using miniaturized CPB (Figure 1).

**Figure 1.** Coronary artery bypass grafting using cardiopulmonary bypass

Patient preoperative characteristics (Table 1), operative (Table 2) and postoperative data (Ta‐ ble 3) were prospectively recorded. The differences between groups (age, accompanying dis‐ ease) were not statistically significant (Table 1). All routine therapeutic and monitoring steps commonly used with this diagnosis were performed. After clinical and angiographic evalua‐ tion the patients were randomly assigned to the study (n = 40).


**Group A (n=20)**

**Blood loss per 24 hours (ml)**

> **Blood transfusion (units)**

**Hospital lenght of stay (d)**

**2.2. Anesthetic technique**

**2.3. Technique of CPB**

+

*2.3.1. Standard CPB technique (Group A)*

neutralized with protamin in a 1:1 ratio.

**Table 3.** Postoperative characteristics of Group A (standard CPB) and Group B (mini CPB)

g). In all cases the surgical approach was through median sternotomy.

**IM** 0 0 n.s. **Strokes** 1 0 n.s. **Atrial fibrilation** 6 2 <0,001 **30-d mortality** 0 0 n.s. **Low cardiac output** 2 1 n.s. **Renal failure** 0 0 n.s.

Peripheral Tissue Oxygenation During Standard and Miniaturized Cardiopulmonary Bypass (Direct Oxymetric Tissue

**ICU stay (hours)** 70 ± 68 112 ± 225 n.s.

The anesthetic managements, CPB and surgical procedures were standardized in both groups. Anesthesia was induced with intravenous thiopenthal or midazolam and sufentanyl with muscle relaxation using cisatracurium. Anesthesia was maintained by an infusion of cisatracurium, sufentanyl and propofol at doses sufficient to keep the patient adequately an‐ esthetized and hemodynamically stable. Isoflurane was added in the inhaled air. Antibiotic prophylaxis was given in accordance with the standard protocol (Unasyn, Pfizer, Italy; 3x1.5

Cardiopulmonary bypass was established by standard aortic cannulation and two-stage ve‐ nous cannulation of the right atrium. Antegrade cold blood cardioplegia (blood and St. Tho‐ mas´ solution in a ratio of 4:1) and topical cooling for the arrested heart and myocardial protection were employed. Anticoagulation was induced before CBP with heparin (2.5 mg

kg-1), and the activated clotting time (ACT over 480 seconds) was monitored. Heparin was

The extracorporeal circuit consisted of a hollow fiber membrane oxygenator (PrimO2x, Sorin Group, Italy) and roller pump with a non-pulsatile flow (Stockert S3, Sorin Group, Germa‐ ny) in an open modification with 40.0 μm arterial line filter (Dideco Micro 40R, Mirandola,

**Group B**

685 ± 342 861 ± 552 n.s.(0.57)

2.5 ± 1.4 2.7 ± 1.2 n.s.

16.4 ± 6.8 16.2 ± 5.4 n.s.

**(n=20) p-value**

Perfusion Monitoring Study) http://dx.doi.org/10.5772/54300 103

**Table 1.** Preoperative characteristics of Group A (standard CPB) and Group B (mini CPB)


**Table 2.** Operative characteristics of Group A (standard CPB) and Group B (mini CPB)

Peripheral Tissue Oxygenation During Standard and Miniaturized Cardiopulmonary Bypass (Direct Oxymetric Tissue Perfusion Monitoring Study) http://dx.doi.org/10.5772/54300 103


**Table 3.** Postoperative characteristics of Group A (standard CPB) and Group B (mini CPB)

#### **2.2. Anesthetic technique**

**Group A (n=20)**

**Body mass index(kg.m-2)**

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**Prior myocardial infarction**

**Chronic obstructive airway disease**

> **No. of distal anastomoses**

**Lowest temperature (ºC)**

**Table 2.** Operative characteristics of Group A (standard CPB) and Group B (mini CPB)

**Table 1.** Preoperative characteristics of Group A (standard CPB) and Group B (mini CPB)

**Male sex (%)** 17 (85%) 15 (75%) n.s.

**Ejection fraction(%)** 57.8 ± 9.8 56.2 ±12.7 n.s.

**Prior PCI** 4 4 n.s.

**Hypertension** 18 18 n.s. **Diabetes mellitus** 7 6 n.s.

**Euroscore** 5.2 ± 4.7 (1.4-15.1) 4.6 ± 3.5 (0.9-15.6) n.s.

**Group A (n=20)**

**Operation time (min)** 254 ± 21.7 247 ± 58.1 n.s.

**Aortic crossclamp (min)** 48.9 ± 14.5 45.4 ± 14.8 n.s.

**Flow calculated (l.min-1)** 4.7 ± 0.39 4.6 ± 0.45 n.s.

**Flow real (l.min-1)** 4.9 ± 0.41 3.5 ± 0.51 <0,001

**Mean hematocrit (%)** 25.3 ± 1.1 31.0 ± 2.3 <0,001

**Priming (ml)** 1501 ± 44 837 ± 205 <0,001

**CPB time (min)** 87.4 ± 21.7 75.7 ± 20.9 n.s.

**Age (y)** 69 ± 5.8 67 ± 6.8 n.s.

**Group B**

29 ± 4.9 28 ± 4.3 n.s.

12 12 n.s.

3 2 n.s.

**Group B**

2.9 ± 0.8 2.7 ± 0.7 n.s.

35.5 ± 0.4 35.7 ± 0.7 n.s.

**(n=20) p-value**

**(n=20) p-value**

The anesthetic managements, CPB and surgical procedures were standardized in both groups. Anesthesia was induced with intravenous thiopenthal or midazolam and sufentanyl with muscle relaxation using cisatracurium. Anesthesia was maintained by an infusion of cisatracurium, sufentanyl and propofol at doses sufficient to keep the patient adequately an‐ esthetized and hemodynamically stable. Isoflurane was added in the inhaled air. Antibiotic prophylaxis was given in accordance with the standard protocol (Unasyn, Pfizer, Italy; 3x1.5 g). In all cases the surgical approach was through median sternotomy.

### **2.3. Technique of CPB**

#### *2.3.1. Standard CPB technique (Group A)*

Cardiopulmonary bypass was established by standard aortic cannulation and two-stage ve‐ nous cannulation of the right atrium. Antegrade cold blood cardioplegia (blood and St. Tho‐ mas´ solution in a ratio of 4:1) and topical cooling for the arrested heart and myocardial protection were employed. Anticoagulation was induced before CBP with heparin (2.5 mg + kg-1), and the activated clotting time (ACT over 480 seconds) was monitored. Heparin was neutralized with protamin in a 1:1 ratio.

The extracorporeal circuit consisted of a hollow fiber membrane oxygenator (PrimO2x, Sorin Group, Italy) and roller pump with a non-pulsatile flow (Stockert S3, Sorin Group, Germa‐ ny) in an open modification with 40.0 μm arterial line filter (Dideco Micro 40R, Mirandola, Italy). The oxygenator and tubing system were primed with a mixture of crystalloid (Hart‐ mann´s solution), colloids (Voluven), 10% Mannitol solution, 8.4% sodium bicarbonate, magnesiumsulphur solution, 5.000 IU of heparin. The CPB involved normothermia and cal‐ culated blood flow 2.4 - 2.8 l.m-2. Mean arterial pressure during CPB was maintained at 50 to 75 mmHg and hematocrit above 0.22%. The acid base status was maintained using the al‐ pha-stat perfusion strategy (Figure 2).

tection of the myocardium during surgery (blood cardioplegia and topical cooling) was the

Peripheral Tissue Oxygenation During Standard and Miniaturized Cardiopulmonary Bypass (Direct Oxymetric Tissue

Perfusion Monitoring Study) http://dx.doi.org/10.5772/54300 105

same as in Group A (Figure 3, 4).

**Figure 3.** Miniaturized integrated CPB system (Synergy Sorin, Sorin Group, Italy)

**Figure 2.** Standard cardiopulmonary bypass equipment

#### *2.3.2. Miniaturized CPB technique (Group B)*

Miniaturized CPB was established using aortic cannulation and a two-stage venous cannu‐ lation of the right atrium. A fully integrated minisystem (Synergy SorinR, Sorin Group, Ita‐ ly) consisted of a centrifugal pump, membrane oxygenator, 40.0 μm arterial line filter and a venous bubbletrap. Cardiotomy suction and vents were not used. The whole system was a closed loop with the internal surface treated with a phosphorylcholin coat

(PH.I.S.I.O, Sorin Group, Italy) and very short tubing. The priming solution, heparinization, calculated blood flow, temperature and surgery technique were identical to the standard CPB (Group A). While initiating CPB, crystalloid priming was retrogradely flushed with blood from the arterial line to minimize hemodilution (retrograde autologus priming). Pro‐ Peripheral Tissue Oxygenation During Standard and Miniaturized Cardiopulmonary Bypass (Direct Oxymetric Tissue Perfusion Monitoring Study) http://dx.doi.org/10.5772/54300 105

tection of the myocardium during surgery (blood cardioplegia and topical cooling) was the same as in Group A (Figure 3, 4).

Italy). The oxygenator and tubing system were primed with a mixture of crystalloid (Hart‐ mann´s solution), colloids (Voluven), 10% Mannitol solution, 8.4% sodium bicarbonate, magnesiumsulphur solution, 5.000 IU of heparin. The CPB involved normothermia and cal‐ culated blood flow 2.4 - 2.8 l.m-2. Mean arterial pressure during CPB was maintained at 50 to 75 mmHg and hematocrit above 0.22%. The acid base status was maintained using the al‐

Miniaturized CPB was established using aortic cannulation and a two-stage venous cannu‐ lation of the right atrium. A fully integrated minisystem (Synergy SorinR, Sorin Group, Ita‐ ly) consisted of a centrifugal pump, membrane oxygenator, 40.0 μm arterial line filter and a venous bubbletrap. Cardiotomy suction and vents were not used. The whole system was a

(PH.I.S.I.O, Sorin Group, Italy) and very short tubing. The priming solution, heparinization, calculated blood flow, temperature and surgery technique were identical to the standard CPB (Group A). While initiating CPB, crystalloid priming was retrogradely flushed with blood from the arterial line to minimize hemodilution (retrograde autologus priming). Pro‐

closed loop with the internal surface treated with a phosphorylcholin coat

pha-stat perfusion strategy (Figure 2).

104 Artery Bypass

**Figure 2.** Standard cardiopulmonary bypass equipment

*2.3.2. Miniaturized CPB technique (Group B)*

**Figure 3.** Miniaturized integrated CPB system (Synergy Sorin, Sorin Group, Italy)

### **2.4. Monitoring technique**

Before the surgical procedure, at the time of anesthesia introduction, the optical multipara‐ metric sensor (NeuroventR PTO, Raumedic AG, Germany) (Figure 5) was inserted under sterile conditions into the right deltoid muscle without the use of local anesthesia (Figure 6). Continuous measurement of interstitial tissue oxygen tension (ptO2) was made during the surgical procedure and postoperatively by a special monitoring system (DataloggerR MPR2 logO, Raumedic AG, Germany) (Figure 7,8).

**Figure 6.** Sensor inserted into the right deltoid muscle

Peripheral Tissue Oxygenation During Standard and Miniaturized Cardiopulmonary Bypass (Direct Oxymetric Tissue

Perfusion Monitoring Study) http://dx.doi.org/10.5772/54300 107

**Figure 7.** Analyzer Dattaloger® MPR2 logO (Raumedic AG, Germany)

**Figure 8.** Analyzer Dattaloger® MPR2 logO (Raumedic AG, Germany) during CPB

**Figure 4.** Miniaturized integrated CPB system (Synergy Sorin, Sorin Group, Italy) during surgery

**Figure 5.** Multiparametric sensor Neurovent® PTO (Raumedic AG, Germany)

Peripheral Tissue Oxygenation During Standard and Miniaturized Cardiopulmonary Bypass (Direct Oxymetric Tissue Perfusion Monitoring Study) http://dx.doi.org/10.5772/54300 107

**Figure 6.** Sensor inserted into the right deltoid muscle

**2.4. Monitoring technique**

106 Artery Bypass

logO, Raumedic AG, Germany) (Figure 7,8).

Before the surgical procedure, at the time of anesthesia introduction, the optical multipara‐ metric sensor (NeuroventR PTO, Raumedic AG, Germany) (Figure 5) was inserted under sterile conditions into the right deltoid muscle without the use of local anesthesia (Figure 6). Continuous measurement of interstitial tissue oxygen tension (ptO2) was made during the surgical procedure and postoperatively by a special monitoring system (DataloggerR MPR2

**Figure 4.** Miniaturized integrated CPB system (Synergy Sorin, Sorin Group, Italy) during surgery

**Figure 5.** Multiparametric sensor Neurovent® PTO (Raumedic AG, Germany)

**Figure 7.** Analyzer Dattaloger® MPR2 logO (Raumedic AG, Germany)

**Figure 8.** Analyzer Dattaloger® MPR2 logO (Raumedic AG, Germany) during CPB

Arterial blood pressure, blood flow during CPB, laboratory markers of tissue perfusion, blood gases and body temperature were recorded and analyzed as well.

On the other hand, a direct correlation between pumped blood flow and MAP (↓flow ≈↓MAP) was found during CPB in Group B. The value of ptO2 was continuously higher and independent at this time. A decrease in ptO2 levels without correlation to MAP was found

Peripheral Tissue Oxygenation During Standard and Miniaturized Cardiopulmonary Bypass (Direct Oxymetric Tissue

Perfusion Monitoring Study) http://dx.doi.org/10.5772/54300 109

Lower levels of ptO2 without correlation to MAP were analysed postoperatively in both groups and we observed a trend towards a reduced ptO2 during the first hours after admis‐

**Figure 9. Levels of ptO2, blood flow and MAP in Group A (standard CPB) in intervals** (Intervals: 1- 30 min. after incision, 2- 15 min. before CPB, 3- CPB, 4,5,6- à 20 min. of CPB, 7- end of crossclamp, 8- after 15 min., 9- end of CPB, 10-

Higher levels of ptO2 during and after CPB in comparison with initial levels were observed

A higher blood flow during perfusion was analysed in Group A and lower than calculated

Changes of ptO2 at this time compared with initial level are shown in Figure 11.

in Group B. A decrease in ptO2 levels after surgery was found in both groups.

Changes in flow (%) in time compared to calculated flow are shown in Figure 12.

during surgery after CPB as in Group A (Figure 10).

sion to the intensive care unit (Figure 9,10).

after 15 min., 11- end of surgery, 12,13,14- à 1 h. I.C.U.)

blood flow was found in Group B.

Data from the oxymetric catheter in all patients were compared at the following time inter‐ vals: 1) 30 min after incision, 2) 15 min before CPB, 3) CPB, 4,5,6- at 20 min intervals during CPB, 7) end of crossclamp, 8) 15 min. after release of crossclamp, 9) end of CPB, 10) 15 min after termination of CPB, 11) end of surgery, 12,13,14- at 1 h intervals in the I.C.U.

### **2.5. Statistical analysis**

Demographic and perioperative data are reported as number, means ± standard deviation (S.D.) or median. Comparisons between preoperative characteristics and perioperative data were made using the Student´s *t* test or the Mann-Whitney U-test and Kolmogorov-Smirnov test where appropriate. Values are expressed as means ± standard error of the mean (S.E.M.). Intergroup comparisons between two variables at the same time point were per‐ formed using the Mann-Whitney U-test. Group comparison was done using the Wilcoxon test for paired data.

The data were analyzed using the programs NCSS 2004 and Statistica. Differences were con‐ sidered statistically significant at the level of *P*<0.05.
