Differential responses of cerebral and renal oxygenation to altered perfusion conditions during experimental cardiopulmonary bypass in sheep.

We tested whether the brain and kidney respond differently to cardiopulmonary bypass (CPB) and to changes in perfusion conditions during CPB. Therefore, in ovine CPB, we assessed regional cerebral oxygen saturation (rSO2 ) by near-infrared spectroscopy and renal cortical and medullary tissue oxygen tension (PO2 ), and, in some protocols, brain tissue PO2 , by phosphorescence lifetime oximetry. During CPB, rSO2 correlated with mixed venous SO2 (r = 0.78) and brain tissue PO2 (r = 0.49) when arterial PO2 was varied. During the first 30 min of CPB, brain tissue PO2 , rSO2 and renal cortical tissue PO2 did not fall, but renal medullary tissue PO2 did. Nevertheless, compared with stable anaesthesia, during stable CPB, rSO2 (66.8 decreasing to 61.3%) and both renal cortical (90.8 decreasing to 43.5 mm Hg) and medullary (44.3 decreasing to 19.2 mm Hg) tissue PO2 were lower. Both rSO2 and renal PO2 increased when pump flow was increased from 60 to 100 mL kg-1 min-1 at a target arterial pressure of 70 mm Hg. They also both increased when pump flow and arterial pressure were increased simultaneously. Neither was significantly altered by partially pulsatile flow. The vasopressor, metaraminol, dose-dependently decreased rSO2 , but increased renal cortical and medullary PO2 . Increasing blood haemoglobin concentration increased rSO2 , but not renal PO2 . We conclude that both the brain and kidney are susceptible to hypoxia during CPB, which can be alleviated by increasing pump flow, even without increasing arterial pressure. However, increasing blood haemoglobin concentration increases brain, but not kidney oxygenation, whereas vasopressor support with metaraminol increases kidney, but not brain oxygenation.

Effects of furosemide, acetazolamide and amiloride on renal cortical and medullary tissue oxygenation in non-anaesthetised healthy sheep.

It has been proposed that diuretics can improve renal tissue oxygenation through inhibition of tubular sodium reabsorption and reduced metabolic demand. However, the impact of clinically used diuretic drugs on the renal cortical and medullary microcirculation is unclear. Therefore, we examined the effects of three commonly used diuretics, at clinically relevant doses, on renal cortical and medullary perfusion and oxygenation in non-anaesthetised healthy sheep. Merino ewes received acetazolamide (250 mg; n = 9), furosemide (20 mg; n = 10) or amiloride (10 mg; n = 7) intravenously. Systemic and renal haemodynamics, renal cortical and medullary tissue perfusion and P O 2 ${P_{{{\mathrm{O}}_{\mathrm{2}}}}}$ , and renal function were then monitored for up to 8 h post-treatment. The peak diuretic response occurred 2 h (99.4 ± 14.8 mL/h) after acetazolamide, at which stage cortical and medullary tissue perfusion and P O 2 ${P_{{{\mathrm{O}}_{\mathrm{2}}}}}$ were not significantly different from their baseline levels. The peak diuretic response to furosemide occurred at 1 h (196.5 ± 12.3 mL/h) post-treatment but there were no significant changes in cortical and medullary tissue oxygenation during this period. However, cortical tissue P O 2 ${P_{{{\mathrm{O}}_{\mathrm{2}}}}}$ fell from 40.1 ± 3.8 mmHg at baseline to 17.2 ± 4.4 mmHg at 3 h and to 20.5 ± 5.3 mmHg at 6 h after furosemide administration. Amiloride did not produce a diuretic response and was not associated with significant changes in cortical or medullary tissue oxygenation. In conclusion, clinically relevant doses of diuretic agents did not improve regional renal tissue oxygenation in healthy animals during the 8 h experimentation period. On the contrary, rebound renal cortical hypoxia may develop after dissipation of furosemide-induced diuresis.

Dynamic responses of renal oxygenation at the onset of cardiopulmonary bypass in sheep and man.

INTRODUCTION: The renal medulla is susceptible to hypoxia during cardiopulmonary bypass (CPB), which may contribute to the development of acute kidney injury. But the speed of onset of renal medullary hypoxia remains unknown. METHODS: We continuously measured renal medullary oxygen tension (MPO2) in 24 sheep, and urinary PO2 (UPO2) as an index of MPO2 in 92 patients, before and after induction of CPB. RESULTS: In laterally recumbent sheep with a right thoracotomy (n = 20), even before CPB commenced MPO2 fell from (mean ± SEM) 52 ± 4 to 41 ±5 mmHg simultaneously with reduced arterial pressure (from 108 ± 5 to 88 ± 5 mmHg). In dorsally recumbent sheep with a medial sternotomy (n = 4), MPO2 was even more severely reduced (to 12 ± 12 mmHg) before CPB. In laterally recumbent sheep in which a crystalloid prime was used (n = 7), after commencing CPB, MPO2 fell abruptly to 24 ±6 mmHg within 20-30 minutes. MPO2 during CPB was not improved by adding donor blood to the prime (n = 13). In patients undergoing cardiac surgery, UPO2 fell by 4 ± 1 mmHg and mean arterial pressure fell by 7 ± 1 mmHg during the 30 minutes before CPB. UPO2 then fell by a further 12 ± 2 mmHg during the first 30 minutes of CPB but remained relatively stable for the remaining 24 minutes of observation. CONCLUSIONS: Renal medullary hypoxia is an early event during CPB. It starts to develop even before CPB, presumably due to a pressure-dependent decrease in renal blood flow. Medullary hypoxia during CPB appears to be promoted by hypotension and is not ameliorated by increasing blood hemoglobin concentration.

Influence of blood haemoglobin concentration on renal haemodynamics and oxygenation during experimental cardiopulmonary bypass in sheep.

AIM: Blood transfusion may improve renal oxygenation during cardiopulmonary bypass (CPB). In an ovine model of experimental CPB, we tested whether increasing blood haemoglobin concentration [Hb] from ~7 g dL-1 to ~9 g dL-1 improves renal tissue oxygenation. METHODS: Ten sheep were studied while conscious, under stable isoflurane anaesthesia, and during 3 hours of CPB. In a randomized cross-over design, 5 sheep commenced bypass at a high target [Hb], achieved by adding 600 mL donor blood to the priming solution. After 90 minutes of CPB, PlasmaLyte® was added to the blood reservoir to achieve low target [Hb]. For the other 5 sheep, no blood was added to the prime, but after 90 minutes of CPB, 800-900 mL of donor blood was given to achieve a high target [Hb]. RESULTS: Overall, CPB was associated with marked reductions in renal oxygen delivery (-50 ± 12%, mean ± 95% confidence interval) and medullary tissue oxygen tension (PO2 , -54 ± 29%). Renal fractional oxygen extraction was 17 ± 10% less during CPB at high [Hb] than low [Hb] (P = .04). Nevertheless, no increase in tissue PO2 in either the renal medulla (0 ± 6 mmHg change, P > .99) or cortex (-19 ± 13 mmHg change, P = .08) was detected with high [Hb]. CONCLUSIONS: In experimental CPB blood transfusion to increase Hb concentration from ~7 g dL-1 to ~9 g dL-1 did not improve renal cortical or medullary tissue PO2 even though it decreased whole kidney oxygen extraction.

Effects of heparin bridging anticoagulation on perioperative bleeding and thromboembolic risks in patients undergoing abdominal malignancy surgery.

Recent publications provided controversial results indicating that perioperative heparin bridging anticoagulation (HBA) increased the bleeding risk without decreasing the thromboembolic risk in patients undergoing minor surgery. To investigate if this is also the case in high-risk patients undergoing major abdominal malignancy surgery, we retrospectively collected data of 3268 patients over a 10-year period. After the interruption of preoperative antithrombotic agents, HBA was initiated with a prophylactic-dose of unfractionated heparin in 133 patients (HBA group), and 62 patients did not receive HBA (non-HBA group). The incidence of exogenous blood transfusion (EBT) and thromboembolic events (TEEs) within 30 days after surgery were compared between the HBA and non-HBA groups. The results showed that the incidence of EBT and TEEs was similar between the two groups (23.3 vs 19.4 %; P = 0.535) and (4.1 vs 3.2 %; P = 0.821), respectively. The amount of intraoperative bleeding and the length of postoperative hospital stay were also similar [median (quantile 1-3); 192 (71-498) vs 228 ml (100-685); P = 0.422] and [12 (9-19) vs 14.5 days (10-21); P = 0.052], respectively. These findings may suggest it is unlikely that prophylactic-dose HBA affects bleeding and thromboembolic risks in patients undergoing major abdominal malignancy surgery.

[Thrombotic and Bleeding Risks of Patients on Antiplatelet Therapy Undergoing Major Abdominal Malignancy Surgery].

BACKGROUND: Controversies still exist whether to continue or withdraw aspirin (ASA) perioperatively. This study was performed to determine whether patients on preoperative antiplatelet therapy (APT) benefit from continuing ASA in terms of thrombotic and bleeding risk prevention. METHODS: Among 307 consecutive patients who were on APT preoperatively for the secondary prevention of cardiovascular disease and who underwent elective major abdominal malignancy surgery, 148 patients had all the preoperative APT withdrawn and the remaining 159 patients continued only ASA. Comparisons were made between the 2 groups regarding the rate and the amount of exogenous blood transfusion as well as the incidence of thromboembolic events (TEEs) within 1 month after surgery. RESULTS: The incidence of perioperative TEEs of the APT withdrawn group was significantly higher than that of the ASA group (6.2% vs 0%, P = 0.005), while the rate and the amount of exogenous blood transfusion were not different each other (23.6% vs 17.0%, P = 0.146 and 4 units vs 4 units, P = 0.544, respectively). CONCLUSIONS: Considering the relatively low bleeding risk when continued and the increased thrombotic risk after withdrawal, ASA should be continued perioperatively in patients undergoing major abdominal malignancy surgery.