Sympathoadrenal function during cardiac operations in infants with the technique of surface cooling, limited cardiopulmonary bypass, and circulatory arrest

The sympathoadrenal response to surface cooling, limited cardiopulmonary bypass, and deep hypothermic circulatory arrest was investigated in 22 infants undergoing correction of congenital heart defects. Surface cooling to 26 degrees C was associated with a significant rise in plasma epinephrine and norepinephrine levels. Both levels fell during the period of core cooling on bypass, presumably because of hemodilution. Following the period of circulatory arrest there was a rise in both catecholamine levels that correlated nonlinearly with the duration of circulatory arrest. The catecholamine levels remained high after rewarming until the chest was closed. The results suggest that this type of surgical procedure produces severe sympathoadrenal stress. The extremely high values found in the postarrest period in some patients, who had had a long period of arrest (greater than 40 minutes), may indicate hypoxic stress. The biological effect of high circulating plasma catecholamines during hypothermia is difficult to assess. The heart rate response to plasma catecholamine levels tended to diminish on cooling in our patients.     

Rewarming from moderate to deep hypothermia: plasma catecholamine content, metabolism and circulatory function. 2 case reports

Two patients were rewarmed from hypothermia (esophageal temperature 27.2 degrees C, 27.5 degrees C respectively). The first case suffered from head-injury after alcohol ingestion and was deeply comatose. A metabolic or cardiovascular regulatory response to cold was not observed in this patient. The relationship between esophageal temperature and whole-body-oxygen consumption was quantified with a Q10 of 2.75 during rewarming (27.2-37.2 degrees C). His epinephrine levels were greatly elevated to 1,000 pg/ml whereas norepinephrine levels were only moderately increased to 250 pg/ml. Premature ventricular contractions (PVCs) during intubation or from the pulmonary artery catheter were not observed. The second patient was a 87 year old man with accidental hypothermia. He exhibited shivering at an esophageal temperature of 27.5 degrees C which indicated persistent thermoregulation. In contrast to the first case his norepinephrine levels were elevated to 1,500 pg/ml and his epinephrine levels only to 450 pg/ml. After onset of surface rewarming an additional increase in norepinephrine levels was observed and an increasing rate of PVC's (15/min) recorded, which ceased when temperature returned to normal. Our observations indicate that part of the cardiac complications during rewarming from deep hypothermia may result from thermoregulation and additional catecholamine liberation.     

Deep hypothermia and total circulatory arrest: The effect of method of cooling on the catecholamine response to arrest

Deep hypothermia and total circulatory arrest are used in the treatment of cardiac surgical patients in early infancy. These techniques produce a massive rise in serum norepinepherine and epinephrine levels. The effect of method of cooling on this response was investigated in 15 infant lambs during the first 2 weeks of life, mean age 4.8 days, mean weight 4.7 kg. Three groups were investigated—one in which continued cardiopulmonary bypass at 100 cc/kg and cooling and rewarming alone were employed; one in which core cooling, 1 hr of circulatory arrest, and warming were employed; and one in which surface cooling from 37 to 28°C then core cooling <18°C, arrest for 60 min, and rewarming to 37°C were employed. Temperature gradients between thermister sites in the brain, heart, nasopharyngeal, rectal, and peripheral muscle and blood samples for norepinephrine, epinephrine, and arterial pH measurements were obtained at 37°C control, <18°C preintervention, <18°C postintervention, 37°C postcontrol. Changes between pre- and post-intervention in each group and postcontrol values were elevated as well as gradients between thermistor sites. Results revealed no significant difference in arterial or venous pH in any group during the intervention period; elevation in muscle temperature and muscle-to-core temperature gradient in both the core-cooled groups; significant elevations in norepinepherine and epinepherine (P < 0.001) in the arrested compared to the nonarrested groups; and significant elevations in the norepinephrine (P < 0.05) in the surface/core from the core-arrested group. Postcontrol values for norepinephrine and epinephrine remained significantly elevated in both total circulatory arrest (P < 0.001, P < 0.02) with norepinephrine in the surface/core group significantly elevated (P < 0.05) over the core group. Results confirm that with deep hypothermia and total circulatory arrest a massive rise in norepinephrine and epinephrine occurs. Greater eveness of cooling results from a surface/core technique. In this group higher elevations in norepinephrine are demonstrated to be consistent with better cooling of the peripheral muscle bed, a biochemical marker of peripheral cooling and arrest. With rewarming significant elevations of both norepinephrine and epinephrine remain in both total circulatory arrest groups, while in the surface/core group norepinephrine levels remained significantly elevated over the core group. These findings are consistent with the gradients of cooling which exist in the surface/core group and reflect greater norepinephrine response from peripheral sources which persist in the postoperative period in these animals.     

Effects of pulsatile perfusion on plasma catecholamine levels and hemodynamics during and after cardiac operations with cardiopulmonary bypass

Thirty patients scheduled for elective coronary artery bypass grafting were studied in two groups. Group A had standard cardiopulmonary bypass with nonpulsatile perfusion and group B had pulsatile perfusion. Measurements of plasma epinephrine, norepinephrine, granulocyte elastase, and hemodynamic parameters including mean arterial pressure total peripheral resistance, cardiac index, and pulmonary capillary wedge pressure were made before and after anesthesia induction, after surgical incision, during cardiopulmonary bypass, and 2, 4, and 24 hours after the operation. The venous compliance of the total body venous bed was measured at the end of the operation. In all patients the total net fluid balance was determined during bypass and in the postoperative period. In both groups plasma catecholamine levels increased 5 minutes after institution of bypass (epinephrine 176 +/- 56 to 611 +/- 108 pg/ml and norepinephrine 231 +/- 48 to 518 +/- 100 pg/ml in group A; epinephrine 168 +/- 40 to 444 +/- 100 pg/ml and norepinephrine 162 +/- 44 to 267 +/- 52 pg/ml in group B). The maximum catecholamine level was measured between the end of bypass and 2 hours after the end of bypass (epinephrine 1489 +/- 169 pg/ml and norepinephrine 1542 +/- 108 pg/ml in group A; epinephrine 990 +/- 134 pg/ml and norepinephrine 934 +/- 197 pg/ml in group B). During the same period mean arterial pressure and total peripheral resistance were also significantly higher in group A than in group B mean arterial pressure, 61.4 +/- 3 versus 53.6 +/- 3, p less than 0.06; total peripheral resistance, 1055 +/- 60 versus 899 +/- 45, p less than 0.01). The venous compliance was significantly higher in group A than in group B (2.4 +/- 0.3 versus 1.2 +/- 0.3 ml/mm Hg/kg body weight). The intraoperative and perioperative net fluid balance were significantly higher in group A than in group B (p less than 0.005). The average postoperative tracheal intubation time was also significantly longer in group A than in group B (4.6 +/- 1.2 hours versus 2.7 +/- 0.8 hours, p less than 0.001). No significant difference was detected in either hemoglobin or plasma free hemoglobin content between the two groups postoperatively. The results suggest that pulsatile perfusion, when compared with nonpulsatile perfusion, can attenuate the catecholamine stress response to cardiopulmonary bypass, reduce the fluid overloading of patients, and improve the postoperative recovery period as evaluated by tracheal intubation time.     

Effect of hypothermic hemodilutional cardiopulmonary bypass on plasma sufentanil and catecholamine concentrations in humans

The effect of hypothermic hemodilutional cardiopulmonary bypass (CPB) on plasma sufentanil and catecholamine concentrations was studied in four groups of ten patients each, receiving four different doses of sufentanil. Samples for measurement of sufentanil were obtained before CPB, at 15, 30, and 45 minutes of CPB, during rewarming, immediately after and 15, 60, and 240 minutes after CPB. In addition, in groups III and IV, which received the highest dose of sufentanil, blood samples were also obtained for measurement of plasma levels of epinephrine and norepinephrine. Sufentanil concentration decreased in all groups with the start of CPB (group I, 2.92 +/- 0.2 to 2.04 +/- 0.2; group II, 3.30 +/- 0.3 to 1.51 +/- 0.2; group III, 7.08 +/- 0.7 to 3.45 +/- 0.3; group IV, 10.33 +/- 0.5 to 4.59 +/- 0.5 ng/ml). No further decreases occurred during CPB but increases occurred with rewarming. The first measurement after CPB approached the concentration before CPB (group I, 2.82 +/- 0.3; group II, 2.56 +/- 0.5; group III, 4.42 +/- 0.4; group IV, 6.10 +/- 0.4 ng/ml). Norepinephrine concentrations demonstrated a wide variability with no significant changes. Epinephrine levels increased significantly during rewarming in both groups (group III, 141 +/- 23 to 279 +/- 79 pg/ml; P less than 0.05; group IV, 105 +/- 24 to 267 +/- 68 pg/ml, P less than 0.05). The stability of plasma sufentanil concentrations during CPB suggest that no measurable metabolism or excretion occurred. The increase with rewarming and after CPB suggest significant sequestration.(ABSTRACT TRUNCATED AT 250 WORDS)     

Elevated plasma vasopressin (AVP) levels during resection of pheochromocytomas

During the evaluation of epidural blockade with light general anesthesia for pheochromocytoma resection, increases in plasma arginine vasopressin (AVP) concentrations were noted. We measured AVP levels in conjunction with plasma catecholamines during perioperative maneuvers in eight consecutive patients undergoing resection of pheochromocytomas. Hormonal responses (mean +/- SE) for preoperative baseline and peak values during tumor manipulation were as follows: AVP, 5 microgram/ml or picogram/ml (+/- 1.7) to a peak of 129 pg/ml (+/- 44) pg/ml; norepinephrine, 5,834 pg/ml (+/- 2,564) to 72,422 (+/- 31,433) pg/ml; epinephrine, 1,033 pg/ml (+/- 405) to 56,444 (+/- 23,542) pg/ml; and dopamine, 165 pg/ml (+/- 35) to 4,231 (+/- 1,318) pg/ml. Maximal AVP values occurred with tumor manipulation and remained elevated for 24 hours postoperatively. Neither epidural placement, induction of anesthesia, nor epidural narcotics used for postoperative pain control had any effect on AVP or catecholamine levels. These extraordinarily high concentrations of plasma AVP found during tumor manipulation may contribute to hemodynamic lability and fluid problems in patients undergoing surgery for the treatment of pheochromocytoma.     

The role of catecholamines in the pathogenesis of neurogenic pulmonary edema associated with subarachnoid hemorrhage

Background

Neurogenic pulmonary edema (NPE) occurs frequently after aneurysmal subarachnoid hemorrhage (SAH), and excessive release of catecholamines (epinephrine/norepinephrine) has been suggested as its principal cause. The objective of this retrospective study is to evaluate the relative contribution of each catecholamine in the pathogenesis of NPE associated with SAH.

Methods

Records of 63 SAH patients (20 men/43 women) whose plasma catecholamine levels were measured within 48?h of SAH onset were reviewed, and the clinical characteristics and laboratory data of those who developed early-onset NPE were analyzed thoroughly.

Results

Seven patients (11?%) were diagnosed with NPE on admission. Demographic comparison revealed that the NPE+ group sustained more severe SAH than the NPE? group. Cardiac dysfunction was also significantly more profound in the former, and the great majority of the NPE+ group sustained concomitant cardiac wall motion abnormality. There was no significant difference in the plasma epinephrine levels between NPE+ and NPE? group (324.6?±?172.8 vs 163.1?±?257.2?pg/ml, p?=?0.11). By contrast, plasma norepinephrine levels were significantly higher in the NPE+ group (2977.6?±?2034.5 vs 847.9?±?535.6?pg/ml, p?<?0.001). Multivariate regression analysis revealed that increased norepinephrine levels were associated with NPE (OR, 1.003; 95?% CI, 1.002–1.007). Plasma epinephrine and norepinephrine levels were positively correlated (R?=?0.48, p?<?0.001). According to receiver operating characteristic curve analysis, the threshold value for plasma norepinephrine predictive of NPE was 2,000?pg/ml, with an area under the curve value of 0.85.

Conclusions

Elevated plasma norepinephrine may have more active role in the pathogenesis of SAH-induced NPE compared with epinephrine, although both catecholamines may be involved via multiple signaling pathways.     

Cerebral metabolism during deep hypothermic circulatory arrest vs moderate hypothermic selective cerebral perfusion in a piglet model: a microdialysis study

Background: Few data exist regarding antegrade selective cerebral perfusion (ASCP) and its application in newborn and juvenile patients. Clinical data suggest ASCP alone to be superior to deep hypothermic circulatory arrest (DHCA); however, the effects of moderate hypothermia during ASCP on cerebral metabolism in this patient population are still unclear. Methods: After obtaining the approval from animal investigation committee, 16 piglets were randomly assigned to circulatory arrest combined with either ASCP at 27°C or DHCA at 18°C for 90 min. Cerebral oxygen extraction fraction (COEF) from blood as well as cerebral tissue glucose, glycerol, lactate, pyruvate, and the lactate/pyruvate ratio (L/P ratio) by microdialysis were obtained repeatedly. Results: COEF was lower during cooling and rewarming, respectively, in the DHCA18 group compared to the ASCP27 group (30 ± 8 vs 56 ± 13% and 35 ± 6 vs 58 ± 7%, respectively). Glucose decreased in both the DHCA18 and ASCP27 groups during the course of cardiopulmonary bypass (CPB), but were higher in the ASCP27 group during ASCP, compared to the DHCA18 group during circulatory arrest (0.7 ± 0.1 vs 0.2 ± 0.1 mm ·l^?1, P < 0.05). Pyruvate was higher (ASCP27 vs DHCA18: 53 ± 17 vs 6 ± 2 μm ·l^?1, P < 0.05), and the L/P ratio increased during circulatory arrest in the DHCA18 group, compared to the selective perfusion phase of the ASCP27 group (DHCA18 vs ASCP27: 1891 ± 1020 vs 70 ± 28, P < 0.01). Conclusions: In this piglet model, both cerebral oxygenation and microdialysis findings suggested a depletion of cerebral energy stores during circulatory arrest in the DHCA18 group, compared to selective cerebral perfusion combined with circulatory arrest in the ASCP27 group.     

Physiologic effects of deep hypothermia and microwave rewarming: possible application for neonatal cardiac surgery

Deep hypothermia (20 C) without cardiopulmonary bypass is a valuable technique during cardiac surgery in infants but rewarming of the heart following circulatory arrest and cardiac repair has traditionally been a lengthy and difficult process. In experimental animals rewarming the heart with microwave energy, as reported in this work, warms the heart before warming the periphery. In 18 mongrel dogs that were surface cooled to 20 C, we found that during microwave rewarming the core temperature rose 4.7 C per hour. Whole body oxygen consumption, heart rate, and cardiac output returned to normal at rates equal to the rates at which they decreased during surface cooling. Blood pressure and arterial gases remained adequate. Microwave rewarming appears to be a useful method for reestablishment of cardiac function and normothermia following deep hypothermia.     

The effects of deep hypothermic cardiopulmonary bypass and total circulatory arrest on cerebral blood flow in infants and children

Cardiopulmonary bypass management in infants and children involves extensive alterations in temperature, hemodilution, and perfusion pressure, with occasional periods of circulatory arrest. Despite the use of these biologic extremes of temperature and perfusion, their effects on cerebral blood flow are unknown. This study was designed to examine the relationship of mean arterial pressure and nasopharyngeal temperature to cerebral blood flow during deep hypothermic cardiopulmonary bypass (18 degrees to 22 degrees C) with and without periods of total circulatory arrest. Cerebral blood flow was measured before, during, and after deep hypothermic cardiopulmonary bypass using xenon clearance techniques in 25 children, aged 2 days to 60 months. Fourteen patients underwent repair with circulatory arrest. There was a highly significant correlation of cerebral blood flow with temperature during cardiopulmonary bypass (p = 0.007). During deep hypothermic bypass there was a significant association between cerebral blood flow and mean arterial pressure (p = 0.027). In infants undergoing repair with deep hypothermia alone, cerebral blood flow returned to prebypass levels in the rewarming phase of bypass. However, in patients undergoing repair with circulatory arrest, no significant increase in cerebral blood flow during rewarming or even after bypass was observed (p = 0.01). These data show that deep hypothermic cardiopulmonary bypass significantly decreases cerebral blood flow because of temperature reduction. Under conditions of deep hypothermia, cerebral pressure-flow autoregulation is lost. This study also demonstrates that cerebral reperfusion after deep hypothermia is impaired if the patient is exposed to a period of total circulatory arrest.     

Studies of lipid and carbohydrate metabolism during surface-induced deep hypothermia with circulatory arrest for open-heart surgery

Plasma lipids, blood glucose, plasma insulin (IRI) and serum dopamine-β-hydroxylase (DBH) were measured in 30 subjects undergoing surface-induced deep hypothermia with circulatory arrest for open-heart surgery. Non-esterified fatty acid (NEFA) in the plasma rapidly increased at the lowest temperature (23°C) reached and other lipids in the plasma decreased during the cooling period. An increase of NEFA and a decrease of triglyceride have been attributed to the action of lipoprotein lipase activity stimulated by heparin. It is also likely that the decrease of other lipids and β-lipoprotein in the plasma results from the transient hypofunction of the liver due to hypothermia. Blood glucose increased during the cooling period, while plasma insulin showed no significant change. Serum DBH reflecting catecholamine also showed no significant change during the cooling or rewarming periods. Therefore, hyperglycemia in hypothermic open-heart surgery may result from the decrease of peripheral utilization of glucose and from the inhibition of insulin secretion due to the transient pancreatic hypofunction.     

Deep hypothermia in cardiovascular surgery

Recent experimental studies and clinical application of deep hypothermia for cardiovascular surgery are reviewed. At most institutions, surface hypothermia alone or in combination with limited cardiopulmonary bypass has been employed. Circulatory dynamics were well maintained following prolonged cardiac arrest at 20°C. Some degree of acidosis usually developed after the arrest period but was gradually corrected during rewarming. Total circulatory occlusion could be maintained for at least one hour at 20°C. without evidence of cerebral damage in infants. Many complex congenital cardiac anomalies, including transposition of the great arteries, total anomalous pulmonary venous return, ventricular septal defect, and tetralogy of Fallot, have been successfully corrected in the first few weeks of life. Less encouraging results have been achieved in patients with infradiaphragmatic total anomalous pulmonary venous return, complete atrioventricular canal, or pulmonary atresia.     

Endocrine reaction pattern in abdominal surgical patients as affected by isoflurane anesthesia

The effects of isoflurane anaesthesia on the per- and postoperative change in blood concentrations of aldosterone, cortisol, dehydroepiandrosterone, insulin, prolactin, thyroxine, t3-uptake, epinephrine, norepinephrine, dopamine, glucose, FFS, lactate, and pyruvate were investigated in connection with major abdominal surgery. Contrary to prolactin levels (8.42 +/- 1.71 ng/ml----46.25 +/- 6.78 ng/ml; p less than 0.001) the plasma concentrations of the adrenal steroids aldosterone, cortisol, and dehydroepiandrosterone sank initially after induction of anaesthesia with thiopentone. However, after skin incision the levels of aldosterone (49.9 +/- 11.6 pg/ml----202.1 +/- 57.6 pg/ml; p less than 0.01), cortisol (16.7 +/- 2.57 ng/dl----25.2 +/- 3.72 ng/dl; p less than 0.01) and DHEA (2.70 +/- 0.99 ng/ml----5.02 +/- 1.03 ng/ml; p less than 0.05) rose significantly. Generally, plasma insulin was not markedly influenced by isoflurane anaesthesia and surgery. No significant alterations in plasma catecholamine concentrations were observed.     

Management of profound accidental hypothermia with cardiorespiratory arrest.

Complete recovery following rapid rewarming is described in three tourists who were admitted in a state of profound hypothermia with total cardiorespiratory arrest (rectal temperature ranging from 19 to 24 C). In all three patients, respiration and circulation had ceased during the rescue operation. Rapid core rewarming was achieved by thoracotomy and continuous irrigation of the pericardial cavity with warm fluids in one patient, whereas in the other two patients rewarming was accomplished with extracorporeal circulation using femoro-femoral bypass. In the first patient, the heart could not be defibrillated earlier than 90 minutes following thoracotomy; in the other patients rewarming was attained very rapidly, and within half an hour after institution of bypass, resuscitation of the heart was successful. The patients fully recovered their intellectual and physical abilities, despite the prolonged periods of circulatory arrest lasting from 2 1/2 to 4 hours. We conclude that rapid core rewarming is the adequate therapy for profound accidental hypothermia with circulatory arrest or low cardiac output. If feasible extracorporeal circulation represents the method of choice because it combines the advantage of immediate central rewarming with the benefit of efficient circulatory support, the heart is rewarmed before the shell, thus preventing the "rewarming shock" due to peripheral vasodilatation. Resuscitative efforts should be promptly initiated and vigorously pursued, even in the state of clinical death; in profound hypothermia neurologic examination is inconclusive regarding prognosis.     

Lidocaine prolongs the safe duration of circulatory arrest during deep hypothermia in dogs

Purpose

To test the hypothesis that lidocaine prolongs the safe period of circulatory arrest during deep hypothermia.

Methods

Sixteen dogs were subjected to cooling, first surface cooling to 30°C and then core cooling to 20°C rectal temperature). The circulation was then stopped for 90 min. In the lidocaine group, 4 mg·kg^?1 lidocaine was injected into the oxygenator two minutes before circulatory arrest and 2 mg·kg^?1 at the beginning of reperfusion and rewarming. The control group received equivalent volumes of normal saline. Post-operatively, using a neurological deficit scoring system (maximum deficit score — 100; minimum — zero indicating that no scored deficit could be detected). Neurological function was evaluated hourly for six hours and then daily for one week. the pharmacokinetic parameters were calculated using one compartment model.

Results

On the seventh day, the neurological deficit score and overall performance were better in the lidocaine (0.83 ± 2.04) than in the control group (8.33 ± 4.08P < 0.05). During the experiment, the base excess values were also better in the lidocaine than in the control group (at 30 min reperfusion: ?4.24 ± 1.30vs ?8.20 ± 2.82P < 0.01, at 60 min reperfusion was ?3.34 ± 1.87vs ?7.52 ± 2.40 (P < 0.01). On the eighth day the extent of pathological changes were milder in the lidocaine group than that in the control group. The elimination half life of lidocaine was 40.44 ± 7.99 during hypothermia and 2.01 ± 4.56 during rewarming.

Conclusions

In dogs lidocaine prolongs the safe duration of circulatory arrest during hypothermia.     

Stress hormone responses to major intra-abdominal surgery during and immediately after sevoflurane-nitrous oxide anaesthesia in elderly patients

We studied the responses of plasma epinephrine, norepinephrine, adrenocorticotropic hormone (ACTH), cortisol, and antidiuretic hormone (ADH) during and immediately after sevoflurane-nitrous oxide anaesthesia supplemented with vecuronium in seven elderly patients (mean 76.6 ± 1.7 SEM) who underwent major intra-abdominal surgery. The plasma concentrations of norepinephrine, ACTH, cortisol, and ADH increased in response to surgical procedures (P <0.05). The plasma concentration of ADH increased to a peak concentration of 189.1 ± 20.7 pg · ml^?1 30 min after skin incision (P < 0.05). the plasma concentrations of epinephrine, norepinephrine, ACTH, and cortisol increased to peak concentrations of 408.6 ± 135.5 pg · ml^?1, 635.7 ± 167.8 pg · ml^?1, 222.6 ± 48.0 pg · ml^?1, and 113.6 ± 67.5 μg · dI^?1, respectively immediately after tracheal extubation (P <0.05). We conclude that, in the elderly patients, the responses of stress hormones to major intraabdominal surgery were preserved during sevoflurane-nitrous oxide anaesthesia sufficient to prevent increases in arterial pressure and heart rate. The strongest responses of epinephrine, norepinephrine, ACTH, and cortisol were elicited immediately after treacheal extubation.     

Prostaglandin E2, prostacyclin, and thromboxane changes during nonpulsatile cardiopulmonary bypass in humans

To study the effect of lung bypass on the production of prostaglandin E2, prostacyclin, and thromboxane A2, we measured simultaneously arterial and venous plasma concentrations of prostaglandin E2, 6-keto-prostaglandin F1 alpha (stable metabolite of prostacyclin), and thromboxane B2 (stable metabolite of thromboxane A2) before, during, and after cardiopulmonary bypass. Seventeen patients (age range 46 to 69 years) undergoing aorta-coronary bypass grafts were investigated. The prostaglandin E2 production rose sharply immediately after the onset of bypass (baseline: 9.7 +/- 2.9 pg/ml to 85 +/- 16.6 pg/ml in venous and 87 +/- 12 pg/ml in arterial plasma, p less than 0.03) and rapidly decreased after pulmonary reperfusion (53 +/- 6.4 and 57 +/- 20 pg/ml, respectively, in venous and arterial plasma at the end of bypass). The increase in prostaglandin E2 was influenced by the heart-lung machine itself (as demonstrated by a closed "bypass" circuit) and by lung bypass. Pulmonary metabolism of prostaglandin E2 was maintained after bypass. The prostacyclin production rose significantly at the beginning of bypass (154 +/- 26 pg/ml venous prebypass level to 361 +/- 94 pg/ml after aortic clamping, p less than 0.03). Prostacyclin decreased progressively during rewarming of the patient, pulmonary reperfusion, and discontinuation of bypass. When prostacyclin decreased, thromboxane B2 production rose significantly and reached peak arterial levels when the lungs were reperfused (112 +/- 33 pg/ml prebypass levels to 402 +/- 101 pg/ml, p less than 0.01). Except for prostaglandin E2, there were no significant differences between arterial and venous plasma levels of these substances. The same prostanoids were also measured in five patients undergoing major orthopedic operations, and no significant changes in prostanoids were observed. Our data demonstrate significant production of prostaglandin E2 in the systemic circulation during cardiopulmonary bypass in humans. They further indicate that lung bypass disturbs the plasma prostaglandin/thromboxane balance.     

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.     

Bispectral index in a 3-year old undergoing deep hypothermia and circulatory arrest

We report a 3-year-old girl who presented with Scimitar syndrome and underwent hypothermic circulatory arrest for correction of anomalous pulmonary veins and an atrial septal defect. In this case the Bispectral Index (BIS) correlated significantly with the gradual onset of hypothermia and circulatory arrest. However, BIS remained low during the rewarming phase of cardiopulmonary bypass, in spite of adequate pump flows and stable haemodynamics. We postulate that this significant lag in BIS during the rewarming phase of deep hypothermic circulatory arrest may represent neuronal bewilderment or perhaps stunning, and differs from previous studies that show significant increase in BIS during rewarming from mild hypothermia.     

Blood flow distribution in infant pigs subjected to surface cooling, deep hypothermia, and circulatory arrest. Deleterious effects in pigs with left-to-right shunts

Surface cooling, deep hypothermia and circulatory arrest have been used effectively for correction of congenital heart defects in infancy. Which patients are best suited for this technique has not been addressed. The addition of surface cooling to deep hypothermia and circulatory arrest provides homogeneous cooling and avoids swelling due to reperfusion injury after circulatory arrest. However, surface cooling in patients with large left-to-right shunts causes increased peripheral resistance and increased shunting which can result in decreased perfusion of vital organs. The purpose of this study is to measure the effect of a large left-to-right shunt on total organ blood flow distribution in infant piglets during surface cooling, deep hypothermia, and circulatory arrest. Eleven 2-week-old piglets had surface cooling, deep hypothermia, and circulatory arrest for 45 minutes, followed by rewarming and weaning from cardiopulmonary bypass. Microspheres (15 mu) were injected before surface cooling, at 28 degrees C, at 15 degrees C, and after weaning from cardiopulmonary bypass. Group I (five piglets) was the control. Group II (six piglets) had a large (6 mm) left-to-right aortopulmonary shunt established before microsphere injection. Cardiac outputs in both Groups I and II decreased with surface cooling. The distribution of cardiac output in Group I did not change with surface cooling; however, Group II pigs showed marked change in distribution of cardiac output, resulting in decreased renal, visceral, and pulmonary flow (p less than 0.05). Amylase determinations before and after surface cooling, deep hypothermia, and circulatory arrest were unchanged in Group I but elevated in Group II (p less than 0.05). These observations suggest altered cellular metabolism in visceral organs during the period of surface cooling which may be compounded by circulatory arrest and rewarming.