Hepatosplanchnic oxygenation is better preserved during mild hypothermic than during normothermic cardiopulmonary bypass

PURPOSE: To assess and compare the effects of normothermic and mild hypothermic cardiopulmonary bypass (CPB) on hepatosplanchnic oxygenation. METHODS: We studied 14 patients scheduled for elective coronary artery bypass graft surgery who underwent normothermic (>35 degrees C; group I, n=7) or mild hypothermic (32 degrees C; group II, n=7) CPB. After induction of anesthesia, a hepatic venous catheter was inserted into the right hepatic vein to monitor hepatic venous oxygen saturation (ShvO(2)) and hepatosplanchnic blood flow by a constant infusion technique that uses indocyanine green. RESULTS: The ShvO(2) decreased from a baseline value in both groups during CPB and was significantly lower at ten minutes and 60 min after the onset of CPB in group I (39.5 +/- 16.2% and 40.1 +/- 9.8%, respectively) than in group II (61.1 +/- 16.2% and 61.0 +/- 17.9%, respectively; P <0.05). During CPB, the hepatosplanchnic oxygen extraction ratio was significantly higher in group I than in group II (44.0 +/- 7.2% vs 28.7 +/- 13.1%; P <0.05). CONCLUSION: Hepatosplanchnic oxygenation was better preserved during mild hypothermic CPB than during normothermic CPB.     

Impairment of hepatosplanchnic oxygenation and increase of serum hyaluronate during normothermic and mild hypothermic cardiopulmonary bypass

Hepatic sinusoidal endothelial cells (SECs) are more vulnerable to hypoxia or hypothermia than hepatocytes. To test the hypothesis that hepatic venous desaturation during cardiopulmonary bypass (CPB) leads to impairment of SEC function, we studied the plasma kinetics of endogenous hyaluronate (HA), a sensitive indicator of SEC function, and hepatosplanchnic oxygenation during and after CPB. Twenty-five consecutive patients scheduled for elective coronary artery bypass graft surgery, who underwent normothermic (>35 degrees C; n = 15) or mild hypothermic (32 degrees C; n = 10) CPB participated in this study. A hepatic venous catheter was inserted into each patient to monitor hepatosplanchnic oxygenation and serum levels of HA concentration. Hepatic venous oxygen saturation decreased essentially to a similar degree during normothermic and mild hypothermic CPB. Hepatosplanchnic oxygen consumption and extraction increased during normothermic (P < 0.05), but not mild hypothermic, CPB. Both arterial and hepatic venous HA concentrations showed threefold increases during and after CPB in both groups. A positive correlation was found between hepatosplanchnic oxygen consumption and arterial HA concentrations during CPB, suggesting a role of changes in hepatosplanchnic oxygen metabolism in the mechanisms of increases in serum HA concentrations. The failure of the liver to increase HA extraction to a great degree suggests that a functional impairment of the SEC may contribute to the observed increase of serum HA. IMPLICATIONS: Hepatic sinusoidal endothelial cells (SECs) are pivotal in the regulation of sinusoidal blood flow. This study showed that SEC function might be impaired during and after cardiopulmonary bypass, irrespective of the temperature management.     

Greater neuromuscular blocking potency of atracurium during hypothermic than during normothermic cardiopulmonary bypass.

Previous studies drew attention to the greater neuromuscular blocking potency of atracurium during, than before or after, hypothermic cardiopulmonary bypass (CPB) while disregarding the periods of normothermic perfusion. We recorded the evoked twitch tension in 15 patients during nitrous oxide/narcotic anesthesia who were undergoing open heart surgery. Atracurium was injected as an initial bolus dose of 460 micrograms/kg. Waning neuromuscular blockade was enhanced by repeat injections of 138 micrograms/kg whenever the twitch tension attained 25% of control. During hypothermic (< 32 degrees C) and normothermic (> 34 degrees C) CPB, the times of onset of the maintenance doses were 57% and 18% longer, respectively, than before CPB (P < 0.05). Maintenance doses of atracurium were required every 24 +/- 4 min (mean +/- SD) before CPB, every 45 +/- 8 min (P < 0.05) during hypothermia, every 22 +/- 3 min during normothermic perfusion, and every 23 +/- 3 min after CPB. In conclusion, the patients' changing demand of atracurium paralleled the changes of temperature rather than the institution and cessation of CPB.     

Effects of hypothermic and normothermic cardiopulmonary bypass on brain oxygenation.

BACKGROUND: In this study, we assessed the effects of normothermia and hypothermia during cardiopulmonary bypass (CPB) both on internal jugular venous oxygen saturation (SjvO2) and the regional cerebral oxygenation state (rSO2) estimated by near infrared spectroscopy (NIRS). METHODS: Thirty patients scheduled for elective coronary artery bypass graft surgery (CABG) were randomly divided into two groups. Group 1 (n = 15) underwent surgery for normothermic (> 35 degrees C) CPB, and group 2 (n = 15) underwent surgery for hypothermic (30 degrees C) CPB, and alpha-stat regulation was applied. A 4.0-French fiberoptic oximetry oxygen saturation catheter was inserted into the right jugular bulb to continuously monitor the SjvO2 value. To estimate the rSO2 state, a spectrophotometer probe was attached to the mid-forehead. SjvO2 and rSO2 values were then collected simultaneously using a computer. RESULTS: Neither the cerebral desaturation time (duration during SjvO2 value below 50%), nor the ratio of the cerebral desaturation time to the total CPB time significantly differed (normothermic group: 18+/-6 min, 15+/-6%; hypothermic group: 17+/-6 min, 13+/-6%, respectively). The rSO2 value in the normothermic group decreased during the CPB period compared with the pre-CPB period. The rSO2 value in the hypothermic group did not change throughout the perioperative period. CONCLUSIONS: These findings suggest that near infrared spectroscopy might be sensitive enough to detect subtle changes in regional cerebral oxygenation.     

Pharmacokinetics of doxacurium during normothermic and hypothermic cardiopulmonary bypass surgery

Purpose

To compare the pharmacokinetic behaviour of doxacurium in patients undergoing normothermic or hypothermic cardiopulmonary bypass (CPB) for coronary artery bypass graft surgery.

Methods

Twenty patients in two equal groups were studied. Anaesthesia was induced with sufentanil and midazolam after a standard premedication. Doxacurium was administered at 3 × ED₉₅ (80μ·kg^?1), and anaesthesia was maintained with 0.5 μg·kg^?1 hr^?1 sufentanil, 0.05 mg·kg^?1 midazolam and isoflurane 0.5–1%. Systemic temperature for patients in the normothermic and hypothermic groups was maintained at 33–36C and 26–30C respectively. Timed blood and urine samples were collected and pharmacokinetic parameters were estimated using a non-compartmental approach.

Results

For the normothermic and hypothermie groups, terminal elimination half-life (t_1/2B) was 100.1 ± 28 and 183.8 ± 60 min (P < 0.05) respectively, elimination half-life during the CPB phase (T_1/2 CPB) 114.5 ± 10 and 183.8 ± 60 min (P < 0.05), mean residence time 108.8 ± 25 and 164.8 ± 34 min (P < 0.05) and apparent volume of distribution at steady state 0.20 ± 0.03 and 0.26 ± 0.04 L·kg^?1 (P < 0.05). Compared with the hypothermie group, the normothermic group had a higher rate of renal clearance (1.40 ± 0.4 vs 0.93 ± 0.3 ml·min^?1·kg^?1;P < 0.05) and a higher value for renal clearance as a percentage of the total clearance (76.2 ± 10 vs 58.3 ± 20%).

Conclusion

The elimination rate of doxacurium during normothermic CPB is faster than that in hypothermic CPB.     

Mucosal tissue oxygenation of the porcine jejunum during normothermic cardiopulmonary bypass

Cardiopulmonary bypass (CPB) has been associated with intestinal tissue hypoxia, but direct measurements of mucosal oxygenation have not been performed. In anaesthetized pigs, jejunal mucosal oxygen tension and microvascular haemoglobin oxygen saturation were measured by a Clark- type electrode and tissue reflectance spectrophotometry. In pigs, normothermic CPB with systemic oxygen transport equivalent to baseline values was performed. In control animals, mucosal oxygen tension and mucosal haemoglobin oxygen saturation were mean 5.01 (SD 1.08) kPa and 38.0 (2.3)%, respectively. CPB was associated with a decrease in mucosal oxygen tension to 2.26 (1.21) kPa, decrease in mucosal microvascular haemoglobin oxygen saturation to 26.0 (3.9)% and appearance of oscillations in mucosal microvascular haemoglobin oxygen saturation. With CPB, arterial lactate concentrations increased from 1.77 (1.37) to 3.52 (1.58) mmol litre-1, but transvisceral lactate and splanchnic venous-arterial carbon dioxide tension gradients remained unchanged. Our results support the concept that CPB is associated with diminished oxygenation of intestinal mucosa that is probably caused by regional redistribution.      

中低温减少体外循环下瓣膜置换术中丙泊酚剂量研究

目的以脑电频谱指数(BIS)为参考,探讨不同温度体外循环(CPB)下行瓣膜置换术患者丙泊酚的合适剂量。方法选择60例ASAⅡ-Ⅲ级择期行瓣膜置换术患者,根据术中最低鼻咽温分为2组:浅低温组(32℃,n=30)和中低温组(28℃,n=30)。术中调整丙泊酚剂量,保持BIS值处于40～60。分别于转机前(T1)、阻断升主动脉前(T2)、阻断升主动脉(T3)、开放升主动脉(T4)和停机后(T5)5个时间点,记录患者BIS值和丙泊酚剂量。结果患者均存活出院。组N患者转机前、停机后丙泊酚剂量分别为(4.6±1.3)mg/kg.hr和(4.3±1.6)mg/kg.hr,组H分别为(4.3±1.3)mg/kg.hr和(4.0±1.5)mg/kg.hr,差异均无统计学意义(P>0.05)。CPB转机开始后2组丙泊酚用量均较转机前明显减少,差异具有统计学意义(组N为2.4±1.2 mg/kg.hr,组H为1.2±0.5mg/kg.hr,P<0.01)。T3时间点中低温组较浅低温组下降明显,差异具有统计学意义(P<0.01)。无1例发生术中知晓现象。结论中低温CPB下行瓣膜置换术时,转机开始后应适量减少丙泊酚剂量。     

Jejunal mucosal perfusion is well maintained during mild hypothermic cardiopulmonary bypass in humans

In the present study, the effects of mild hypothermic (34 degrees C) cardiopulmonary bypass (CPB) on jejunal mucosal perfusion (JMP), gastric tonometry, splanchnic lactate, and oxygen extraction were studied in low-risk cardiac surgical patients (n = 10), anesthetized and managed according to clinical routine. JMP was assessed by endoluminal laser Doppler flowmetry. Patients were studied during seven 10-min measurement periods before, during, and 1 h after the end of CPB. Splanchnic oxygen extraction increased during hypothermia and particularly during rewarming and warm CPB. JMP increased during hypothermia (26%), rewarming (31%), and warm CPB (38%) and was higher 1 h after CPB (42%), compared with pre-CPB control. The gastric-arterial PCO(2) difference was slightly increased (range 0.04-2.26 kPa) during rewarming and warm CPB as well as 1 h after CPB, indicating a mismatch between gastric mucosal oxygen delivery and demand. None of the patients produced lactate during CPB. We conclude that jejunal mucosal perfusion appears well preserved during CPB and moderate (34 degrees C) hypothermia; this finding is in contrast to previous studies showing gastric mucosal hypoperfusion during CPB. Implications: Jejunal mucosal perfusion increases during mild hypothermic cardiopulmonary bypass (CPB). Intestinal laser Doppler flowmetry, gastric tonometry, and measurements of splanchnic lactate extraction could not reveal a local or global splanchnic ischemia during or after CPB. A mismatch between splanchnic oxygen delivery and demand was seen, particularly during rewarming and warm CPB.     

Cerebral blood flow and autoregulation during hypothermic cardiopulmonary bypass

Mean hemispheric cerebral blood flow (CBF) was studied following intravenous or intraarterial administration of xenon-133, in 10 men admitted for coronary artery bypass grafting. Repeated CBF measurements were performed to evaluate autoregulation before, during, and after cardiopulmonary bypass (CPB). During CPB mean CBF remained unchanged compared with the pre-CPB level, without evidence of cerebral hyperemia or impairment of autoregulation. A marked increase in CBF occurred after CPB and was followed by a time-dependent reduction toward the pre-CPB level. The data support the alpha-stat regulation theory but cannot explain the cerebral vasodilation observed after CPB.     

Dynamic evaluation of fluid shifts during normothermic and hypothermic cardiopulmonary bypass in piglets

BACKGROUND: Edema, generalized overhydration and organ dysfunction commonly occur in patients undergoing open-heart surgery using cardiopulmonary bypass (CPB) and induced hypothermia. Activation of inflammatory reactions induced by contact between blood and foreign surfaces are commonly held responsible for the disturbances of fluid balance ("capillary leak syndrome"). We used an online technique to determine fluid shifts between the intravascular and the interstitial space during normothermic and hypothermic CPB. METHODS: Piglets were placed on CPB (fixed pump flow) via thoracotomy in general anesthesia. In the normothermic group (n=7), the core temperature was kept at 38 degrees C prior to and during 2 h on CPB, whereas in the hypothermic group (n=7) temperature was lowered to 28 degrees C during bypass. The CPB circuit was primed with acetated Ringer's solution. The blood level in the CPB circuit reservoir was held constant during bypass. Ringer's solution was added when fluid substitution was needed (falling blood level in the reservoir). In addition to invasive hemodynamic monitoring, fluid input and losses were accurately recorded. Inflammatory mediators or markers were not measured in this study. RESULTS: Cardiac output, s-electrolytes and arterial blood gases were similar in the two groups in the pre-bypass period. At start of CPB the blood level in the machine reservoir fell markedly in both groups, necessitating fluid supplementation and leading to a markedly reduced hematocrit. This extra fluid need was transient in the normothermic group, but persisted in the hypothermic animals. After 2 h of CPB the hypothermic animals had received 7 times more fluid as compared to the normothermic pigs. CONCLUSION: We found strong indications for a greater fluid extravasation during hypothermic CPB compared with normothermic CPB. The experimental model using the CPB-circuit reservoir as a fluid gauge gives us the opportunity to study further fluid volume shifts, its causes and potential ways to optimize fluid therapy protocols.     

Cerebral response to hemodilution during hypothermic cardiopulmonary bypass in adults.

We examined the cerebral response to changing hematocrit during hypothermic cardiopulmonary bypass (CPB) in 18 adults. Cerebral blood flow (CBF), cerebral metabolic rate for oxygen (CMRO2), and cerebral oxygen delivery (CDO2) were determined using the nitrous oxide saturation technique. Measurements were obtained before CPB at 36 degrees C, and twice during 27 degrees C CPB: first with a hemoglobin (Hgb) of 6.2 +/- 1.2 g/dL and then with a Hgb of 8.5 +/- 1.2 g/dL. During hypothermia, appropriate reductions in CMRO2 were demonstrated, but hemodilution-associated increases in CBF offset the reduction in CBF seen with hypothermia. At 27 degrees C CPB, as the Hgb concentration was increased from 6.2 to 8.5 g/ dL, CBF decreased. CDO2 and CMRO2 were no different whether the Hgb was 6.2 or 8.5 g/dL. In eight patients in whom the Hgb was less than 6 g/dL, CDO2 remained more than twice CMRO2. IMPLICATIONS: This study suggests that cerebral oxygen balance during cardiopulmonary bypass is well maintained at more pronounced levels of hemodilution than are typically practiced, because changes in cerebral blood flow compensate for changes in hemoglobin concentration.     

Hemodynamic and hormonal responses to hypothermic and normothermic cardiopulmonary bypass.

Normothermic cardiopulmonary bypass (CPB) is used in cardiac surgery at some institutions. To compare hemodynamic and hormonal responses to hypothermic (29 degrees C) and normothermic nonpulsatile CPB, 20 adults undergoing coronary artery bypass graft and/or aortic valve replacement were studied. Hemodynamic measurements and plasma hormone concentrations were obtained from preinduction to the third postoperative hour. The two groups were given similar amounts of anesthetics and vasodilators. Systemic vascular resistance increased only during hypothermic CPB, and heart rate was higher at the end of hypothermic CPB. Postoperative central venous pressure and pulmonary capillary wedge pressure were lower after hypothermic CPB. Oxygen consumption decreased by 45% during hypothermic CPB, did not change during normothermic CPB, but increased similarly in the two groups after surgery; mixed venous oxygen saturation (SvO2) was significantly lower during normothermic CPB. Urine output and composition were similar in the two groups. In both groups, plasma epinephrine, norepinephrine, renin activity, and arginine vasopressin concentrations increased during and after CPB. However, epinephrine, norepinephrine, and dopamine were 200%, 202%, and 165% higher during normothermic CPB than during hypothermic CPB, respectively. Dopamine and prolactin increased significantly during normothermic but not hypothermic CPB. Atrial natriuretic peptide increased at the end of CPB and total thyroxine decreased during and after CPB, with no difference between groups. This study suggests that higher systemic vascular resistance during hypothermic CPB is not caused by hormonal changes, but might be caused by other factors such as greater blood viscosity. A higher perfusion index during normothermic CPB might have allowed higher SvO2.     

Effects of perfusion pressure on cerebral blood flow and oxygenation during normothermic cardiopulmonary bypass

BACKGROUND: Central nervous system dysfunction after cardiopulmonary bypass (CPB) is an important cause of morbidity and mortality after cardiac surgery. Perfusion pressure (PP) during CPB could be one of the important determinants of cerebral blood flow (CBF). The objective of the present study was to determine the effect of PP on CBF and cerebral oxgenation during normothermic CPB. METHODS: Twelve adult patients undergoing coronary artery bypass graft surgery were randomly assigned to one of two groups based on PP (High and Low group). Patients in High group received phenylephrine immediately after the onset of CPB to maintain PP between 60 and 80 mmHg. Oxyhemoglobin (O2Hb), deoxyhemoglobin (HHb), tissue oxygenation index (TOI), and oxidized cytochrome aa3 (CtOx) were measured by near-infrared spectroscopy, and internal jugular venous bulb blood oxygen saturation (SjvO2) was measured simultaneously. S-100 beta protein concentrations were also measured before and after CPB. RESULTS: SjvO2 in High group increased significantly during CPB. CtOx in Low group decreased significantly during CPB, whereas TOI was unchanged. Although S-100 beta increased significantly at the end of CPB, there was no difference between the groups. CONCLUSIONS: These results suggest that maintaining high PP is benefical for CBF during normothermic CPB.     

Performance evaluation of a new pulse oximeter during mild hypothermic cardiopulmonary bypass

Newly developed pulse oximeters (POs) are designed to display accurate SpO(2) during motion and hypoperfusion. We compared the performance of a new PO, the Masimo SET Radical (M), with a conventional PO, the Nihon Kohden AY-900P (N), during hypothermic cardiopulmonary bypass. Eighteen patients were studied prospectively. PO failure was defined as failure to show no SpO(2) value or show incorrect SpO(2) values for longer than 3 min continuously. PO failure occurred in 4 and 14 patients with M and N, respectively (P = 0.0022). All 4 patients in whom PO failure developed with M were among the 14 patients with N. No SpO(2) was provided for 4% +/- 12% of the duration of aorta cross-clamping with M and 36% +/- 39% with N (P = 0.002). Skin temperature and mean arterial blood pressure when PO failure started to occur and ended were similar between M and N. PO failure easily developed in patients with preoperative diuretic therapy or with intraoperative hyperlactatemia in N, but not in M. M was able to display accurate SpO(2) values significantly more frequently and longer than N during mild hypothermic cardiopulmonary bypass with nonpulsatile flow, suggesting that M is more useful for monitoring SpO(2) during hypoperfusion. IMPLICATIONS: We compared the performance of a new pulse oximeter with that of a conventional pulse oximeter during hypothermic cardiopulmonary bypass with nonpulsatile flow. The newly developed device displayed accurate SpO(2) significantly more frequently and longer than a conventional oximeter. Newly developed pulse oximeters seem to be more useful for monitoring SpO(2) during hypoperfusion.     

Cerebral oxygenation during non-blood prime cardiopulmonary bypass in congenital heart surgery

To analyze oxygen delivery to the brain and cerebral cellular oxygenation during non-blood prime and blood prime cardiopulmonary bypass (CPB), 22 patients undergoing cardiac surgery with CPB were studied by near infrared spectroscopy (NIRS) monitor (NIRO 500, Hamamatsu Photonics). NIRS can assess continuously cytochrome oxidase (Cyt.aa 3) which is the terminal enzyme of the intramitochondrial respiratory chain. Patients were grouped according to conditions of CPB management: one group underwent repair with non-blood prime (group A, n = 12); the second group underwent with blood prime (group B, n = 10). Body weights ranged from 5.5 kg to 58 kg in group A, and 2.9 kg to 16 kg respectively. CPB was maintained at flow rates between 100 to 150 ml/kg/min. and the acid-base management strategy was alpha stat in all patients. No neurological complication was observed. NIRS date were expressed as changes from baseline where cannulation was prepared. The lowest value of Cyt.aa 3 was -2.7 +/- 0.7 mumol/l in the group A, and -3.9 +/- 1.0 mumol/l in the group B. From the standpoint of changes in Cyt.aa 3, non-blood prime cases we studied were speculated to be within a safety limit. In order to define the definite safety limits, however, further studies including the reduction velocity of Cyt.aa 3 signal as well as the absolute value of the lowest Cyt.aa 3 concentration are required.     

The effects of normothermic versus hypothermic cardiopulmonary bypass on hepatic blood flow

Canadian Journal of Anesthesia/Journal canadien d'anesthésie -     

Blood/gas solubility coefficient and blood concentration of enflurane during normothermic and hypothermic cardiopulmonary bypass

The blood/gas solubility coefficient and blood concentration of enflurane were measured at intervals in 10 patients undergoing coronary artery revascularization with cardiopulmonary bypass (CPB) and moderate hypothermia. A constant end-tidal concentration of enflurane was maintained throughout the study. Blood/gas solubility coefficient was determined at 37 degrees C, which when combined with an initial single-step equilibration of the blood sample with air, permitted the accurate measurement of blood concentration. Blood/gas solubility coefficient and blood concentration both decreased significantly with the onset of CPB. During the period of hypothermia, blood/gas solubility as measured at 37 degrees C showed little change; however, there was a progressive, marked increase in blood concentration with a mean increase of 80% prior to rewarming. Therefore, the level of anesthesia provided by enflurane may lighten with the onset of CPB, and a deeper level will accompany any decrease in blood temperature. On rewarming, blood concentration levels rapidly returned to levels similar to those measured before cooling. The increased uptake and accumulation of volatile anesthetic agent that occurred as a result of the period of hypothermic CPB was rapidly cleared. The rapidity with which blood concentration responded to the changes occurring during CPB make it unlikely that there was any significant increase in myocardial depression in response to the raised blood concentration secondary to the hypothermia.