Effects Of Hypothermic Cardiopulmonary Bypass Research Articles

Abstract PR283

Background & Objectives: The objective of this study was to evaluate the effect of hypothermic cardiopulmonary bypass (CPB) on cerebral oxygen saturation (rSO2), internal jugular bulb venous oxygen saturation (SjvO2), mixed venous oxygen saturation (SvO2), and bispectral index (BIS) used to monitor cerebral oxygen balance in pediatric patients. Materials & Methods: Sixty American Society of Anesthesiologists Class II-III patients aged 1 to 4 years old with congenital heart disease scheduled for elective cardiac surgery were included in this study. Temperature, BIS, rSO2, mean arterial pressure, central venous pressure, cerebral perfusion pressure (CPP), and hematocrit were recorded. Internal jugular bulb venous oxygen saturation and SvO2 were obtained from blood gas analysis at the time points: after induction of anesthesia (T0), beginning of CPB (T1), ascending aortic occlusion (T2), 20 minutes after initiating CPB (T3), coronary reperfusion (T4), separation from CPB (T5), and at the end of operation (T6). The effect of hypothermia or changes in CPP on rSO2, SjvO2, SvO2, and BIS were analyzed. Results: Compared with postinduction baseline values, rSO2 significantly decreased at all-time points: onset of extracorporeal circulation, ascending aortic occlusion, 20 minutes after CPB initiation, coronary reperfusion, and separation from CPB (P<0.05). Compared with measurements made following induction of anesthesia, SjvO2 significantly increased with initiation of CPB, ascending aortic occlusion, 20 minutes after initiating CPB, coronary reperfusion, and separation from CPB (P<0.05). Compared with induction of anesthesia, BIS significantly decreased with the onset of CPB, aortic cross clamping, 20 minutes after initiating CPB, and coronary reperfusion (P<0.05). Bispectral index increased following separation from CPB. There was no significant change in SvO2 during cardiopulmonary bypass (P > 0.05). Correlation analysis demonstrated that rSO2 was positively related to CPP (r =0.687, P=0.000), with a low linear correlation to temperature (r=0.453, P=0.000). Internal jugular bulb venous oxygen saturation was negatively related to temperature (r=-0.689, P=0.000). Bispectral index was positively related to both temperature (r=0.824, P=0.000) and CPP (r=0.782, P=0.000). Cerebral oxygen saturation had a positive linear correlation with CPP and a low linear correlation to temperature. Internal jugular bulb venous oxygen saturation had a negative linear correlation to temperature. Conclusion: Pre-and and early postbypass periods are vulnerable times for adequate cerebral oxygenation. Anesthetic management must aim to optimize the supply and demand relationship Disclosure of Interest: None declared

Effects of hypothermic cardiopulmonary bypass on rocuronium-induced neuromuscular blockade in patients undergoing open heart surgery

Objective To evaluate the effects of hypothermic cardiopulmonary bypass (CPB) on rocuronium-induced neuromuscular blockade in the patients undergoing open heart surgery.Methods Twenty ASA physical status Ⅰ or Ⅱ patients,scheduled for elective open heart surgery,aged 18-45 yr,with body mass index of 18-25 kg/m2,were randomly assigned into 2 groups (n =10 each) using a random number table:room temperature group (group R) and hypothermia group (group H).The nasopharyngeal temperature was maintained at 30-31 ℃ during CPB in group H or at 36-37 ℃ during CPB in group R,and it was maintained at 36-37 ℃ before and after CPB in both groups.Anesthesia was induced with iv etomidate 0.3 mg/kg,fentanyl 2-4 μg/kg and rocuronium 0.3 mg/kg.The patients were tracheally intubated and mechanically ventilated.Anesthesia was maintained with iv infusion of sufentanil and intermittent iv boluses of midazolam and fentanyl.BIS value was maintained at 40-60.Neuromuscular block was monitored using TOF-WATCH SX accelerometer.Train-of-four stimulation (intensity 40 mA,frequency 2 Hz,wave length 0.2 ms,interval 12 s) of ulnar nerve was used.Rocuronium was infused intravenously using an automatic feedback control system to maintain T1 at 8％-12％.At 10 min after start of operation (T0),10 min after onset of CPB (T1),and 10 min after termination of CPB,blood samples were collected for determination of the plasma concentration of rocuronium (by HPLC).The infusion rate and consumption of rocuronium were recorded before,during and after CPB.Results Compared with group R,the plasma concentration of rocuronium was significantly decreased at T1,2,and the infusion rate and consumption of rocuronium were decreased before and after CPB in group H.Conclusion Hypothermic CPB enhances rocuroniuminduced neuromuscular blockade in the patients undergoing open heart surgery. Key words: Hypothermia, induced; Cardiopulmonary bypass ; Androstanols ; Neuromuscular blockade

Cisatracurium pharmacokinetics and pharmacodynamics during hypothermic cardiopulmonary bypass in infants and children

Hypothermia potentiates neuromuscular blockade in adults during cardiopulmonary bypass (CPB) but the pediatric literature is sparse. Temperature-dependent Hoffman degradation of cisatracurium may allow reduction in infusion rate (IR) during hypothermia. The effect of hypothermic CPB on the pharmacokinetics (PK) and pharmacodynamics (PD) of cisatracurium has not been described in children. Using neuromuscular monitoring with a Datex Relaxograph, cisatracurium IR was adjusted to obtain a pseudo-steady state during each phase of surgery (pre-CPB, CPB, post-CPB). Paired samples were taken at each phase. Cisatracurium plasma concentrations (Cpss) were determined by HPLC. Core and skin temperatures were recorded. Data from ten infants were analyzed: Group 1: mean 33.6°C; Group 2: mean 21.9°C. To maintain T1% between 5% and 10% in Group 2, the IR was decreased by a mean of 89% (P < 0.001). IR was not significantly different in Group 1. Post-CPB IR approximated pre-CPB rates in both groups. During CPB, Cpss fell by 27% in Group 1 and by 50% in Group 2 (P = 0.039). Post-CPB Cpss was not significantly different to pre-CPB in either group. Clearance did not change significantly in Group 1 but fell significantly in Group 2 during CPB (P = 0.002). Clearance post-CPB was unchanged from pre-CPB. Cisatracurium IR may be decreased by around 60% during CPB with moderate hypothermia but can be maintained at baseline during mild hypothermia.

Propofol requirement titrated to bispectral index: a comparison between hypothermic and normothermic cardiopulmonary bypass

Though propofol requirement is expected to decrease during cardiopulmonary bypass (CPB), a few studies have failed to demonstrate this. The factors affecting pharmacokinetics of propofol and, therefore, the requirement, are different during hypothermic and normothermic CPB. We evaluated and compared the requirement of propofol during hypothermic and normothermic CPB. Fifty adult patients scheduled for elective cardiac surgery on CPB were recruited and randomly allocated into hypothermic CPB (28-30 degrees C) (Group H) and normothermic CPB (35-37 degrees C) (Group N) groups. Patients were induced and maintained with propofol titrated to maintain a target bispectral index (BIS) of 50 +/- 10. Propofol requirement (mean +/- SD) was similar in normothermic and hypothermic groups, both before CPB (4.9 +/- 1.5 mg kg(-1)hr(-1) in Group N, 4.6 +/- 1.5 mg kg(-1)hr(-1) in Group H) and after cessation of bypass (p > 0.05) (4.6 +/- 1.8 mg kg(-1)hr(-1) in Group N and 4.3 +/- 1.7 mg kg(-1)hr(-1) in Group H). CPB significantly reduced (p < 0.001) propofol requirements in both arms of the study (Group N: 2.9 +/- 1.4 mg kg(-1)hr(-1)and Group H: 1.3 +/- 0.7 mg kg(-1)hr(-1)). This reduction was more pronounced in the hypothermic group (p < 0.001). The BIS (median +/- inter quartile range) remained constant during normothermic CPB (50 +/- 8.8), but declined significantly during hypothermic CPB (41 +/- 5.6) despite decreased usage of propofol during hypothermia. No patient had recall of intra-operative events. CPB decreases the magnitude of propofol requirements and the effect of hypothermic CPB is significantly more than that of normothermic CPB.

Brain Injury in Congenital Heart Disease

Mortality rates for virtually all forms of congenital heart disease have declined with dramatic advances in medical, transcatheter, and surgical therapies. 1 As the population of congenital heart disease survivors has burgeoned, however, their long-term functional morbidities have become the focus of increasing concern. Among the foremost morbidities are adverse neurodevelopmental outcomes, with their profound personal and societal costs. 2 Article p 280 Neurological and developmental outcomes of congenital heart patients are influenced by many factors, both innate and acquired, with cumulative effects. Genetic syndromes such as trisomy 21 or 22q11 microdeletion3–5 may affect both the heart and the brain. Cerebral dysgenesis is reported to occur in 10% to 29% of children with congenital heart disease in autopsy series, with the incidence varying by lesion 6–8 ; findings may range from microdysgenesis to gross abnormalities such as agenesis of the corpus callosum, incomplete operculization, and microcephaly. During fetal life, congenital heart lesions may be associated with changes in cerebrovascular blood flow distribution and resistance. For example, fetuses with hypoplastic left heart syndrome, whose cerebral perfusion is supplied retrograde through the ductus arteriosus, have lower cerebrovascular resistance than normal. 9 Postnatal neurodevelopmental risk factors may derive from the sequelae of congenital heart disease itself—eg, chronic severe hypoxemia, failure to thrive, arrhythmias with cardiac arrest or hypotension—or from the procedures used for cardiac correction or palliation.10 Neuropathological studies have revealed both focal and diffuse infarction. Focal infarction has been ascribed to thromboembolic events, whereas a diffuse pattern of cerebral injury has been attributed to hypotension and hypoperfusion.11 More recent neuropathological data in infants who underwent reparative or palliative cardiac surgery reveals that not only are these children at increased risk of gray matter injury but also nascent white matter is at risk. For instance, in a series of infants who died after cardiac surgery, cerebral white matter damage (periventricular leukomalacia or diffuse white matter gliosis) was the most significant lesion in terms of severity and incidence. 12 Similarly, MRI performed in patients with congenital heart disease after surgery has revealed findings consistent with both gray matter injury and widely distributed white matter injury. 13 Risk factors for brain injury during infant heart surgery have been particularly well studied. Cardiopulmonary bypass carries the risks of particulate and gaseous microemboli, macroemboli, and hypoperfusion with accompanying diffuse ischemia/reperfusion injury. In neonates and infants undergoing surgery with use of hypothermic bypass techniques, the risk of brain injury may be influenced by perfusion variables such as the duration of total circulation arrest,14 the depth of hypothermia, 15 the rate and duration of core cooling, 16 pH management during core cooling (alpha-stat versus pH stat), 17,18 and the level of hemodilution. 19 Disruption of cerebral vasoregulation in the early postoperative period renders the brain more vulnerable to hemodynamic instability. 20–22 After infant heart surgery, longer length of stay in the intensive care unit or hospital is associated with worse neurodevelopmental outcome on mid-term follow-up. 23,24

Effect of Hypothermic Cardiopulmonary Bypass on Blood Viscoelasticity in Pediatric Cardiac Patients

The objective of this study was to determine the changes in blood viscoelasticity during and after pediatric cardiopulmonary bypass (CPB) procedures. Twelve pediatric cardiac patients, subjected to hypothermic (22-28 degrees C) CPB procedures were enrolled in this study. Viscosity and elasticity were measured at strains of 0.2, 1.0, and 5.0 using a Vilastic-3 Viscoelasticity Analyzer. Arterial blood samples (1 ml each) were taken before CPB, on normothermic CPB, hypothermic CPB, and 1 and 24 hours after CPB. Compared with the pre-CPB levels (0.0464 +/- 0.007 Poise), viscosity at a strain of 1.0 was significantly lower during normothermic CPB (0.0305 +/- 0.006 Poise, p < 0.01), hypothermic CPB (0.03 +/- 0.0007 Poise, p < 0.01), and 1 hour after CPB (0.0334 +/- 0.006 Poise, p < 0.01). Viscosity at a strain of 1.0 24 hours after CPB (0.0525 +/- 0.01 Poise, p = NS) was slightly higher than pre-CPB levels. Elasticity at a strain of 1.0 was significantly altered during normothermic CPB (0.0016 +/- 0.0007 Poise, p < 0.01), hypothermic CPB (0.0015 +/- 0.0007 Poise, p < 0.01), and 1 hour after CPB (0.0017 +/- 0.0005 Poise, p < 0.01) compared to the pre-CPB levels (0.0048 +/- 0.0001 Poise). Elasticity at a strain of 1.0 24 hours after CPB (0.0068 +/- 0.003 Poise, p = 0.06) was significantly higher compared to the pre-CPB level (0.0048 +/- 0.0001 Poise). Viscoelasticity at strains of 0.2 and 5.0 had patterns similar to those seen with a strain of 1.0. Viscosity and elasticity at strains of 0.2, 1.0, and 5.0 were significantly altered during normothermic and hypothermic CPB and 1 hour after CPB. Viscoelasticity of blood was slightly higher 24 hours after CPB at all strains. Further investigation of the effects of hypothermic CPB on blood viscoelasticity and the outcomes of pediatric cardiac patients are warranted.

The effects of hypothermic cardiopulmonary bypass on Doppler cerebral blood flow during the first 24 postoperative hours

To provide understanding of influence of cardiopulmonary bypass (CPB) on cerebral blood flow (CBF), we investigated the effect of CPB on patients' cerebral haemodynamic parameters. Twenty-three patients were prospectively enrolled. CBF was estimated by transcranial Doppler (TCD) to measure blood velocity in the middle cerebral artery (MVMCA), preoperatively T(0) and at four postoperative times (T(1), T(2), T(3), T(4)). At times T(2), T(3) and T(4), MVMCA remained at higher levels than T(0) (P < 0.05). In the multivariate analysis PaCO(2) was independently associated to MVMCA at times T(1) and T(2) (P = 0.03, P = 0.01, respectively) and temperature was independently associated with MVMCA at time T(1) (P = 0.02). Thus, the present study showed an increase in CBF after CPB, that was correlated with raised temperature but not with decrease in haematocrit.

Temperature Management During Cardiopulmonary Bypass: Effect of Rewarming Rate on Cognitive Dysfunction

Hypothermia is a very strong neuroprotective agent during cerebral ischemia. However, several randomized clinical trials have failed to demonstrate a protective effect of hypothermic cardiopulmonary bypass on postoperative cognitive deficits. The lack of neuroprotection may be due to rapid rewarming, which in turn may result in cerebral hyperthermia. The purpose of this study was to detennine if rapid rewarming at the end of cardiopulmonary bypass is associated with an increased risk of postoperative neuropsychologic impairment. Methods: A battery of neuropsychologic tests were administered preand postoperatively to patients undergoing elective coronary bypass surgery. Patients were allowed to drift to 34°C then rewarmed to 37.5°C at the end of cardiopulmonary bypass. Patients were divided into 2 groups according to the median time to rewarm (21 minutes): a rapid group (n = 70) and a slow group (n = 76). Results: The 2 groups of patients were similar for all pre-, intra-, and postoperative variables, with the exception of rewarming times (15 ± 4 minutes [mean ± SD]) in the rapid group versus 30 ± 9 minutes in the slow group, p &lt; 0.001). The rapid group had a significantly higher prevalence of neuropsychologic impairment 1 week postoperatively than the slow group (82% versus 57%, p &lt; 0.05), as well as worse mean scores on all neuropsychologic tests. There was a nonsignificant trend toward increased neuropsychologic impairment 3 months postoperatively in the rapid group, as well as worse mean scores on 8 of the 10 tests. Conclusions: Rapid rewarming at the end of cardiopulmonary bypass may increase the risk of postoperative cognitive impairment. Until further studies are performed, rapid rewarming should be avoided in order to minimize the risk of cerebral hyperthermia.

Effects of Hypothermic Cardiopulmonary Bypass on Bispectral Analysis

Background: Patient awareness is a particular problem in cardiac anesthesia with cardiopulmonary bypass (CPB). Transformed electroencephalogram monitors, such as the Bispectral index (BIS) monitor, has been advocated as a tool that may reduce the incidence of unexpected intraoperative recall. The authors studied the effects of hypothermia during CPB on the BIS score and the BIS can be a useful monitor to measure anesthetic depth and requirement during hypothermic CPB. Methods: Eighteen consenting volunteers scheduled for an elective cardiac surgery were studied. Volunteers were randomly allocated to one of two groups. All patients were given propofol by a target controlled infusion system, Diprifusor, with fentanyl (0.6 /kg/min). In group A, before and during CPB propofol was infused at a predetermined target plasma concentration (2.0 /ml), the BIS score and temperature were monitored. In group B, before and during CPB, to maintain the BIS score at 30-40 units, changing propofol plasma concentrations and temperature were monitored. Then we asked patients about intraoperative awareness. Results: In group A, compared with before the start of CPB, the BIS score was decreased by the temperature (P

Guías de práctica clínica de la Sociedad Española de Cardiología en el postoperado de cardiopatía congénita

Improvements in myocardial protection, surgical techniques, and perioperative care have made it possible to achieve better prognosis in most congenital heart defects. This requires a coordinated, multidisciplinary approach to patient care, based on the preservation of adequate oxygen delivery to vital organs. It is important to have an understanding of normal postoperative status after cardiac surgery so that abnormal postoperative convalescence can be identified and treated.The causes of abnormal convalescence may be grouped into three categories: a) the pathophysiology of the defect before surgery and the acute changes in physiology that result from surgery; b) the effects of hypothermic cardiopulmonary bypass and deep hypothermic circulatory arrest on organ function, and c) the presence of residual anatomic defects. These conditions may result in prolonged convalescence as well as increased morbidity and mortality. Three primary hemodynamic pathophysiologic disturbances may occur during the postoperative period and lead to abnormal convalescence: left ventricular dysfunction, right ventricular dysfunction and pulmonary hypertension. Though sometimes not directly related to either the cardiac defect or surgery, specific problems involving different organs may alter the normal postoperative period. Neurologic, pneumologic, renal, gastrointestinal and infective complications are discussed separately.

The Effect of Hypothermic Cardiopulmonary Bypass on Gastric Mucosal pH

The Effect of Hypothermic Cardiopulmonary Bypass on Gastric Mucosal pH

The Effect of Hypothermic Cardiopulmonary Bypass on Plasma Adrenomedullin in Adult Cardiac Surgical Patients

Cardiopulmonary bypass (CPB) can evoke a systemic inflammatory response, which is accompanied by an increase in plasma cytokines that may stimulate the production of adrenomedullin (AM), a potent vasodilator peptide.This study was undertaken to investigate whether CPB influenced plasma AM concentration in 10 patients undergoing cardiac surgical procedures. We found that the plasma AM concentration increased significantly after the commencement of CPB, with the greatest increase observed at weaning from bypass (P < 0.01). After CPB, plasma AM concentration declined but still exceeded baseline significantly 24 h postoperatively. The increase in the plasma AM concentration at weaning from CPB correlated significantly with aortic cross-clamp time (r = 0.74, P < 0.05). The authors conclude that the secretion of AM into circulation is augmented by CPB in patients undergoing cardiac surgery, which suggests a possible role of AM in cardiovascular regulation during and after surgery with CPB. (Anesth Analg 1997;84:1193-7)

Effects of Hypothermic Cardiopulmonary Bypass on the Pharmacodynamic of Rocuronium

Effects of Hypothermic Cardiopulmonary Bypass on the Pharmacodynamic of Rocuronium

Adhesion Molecules and Inflammation

Adhesion Molecules and Inflammation

Effects of hypothermic cardiopulmonary bypass on the pharmacodynamics and pharmacokinetics of rocuronium

To study the influence of hypothermic cardiopulmonary bypass (CPB) on the pharmacodynamics and pharmacokinetics of rocuronium. Prospective, descriptive study. Operating room at a university hospital. Ten ASA class III and IV patients, ranging in age from 35 to 75 years, scheduled for elective coronary artery bypass grafting. Neuromuscular transmission was monitored mechanomyographically. The time course of action of maintenance doses and plasma concentration-response relationships were determined before, during, and after CPB. The plasma concentration decay and renal elimination were studied simultaneously. Plasma and urine concentration of rocuronium were determined by high-performance liquid chromatography. Hypothermic CPB prolonged the duration of action of maintenance doses and coincided with a lower plasma concentration at a twitch response of 5% of control. The duration of action of maintenance doses returned to prehypothermic CPB level after rewarming to a nasopharyngeal temperature of 37 degrees C. The plasma concentration-response relationship did not return to precooling control value, probably owing to persisting peripheral hypothermia. Both the renal elimination of rocuronium and the plasma concentration decay after the last maintenance dose under normothermic conditions resembled values obtained in patients not undergoing hypothermic CPB. Hypothermic CPB prolongs the duration of action of maintenance doses and alters the plasma concentration-response relationship of rocuronium. These changes may be the result of, on the one hand, an increased sensitivity of the neuromuscular transmission and/or decreased muscle contractility and, on the other hand, the result of a reduced plasma clearance during hypothermia.

Effects of hypothermic cardiopulmonary bypass on sympathetic nerve activity

Effects of hypothermic cardiopulmonary bypass on sympathetic nerve activity

The effect of hypothermic cardiopulmonary bypass and total circulatory arrest on cerebral metabolism in neonates, infants, and children

Cardiopulmonary bypass management in neonates, infants, and children often requires the use of deep hypothermia at 18 degrees C with occasional periods of circulatory arrest and represents marked physiologic extremes of temperature and perfusion. The safety of these techniques is largely dependent on the reduction of metabolism, particularly cerebral metabolism. We studied the effect of hypothermia on cerebral metabolism during cardiac surgery and quantified the changes. Cerebral metabolism was measured before, during, and after hypothermic cardiopulmonary bypass in 46 pediatric patients, aged 1 day to 14 years. Patients were grouped on the basis of the different bypass techniques commonly used in children: group A--moderate hypothermic bypass at 28 degrees C; group B--deep hypothermic bypass at 18 degrees to 20 degrees C with maintenance of continuous flow; and group C--deep hypothermic circulatory arrest at 18 degrees C. Cerebral metabolism significantly decreased under hypothermic conditions in all groups compared with control levels at normothermia, the data demonstrating an exponential relationship between temperature and cerebral metabolism and an average temperature coefficient of 3.65. There was no significant difference in the rate of metabolism reduction (temperature coefficient) in patients cooled to 28 degrees and 18 degrees C. From these data we were able to derive an equation that numerically expresses a hypothermic metabolic index, which quantitates duration of brain protection provided by reduction of cerebral metabolism owing to hypothermic bypass over any temperature range. Based on this index, patients cooled to 28 degrees C have a predicted ischemic tolerance of 11 to 19 minutes. The predicted duration that the brain can tolerate ischemia ("safe" period of deep hypothermic circulatory arrest) in patients cooled to 18 degrees C, based on our metabolic index, is 39 to 65 minutes, similar to the safe period of deep hypothermic circulatory arrest known to be tolerated clinically. In groups A and B (no circulatory arrest), cerebral metabolism returned to control in the rewarming phase of bypass and after bypass. In group C (circulatory arrest), cerebral metabolism and oxygen extraction remained significantly reduced during rewarming and after bypass, suggesting disordered cerebral metabolism and oxygen utilization after deep hypothermic circulatory arrest. The results of this study suggest that cerebral metabolism is exponentially related to temperature during hypothermic bypass with a temperature coefficient of 3.65 in neonates infants and children. Deep hypothermic circulatory arrest changes cerebral metabolism and blood flow after the arrest period despite adequate hypothermic suppression of metabolism.

Metabolism of the heart and brain during hypothermic cardiopulmonary bypass

The alterations in tissue metabolism induced by hypothermic cardiopulmonary bypass are not completely known. Phosphorus-31 nuclear magnetic resonance spectroscopy was used to determine the effect of hypothermic cardiopulmonary bypass on energy states and intracellular pH of the heart and brain. Sheep were instrumented for cardiopulmonary bypass and had a radiofrequency coil placed over either the heart or skull. The animals were placed in a 4.7-T magnet at 37 °C and spectra obtained. The animals were cooled on cardiopulmonary bypass to either 26 °C (n = 17) or 18 °C (n = 14) for brain studies and to 26 °C (n = 12) for heart studies. Hypothermia increased the phosphocreatine/adenosine triphosphate ratio in the heart (2.38 ± 0.23 versus 3.18 ±0.37, 37 ° versus 26 °C, respectively, p = 0.03). The brain phosphocreatine/adenosine triphosphate ratio increased from 1.70 ± 0.09 at 37 °C to 2.00 ± 0.12 at 26 °C ( p = 0.009) and 2.10 ± 0.07 at 18 °C ( p = 0.0001). Intracellular pH increased during hypothermia (heart: 7.05 ± 0.02 to 7.18 ± 0.02, 37 ° versus 26 °C, p = 0.0001; and brain: 7.07 ± 0.02 versus 7.32 ± 0.02, 37 ° versus 18 °C, p = 0.0001). The adenosine triphosphate resonance position is known to be sensitive to magnesium binding as well as temperature and was shifted upfield ( p < 0.01) in both the heart and brain. This effect could be totally explained by the temperature dependence of this process. It is concluded that deep hypothermia increases the energy state and the intracellular pH of both the heart and the brain. The elevated intracellular pH and the increase in tissue energy state may partially explain the beneficial effects of hypothermia on organ tolerance to ischemia.

Cerebral autoregulation during deep hypothermic nonpulsatile cardiopulmonary bypass with selective cerebral perfusion in dogs

We evaluated effects of hypothermic cardiopulmonary bypass on the cerebral circulation and metabolism of six dogs over a temperature range of 37 degrees to 20 degrees C under alphastat acid-base regulation (uncorrected for body temperature). Cerebral metabolic rate for oxygen was determined from the difference between arterial and sagittal sinus blood oxygen contents, and direct cerebral blood flow measurements of the venous outflow from the isolated sagittal sinus. After core cooling at a constant perfusion flow rate of 80 ml/kg/min, cerebral blood flow significantly reduced to 10.0 +/- 1.1 ml/100 gm/min at 20 degrees C (20% +/- 2% of that at 37 degrees C) because of an increase in the cerebral vascular resistance (339% +/- 48%). Cerebral metabolic rate for oxygen reduced to 18% +/- 2%. The upper body vascular resistance decreased to a greater extent than the lower body resistance (37% +/- 4% versus 82% +/- 12%). In the selective cerebral perfusion system at 20 degrees C, when perfusion pressure (mean carotid arterial pressure minus central venous pressure) was lowered from 90 mm Hg by graded reduction of the perfusion flow rate, cerebral blood flow remained constant down to a perfusion pressure of 40 mm Hg, then steeply declined. Cerebral metabolic rate for oxygen also kept a constant level down to 30 mm Hg, then fell abruptly. Definite autoregulatory response was detected even in profound hypothermic nonpulsatile cardiopulmonary bypass. These results suggest that cerebral perfusion flow should be regulated so as to keep the perfusion pressure within the range of cerebral autoregulation to prevent cerebral ischemia or hyperperfusion, especially during selective cerebral perfusion for operations on the aortic arch.

Effect of Hypothermic Cardiopulmonary Bypass on Nitroprusside Metabolism

At a rectal temperature of 25° C, six patients undergoing hypothermic cardiopulmonary bypass received intravenous infusions of sodium nitroprusside (SNP) at a rate of 7.3 ±1.7 μg/kg/min for 20 minutes. Total SNP dose per patient was 11.0 ± 1.1 mg. Blood samples for serum cyanide (CN−), red blood cell cyanide (RBC CN−), and thiocyanate (SCN−) determinations were drawn immediately before SNP infusion. These determinations were repeated at the end of the infusion, at the start of rewarming, and at a rectal temperature >34° C and 1, 4 (five subjects), and 24 hours (three subjects) thereafter. Extracorporeal blood flow was held constant at 2.4 L/min/m2 and mean arterial pressure was maintained between 50 to 100 mm Hg with phenylephrine (3.62 ± 0.75 mg) during SNP infusion and trimethaphan (37.8 ± 15.6 mg) after the end of the infusion. There was a significant increase in RBC CN− after the SNP infusion that lasted until the subjects were rewarmed. One subject developed a peak RBC CN− level of 0.8 μg/ml. Plasma CN− levels changed little throughout and SCN− levels were elevated only after rewarming. The nonenzymatic release of free CN− from SNP was not inhibited by hypothermia, while the enzymatic detoxification of CN− to SCN− may have been delayed. Clinical Pharmacology and Therapeutics (1985) 37, 680–683; doi:10.1038/clpt.1985.111