Perfusion

Edema is a common morbidity following cardiopulmonary bypass (CPB) and can result in injury to many organs, including the heart, lungs, and brain. Generalized edema is also common and can lead to increased post-operative hospital stay and other morbidities. Pediatric patients are more susceptible to post-CPB edema and the consequences are more severe for this population. Hemodilution and systemic inflammatory responses are two suspected causes of CPB-related edema; however, the mechanisms involved are far from understood. Also, the common strategies to improve edema have not been completely successful and there is a need for new strategies at maintaining a fluid balance of patients as close to physiological as possible, especially for pediatric patients. An integrative approach to understanding edema is necessary as the forces involved in fluid homeostasis are dynamic and interdependent. Therefore, this review will focus on the physiology of fluid homeostasis and the pathologies of fluid shifts during CPB which lead to general edema as well as tissue-specific edema.

The aim of the study was to investigate if acute renal failure (ARF) following cardiac surgery is influenced by CPB perfusion pressure and to determine risk factors of ARF. Our research consisted of two studies. In the first study, 179 adult patients with normal preoperative renal function who had been subjected to cardiac surgery on CPB were randomized into three groups. The mean perfusion pressure (PP) during CPB in Group 65 (68 patients) was 60–69.9 mmHg, in Group 55 (59 patients) – lower than 60 mmHg and in Group 75 (52 patients) – 70 mmHg and higher. We have analyzed postoperative variables: central venous pressure, the need for diuretics, urine output, fluid balance, acidosis, potassium level in blood serum, the need for hemotransfusions, nephrological, cardiovascular and respiratory complications, duration of artificial lung ventilation, duration of stay in ICU and in hospital, and mortality. In the second study, to identify the risk factors for the development of ARF following CPB, we retrospectively analysed data of all 179 patients, divided into two groups: patients who developed ARF after surgery (group with ARF, n = 19) and patients without ARF (group without ARF, n = 160). We found that urine output during surgery was statistically significantly lower in Group 55 than in Groups 65 and 75. The incidence of ARF in the early postoperative period did not differ among the groups: it developed in 6% of all patients in Group 65, 4% in Group 55 and 6% in Group 75. There were no differences in the rate of other complications (cardiovascular, respiratory, neurological disorders, bleeding, etc) among the groups. There were 19 cases of ARF (10.6%), but none of these patients needed dialysis. We found that age (70.0 ± 7.51 vs. 63.5 ± 10.54 [standard deviation, SD], P = 0.016), valve replacement and/or reconstruction surgery (57.9% vs. 27.2%, P = 0,011), combined valve and CABG surgery (15.8% vs. 1.4%, P = 0.004), duration of CPB (134.74 ± 62.02 vs. 100.59 ± 43.99 min., P = 0.003) and duration of aortic cross-clamp (75.11 ± 35.78 vs. 53.45 ± 24.19 min., P = 0.001) were the most important independent risk factors for ARF. Cardiopulmonary bypass perfusion pressure did not cause postoperative renal failure. The age of patient, valve surgery procedures, duration of cardiopulmonary bypass and duration of aorta cross-clamp are potential causative factors for acute renal failure after cardiac surgery.

Although the definitions of renal dysfunction vary, loss of renal function is a common complication following cardiac surgery using cardiopulmonary bypass (CPB). When postoperative dialysis is required, mortality is approximately 50%. CPB-accompanied hemodilution is a major contributing factor to renal damage as it notably reduces oxygen delivery by reducing the oxygen transport capacity of the blood as well as disturbing the microcirculation. To minimize hypoxemic damage during CPB, lowering of body temperature is applied to reduce the patient’s metabolic rate. At present, however, temperature management during elective adult cardiac surgery is shifting from moderate hypothermia to normothermia. To determine whether the currently accepted levels of hemodilution during CPB can suffice the normothermic patient’s high oxygen demand, we focused this study on renal physiology and postoperative renal function. Hemodilution reduces the capillary density through a diminished capillary viscosity, thereby, redistributing blood from the renal medulla to the renal cortex. As the physiology of the renal medulla makes it a hypoxic environment, this part of the kidney appears to be especially at risk for hypoxic damage caused by a hemodilution-induced lowered oxygen transport and oxygen delivery. In addition, hemodilution is also likely to disturb the hormonal systems regulating renal blood distribution. Clinical studies, mostly of retrospective or observational nature, show that perioperative nadir hematocrit levels lower than approximately 24% are associated with an increased risk to develop postoperative renal failure. A better comprehension of the cause-and-effect relation between low perioperative hematocrits and loss of postoperative renal function may enable more effective renal protective strategies.

The aim of this study was to monitor and compare the changes in metabolism and blood flow in the skeletal muscles during cardiac operations performed with cardiopulmonary bypass (CPB) and operations without CPB (off-pump) by means of interstitial microdialysis (Figure 1). Surgical revascularization, coronary artery bypass grafting (CABG), was performed in 40 patients randomized to two groups. Twenty patients (On-Pump Group) were operated on using CPB, 20 patients (Off-Pump Group) were operated on without CPB. Interstitial microdialysis was performed by 2 probes of a CMA 60 (CMA Microdialysis AB, Solna, Sweden) inserted into the patient’s deltoid muscle. Microdialysis measurements were performed at 30-minute intervals. Glucose, lactate, pyruvate and glycerol as markers of basic metabolism and tissue perfusion were measured in samples from the first probe, using a CMA 600 Analyzer (CMA Microdialysis AB). Blood flow through the interstitium was monitored by means of dynamic microdialysis of ethanol as a flow-marker in the dialysates taken from the second probe (ethanol dilution technique). Results in both the groups were statistically processed and compared. Both the groups were similar in respect of preoperative characteristics. Dynamic changes of interstitial concentrations of the measured analytes were found in both the patient groups (on-pump vs. off-pump) during the operation. There was no significant difference in dialysate concentrations of glucose and lactate between the groups. Significant differences were detected in pyruvate and glycerol interstitial concentrations, lactate/pyruvate ratio and lactate/glucose ratio between the on-pump vs. off-pump patients. In the Off-Pump Group, pyruvate concentrations were higher and the values of concentrations of glycerol lower. The lactate/pyruvate ratio and the lactate/glucose ratio, indicating the aerobic and anaerobic tissue metabolism status, were lower in the Off-Pump Group. There was no significant difference in dialysate concentrations of ethanol as a flow-marker during the surgery in either of the groups. There was no statistically significant difference between the groups (On-Pump Group vs. Off-Pump Group) comparing the postoperative clinical outcome (ICU stay, ventilation duration, length of hospital stay). The dynamic changes in the interstitial concentrations of the glucose, glycerol, pyruvate and lactate were found in both the groups of patients (On-Pump Group and Off-Pump Group), but there was no difference in local blood flow when the ethanol dilution technique was used. These results showed significantly higher aerobic metabolic activity of the peripheral tissue of patients in the Off-Pump Group vs. the On-Pump Group during the course of cardiac revascularization surgery. Results suggest that extracorporeal circulation, cardiopulmonary bypass, compromises peripheral tissue (skeletal muscles) energy metabolism. These changes have no impact on the postoperative clinical outcome; no significant difference between the groups was found.

Patients undergoing open-heart surgery may, post-operatively, suffer from neurological disorders due to microbubbles created during extracorporeal circulation. Venous air is not completely removed in open hard-shell venous reservoirs. We, therefore, investigated the relationship between venous reservoir blood level and the amount of microbubbles in different commercially available reservoirs for comparison and determination of safe level. An in vitro flow loop with a heart-lung machine was used to compare three different reservoirs (Maquet, Sorin and Medtronic) at different levels. Microbubbles were measured after the reservoir and after the arterial filter with a GAMPT BCC200 detector. Microbubble count and volume were significantly higher with decreasing reservoir level (p = 0.014), but not as much as earlier studies have shown. Reducing the level from 1000 ml to 250 ml resulted in a 12.4% increase in bubble volume after the reservoir and 40.2% after the arterial filter. There was an almost linear trend towards more bubble volume with decreasing reservoir level (R2 = 0.98-0.83). There was a significant difference in microbubbles between the 3 tested reservoirs, up to 32.6%, p < 0.001 measured after the reservoir. Bubble volume from the Sorin reservoir was markedly lower after the arterial filter than from the Medtronic and Maquet reservoirs (up to 60 times p < 0.001). A lower reservoir level results in a moderate rise in microbubbles passing the reservoir. The minimum levels recommended by the manufacturers are safe. There was a significant difference in bubbles between the different reservoirs, especially after the arterial filter.

Although aprotinin is partially excreted unchanged in the urine, its primary site of metabolism is in the renal lysosomes following proximal tubule resorption. This study tested the hypothesis that plasma aprotinin concentration varies with cardiopulmonary bypass conditions. Thirty-two piglets (weight 13.2 ± 1.9 kg) received an aprotinin initial dose of 30,000 KIU/kg, a maintenance infusion of 10,000 KIU/kg/h, with a cardiopulmonary bypass (CPB) prime of 30,000 KIU/kg. Aprotinin infusion was terminated at the end of CPB and stopped during hypothermic circulatory arrest (HCA). Piglets were randomized to four groups (n = 8 per group): HCA, 60-minute period at 15°C; low-flow (LF), 10 mL/kg/min low-flow CPB at 25°C; full flow (FF), full flow CPB at 37°C; control at 37°C without CPB. Blood samples were collected at 7 time points: after induction of anesthesia (baseline), after initial dose, 10, 50 and 115 min after start of CPB, just before end of CPB and 30 min after CPB. Plasma aprotinin levels were determined by modified functional assays. Aprotinin levels in the control group were significantly lower at each point after start of CPB than all groups with CPB (p < .001). In particular, during the reperfusion period, aprotinin levels were higher in HCA and LF groups than FF group (p < .05). Throughout CPB, aprotinin levels in the HCA group remained unchanged (p > .40). Bypass conditions affect plasma aprotinin concentration. Recently reported renal and neurological complications with aprotinin use during CPB may reflect excessive dosing and point to the need for real-time monitoring.

We have reviewed the results of our experience with the use of miniaturized (Mini-CPB) versus conventional (C-CPB) cardiopulmonary bypass in coronary artery bypass surgery (CABG). This study included 365 patients who underwent CABG with C-CPB and 101 patients with Mini-CPB. In-hospital mortality was lower in the C-CPB group (1.4% vs. 3.0%, P = 0.38). A better, but not statistically significant, immediate outcome was observed in the C-CPB group as indicated by a shorter length of stay in the intensive care unit as well as a lower incidence of combined adverse end-point. However, this was probably due to significantly higher operative risk in the Mini-CPB group (logistic EuroSCORE: 8.5 ± 10.0 vs. 4.6 ± 7.1, P < 0.0001). Seventy-seven propensity score-matched pairs had similar immediate postoperative results after Mini-CPB and C-CPB (30-day mortality: 1.3% vs. 1.3%; stroke: 0% vs. 0%; intensive care unit stay ≥5 days: 6.5% vs. 9.1%; combined adverse events: 14.3% vs. 11.7%). Mini-CPB achieves similar results to C-CPB in patients undergoing isolated CABG. The potential efficacy of Mini-CPB is expected to be more evident in high-risk patients or in complex cardiac surgery requiring much longer cardiopulmonary perfusion.

The operating theatre exposes patients to myriad potential agents which could result in a life-threatening anaphylactic reaction. Anaesthetic drugs, blood products, and latex are only some of the possible allergens. Reactions are deemed to be anaphylactic when immediate sensitivity is combined with cardiovascular collapse. A patient who had a known allergy to shellfish presented for first time cardiopulmonary bypass. The perfusion team were concerned that there was a realistic possibility that an adverse reaction to protamine could occur. Anaphylactic reactions to protamine in patients allergic to fish have been reported. The anaesthetic team were informed and the necessary precautions taken. We report on the outcome for our patient and also discuss other risk factors and the types of reactions that can result when an adverse reaction to protamine occurs.