THE purpose of this review is to evaluate recent developments in our understanding of the inflammatory response to cardiac surgery. Scientific knowledge in this field is continually expanding, potentially significant advances are regularly reported, and this area constitutes a major interface of clinical and basic scientific research. The review is divided into four major sections. The first section describes the pathophysiology of the inflammatory response to cardiac surgery. Factors that influence the extent of the inflammatory response, including the immunomodulatory effects of drugs commonly administered perioperatively, are discussed in the second section. The third section examines the evidence that the inflammatory response contributes to adverse perioperative events, in particular organ dysfunction, while the final section evaluates potential therapeutic strategies to control this response. The review concludes with a summary of potential future research directions and key deficiencies in our knowledge regarding the inflammatory response to cardiac surgery.

The systemic inflammatory response to cardiac surgery: implications for the anesthesiologist.

Oxygen Carriers (“Blood Substitutes”)Raison d'Etre, Chemistry, and Some Physiology Blut ist ein ganz besondrer Saft1

https://www.thelancet.com/pdfs/journals/lancet/PIIS0140-6736(08)60837-5.pdf

Induced hypothermia and fever control for prevention and treatment of neurological injuries

This review analyzes, in some depth, results of studies on the effect of lowered temperatures on cerebral energy metabolism in animals under normal conditions and in some selected pathologic situations. In sedated and paralyzed mammals, acute uncomplicated 0.5- to 3-h hypothermia decreases the global cerebral metabolic rate for glucose (CMR(glc)) and oxygen (CMRo(2)) but maintains a slightly better energy level, which indicates that ATP breakdown is reduced more than its synthesis. Intracellular alkalinization stimulates glycolysis and independently enhances energy generation. Lowering of temperature during hypoxia-ischemia slows the rate of glucose, phosphocreatine, and ATP breakdown and lactate and inorganic phosphate formation, and improves recovery of energetic parameters during reperfusion. Mild hypothermia of 12 to 24-h duration after normothermic hypoxic-ischemic insults seems to prevent or ameliorate secondary failures in energy parameters. The authors conclude that lowered head temperatures help to protect and maintain normal CNS function by preserving brain ATP supply and level. Hypothermia may thus prove a promising avenue in the treatment of stroke and trauma and, in particular, of perinatal brain injury.

Effects of hypothermia on energy metabolism in Mammalian central nervous system.

Carbon Dioxide and the Cerebral Circulation

BACKGROUND Jugular venous hemoglobin desaturation during the rewarming phase of cardiopulmonary bypass is associated with adverse neuropsychologic outcome and may indicate a pathologic mismatch between cerebral blood flow (CBF) and cerebral metabolic rate for oxygen (CMRO2). In some studies, rapid rewarming from hypothermic cardiopulmonary bypass results in greater jugular venous hemoglobin desaturation. The authors wished to determine if rewarming rate influences the temperature dependence of CBF and CMRO2. METHODS Anesthetized New Zealand white rabbits, cooled to 25 degrees C on cardiopulmonary bypass, were randomized to one of two rewarming groups. In the fast group (n = 9), aortic blood temperature was made normothermic within 4 min. In the slow group (n = 9), aortic blood temperature was made normothermic over 25 min. Cerebral blood flow (microspheres) and CMRO2 (Fick) were determined at baseline (25 degrees C), and at brain temperatures of 28 degrees, 31 degrees, 34 degrees, and 37 degrees C during rewarming. RESULTS Systemic physiologic variables appeared similar between groups. At a brain temperature of 28 degrees C, CMRO2 was 47% greater in the fast rewarming group than in the slow group (2.2 +/- 0.5 vs. 1.5 +/- 0.2 ml O2.100 g-1. min-1, respectively; P = 0.01), whereas CBF did not differ (48 +/- 18 vs. 49 +/- 8 ml.100 g-1.min-1, respectively; P = 0.47). Throughout rewarming, CBF increased as a function of brain temperature but was indistinguishable between groups. Cerebral metabolic rate for oxygen differences between groups decreased as brain temperatures increased. CONCLUSIONS Cerebral venous hemoglobin desaturation with rapid rewarming is caused by an increase in CMRO2 that is temporarily greater than the increase in CBF. This mismatch may indicate a transient abnormality in flow-metabolism coupling, or the effect of temperature gradients on oxygen transfer from hemoglobin to brain.

/pdf/rapid-rewarming-causes-an-increase-in-the-cerebral-metabolic-19jljysfs4.pdf

Rapid rewarming causes an increase in the cerebral metabolic rate for oxygen that is temporarily unmatched by cerebral blood flow. A study during cardiopulmonary bypass in rabbits.

Background. Possible utility of high-dose i.v. melatonin as an anaesthetic adjuvant has not been studied. This study compared its effects with thiopental and propofol. Methods. Sprague Dawley rats were assigned to receive bolus or cumulative i.v. doses of melatonin, thiopental or propofol. Righting reflex, hindpaw withdrawal to a noxious stimulus, response to tail clamping and haemodynamic effects were assessed. Results. Melatonin caused a dose-dependent increase in paw withdrawal threshold and the percent of rats displaying loss of the righting reflex. Melatonin was comparable to thiopental and propofol in terms of its rapid onset of hypnosis. The mean ED50 values for loss of righting reflex were 5.4 (sem 1.2), 12.5 (1.1) and 178 (1.1) mg kg–1 for propofol, thiopental and melatonin, respectively. The percent of rats displaying loss of response to tail clamping was greater with propofol than with melatonin (P Conclusion. I.V. melatonin can exert hypnotic effects similar to those observed with thiopental and propofol. Melatonin exhibited significant antinociceptive effects but was less effective in abolishing the response to tail clamping. Br J Anaesth 2003; 90: 504–7

Pharmacological effects of intravenous melatonin: comparative studies with thiopental and propofol

Moderate hemodilution (hematocrit approximately 30%) reduces neurologic injury after focal cerebral ischemia. In contrast, both clinical and experimental studies suggest that marked hemodilution (hematocrit < 30%) may exacerbate neurologic injury. We compared the effect of marked versus minimal hemodilution on cerebral infarct volume after focal cerebral ischemia in rabbits. Anesthetized New Zealand White rabbits underwent hemodilution by exchange of arterial blood with 6% high molecular weight hydroxyethyl starch. In the marked hemodilution group (n = 15) the target hemoglobin concentration was 6 g/100 mL. In the minimal hemodilution group (n = 15) the target hemoglobin concentration was 11 g/100 mL. After hemodilution, middle cerebral artery occlusion was achieved by embolizing an autologous blood clot via the internal carotid artery. Four hours after embolization, the animals were killed and their brains removed. Brains were sectioned, stained with 2,3,5-triphenyltetrazolium chloride, and infarct volumes determined via quantitative image analysis. Systemic physiologic variables were similar between groups, except for arterial hemoglobin concentration. The percentage of hemispheric infarct was significantly larger in the marked hemodilution group as compared to the minimal hemodilution group, 70% +/- 19% vs 51% +/- 23%, respectively (mean +/- SD); P = 0.02. Similarly, the percentage of infarct was greater in the hemodilution group as compared to the minimal hemodilution group in both cortex (73% +/- 18% vs 54% +/- 23%, respectively; P = 0.02) and subcortex (62% +/- 25% vs 44% +/- 23%, respectively; P = 0.04). These findings indicate that marked hemodilution exacerbates neurologic injury resulting from permanent focal ischemia. Although some degree of hemodilution may improve neurologic outcome, the advantage is lost at an extreme level of therapy.

Marked hemodilution increases neurologic injury after focal cerebral ischemia in rabbits.

BACKGROUND Greater cerebral metabolic suppression may increase the brain's tolerance to ischemia. Previous studies examining the magnitude of metabolic suppression afforded by profound hypothermia suggest that the greater arterial carbon dioxide tension of pH-stat management may increase metabolic suppression when compared with alpha-stat management. METHODS New Zealand White rabbits, anesthetized with fentanyl and diazepam, were maintained during cardiopulmonary bypass (CPB) at a brain temperature of 17 degrees C with alpha-stat (group A, n = 9) or pH-stat (group B, n = 9) management. Measurements of brain temperature, systemic hemodynamics, arterial and cerebral venous blood gases and oxygen content, cerebral blood flow (CBF) (radiolabeled microspheres), and cerebral metabolic rate for oxygen (CMRO2) (Fick) were made in each animal at 65 and 95 min of CPB. To control for arterial pressure and CBF differences between techniques, additional rabbits underwent CPB at 17 degrees C. In group C (alpha-stat, n = 8), arterial pressure was decreased with nitroglycerin to values observed with pH-stat management. In group D (pH-stat, n = 8), arterial pressure was increased with angiotensin II to values observed with alpha-stat management. In groups C and D, CBF and CMRO2 were determined before (65 min of CPB) and after (95 min of CPB) arterial pressure manipulation. RESULTS In groups A (alpha-stat) and B (pH-stat), arterial pressure; hemispheric CBF (44 +/- 17 vs. 21 +/- 4 ml.100 g-1.min-1 [median +/- quartile deviation]; P = 0.017); and CMRO2 (0.54 +/- 0.13 vs. 0.32 +/- 0.10 ml O2 x 100 g-1.min-1; P = 0.0015) were greater in alpha-stat than in pH-stat animals, respectively. As a result of arterial pressure manipulation, in groups C (alpha-stat) and D (pH-stat) neither arterial pressure (75 +/- 2 vs. 78 +/- 2 mmHg) nor hemispheric CBF (40 +/- 10 vs. 48 +/- 6 ml.100 g-1.min-1; P = 0.21) differed between alpha-stat and pH-stat management, respectively. Nevertheless, CMRO2 was greater in alpha-stat than in pH-stat animals (0.71 +/- 0.10 vs. 0.45 +/- 0.10 ml O2 x 100g-1.min-1, respectively; P = 0.002). CONCLUSIONS At 17 degrees C, CMRO2 with pH-stat management is 35-40% less than that with alpha-stat management and is independent of CBF or arterial pressure differences between the techniques.

pH-stat management reduces the cerebral metabolic rate for oxygen during profound hypothermia (17 degrees C). A study during cardiopulmonary bypass in rabbits.

BACKGROUND It is unclear whether nonpulsatile perfusion adversely affects the brain. This study compared cerebral blood flow (CBF) and cerebral metabolic rate for oxygen (CMRO2) betwen pulsatile and nonpulsatile cardiopulmonary bypass (CPB) in rabbits at 27 degrees C. METHODS In experiment A, 24 anesthetized New Zealand white rabbits underwent pulsatile CPB at 27 degrees C, using alpha-stat acid-base management. Animals were randomized to three groups based upon the duration of the period of systolic ejection (100, 120, 140 ms) and were perfused for 20 min at each of three pulse rates (150, 200, 250 pulse/min), generating nine arterial pressure waveforms. Arterial pressure waveform, arterial and cerebral venous oxygen content, CBF (radiolabeled microspheres), and CMRO2 (Fick) were measured at the end of each 20-min period. In experiment B, 16 anesthetized rabbits were randomized to pulsatile (120-ms ejection period, 250 pulse/min) or nonpulsatile CPB at 27 degrees C. AFter 1 h, arterial pressure waveform, arterial and cerebral venous oxygen content, CBF and CMRO2 were measured. RESULTS In experiment A, CBF and CMRO2 were independent of ejection period and pulse rate. Thus, all nine waveforms were physiologically equivalent. In experiment B, CBF did not differ between pulsatile and nonpulsatile bypass, 30 +/- 4 versus 32 +/- 5 ml.100 g-1.min-1, respectively. CMRO2 did not differ between pulsatile and nonpulsatile bypass, 1.7 +/- 0.2 versus 1.6 +/- 0.2 ml.100 g-1.min-1, respectively. CONCLUSIONS During CPB in rabbits at 27 degrees C, neither CBF nor CMRO2 is affected by flow character.

Johann Cutkomp

Papers

Rapid rewarming causes an increase in the cerebral metabolic rate for oxygen that is temporarily unmatched by cerebral blood flow. A study during cardiopulmonary bypass in rabbits.

Pharmacological effects of intravenous melatonin: comparative studies with thiopental and propofol

Marked hemodilution increases neurologic injury after focal cerebral ischemia in rabbits.

pH-stat management reduces the cerebral metabolic rate for oxygen during profound hypothermia (17 degrees C). A study during cardiopulmonary bypass in rabbits.

Pulsatile Versus Nonpulsatile Cardiopulmonary BypassNo Difference in Brain Blood Flow or Metabolism at 27°C