Perioperative monitoring of platelet function in paediatric cardiac surgery by thromboelastometry, or platelet aggregometry?

BACKGROUND: Impaired platelet function increases the risk of bleeding complications in cardiac surgery. Reliable assessment of platelet function can improve treatment. We investigated whether thromboelastometry detects clinically significant preoperative, perioperative, and postoperative adenosine diphosphate (ADP)-dependent platelet dysfunction in paediatric cardiac surgery patients. METHODS: Fifty-seven children were included in a single-centre prospective observational study. Clot formation (modified rotational thromboelastometry with heparinase, HEPTEM) and platelet aggregation (multiple electrode aggregometry) were analysed at five time points before, during, and after surgery. The accuracy of thromboelastometric indices of platelet function [maximal clot firmness (MCF) and clot formation time (CFT)] to detect ADP-dependent platelet dysfunction (defined as ADP-induced aggregation ≤30 units) was calculated with receiver operating characteristics analysis, which also identified optimal cut-off levels. Positive and negative predictive values for the identified cut-off levels (CFT≥166 s; MCF≤43 mm) to detect platelet function were determined. RESULTS: The MCF and CFT were highly accurate in predicting platelet dysfunction during cardiopulmonary bypass [CPB; area under the aggregation curve 0.89 (95% confidence interval 0.80-0.97) and 0.86 (0.77-0.96), respectively] but not immediately after CPB [0.64 (0.48-0.79) and 0.67 (0.52-0.82), respectively] or on arrival at the intensive care unit [0.53 (0.37-0.69) and 0.60 (0.44-0.77), respectively]. The positive and negative predictive values were acceptable during CPB (87 and 67%, respectively, for MCF≤43 mm; 80 and 100% for CFT≥166 s) but markedly lower after surgery. CONCLUSION: In paediatric cardiac surgery, thromboelastometry has acceptable ability to detect ADP-dependent platelet dysfunction during, but not after, CPB.

Thoracolumbar epidural blockade as adjunct to high dose fentanyl/midazolam anesthesia in coronary surgery: effects of sternotomy.

The present study tests the hypothesis that the changes in myocardial lactate metabolism in the early period of coronary surgery are caused by raised adrenergic activity, and that these are preventable by the addition of thoracolumbar epidural blockade to high dose fentanyl/midazolam anesthesia. Twenty-seven male beta 1-blocked patients undergoing coronary surgery were included in a prospective, controlled, randomized study. High dose fentanyl/midazolam anesthesia alone (control) or supplemented with thoracolumbar epidural blockade (treatment) was used. Measurements were performed before the induction of anesthesia and after sternotomy. After sternotomy adrenaline (A) and noradrenaline (NA) had decreased and were both in the low range, especially in the epidural group (P < 0.01). Arterial pressures decreased in both groups, especially in the epidural group, where coronary perfusion pressure (CPP) decreased from 61 (42-88) to 48 (33-64) mm Hg; Systemic vascular resistance (SVR) decreased with 30% in the epidural group (P < 0.01), but not significantly in the control group. The myocardial fractional extraction of lactate decreased in both groups, from 33 (10-45) to 13 (0-42)% in the control group (P < 0.01), and from 36 (19-43) to 10 (2-20)% in the epidural group. It is concluded that high dose fentanyl/midazolam anesthesia prevents hyperadrenergic activity in the early phase of coronary surgery, but cannot eliminate changes in myocardial lactate metabolism. The addition of the thoracolumbar epidural blockade to high dose fentanyl/midazolam anesthesia offers no obvious benefits in the early phase of coronary surgery.

Trends in incidence, clinical findings and outcome of acute and elective cholecystectomy, 1970-1986.

OBJECTIVE: To assess time trends in the incidence, clinical findings, and outcome of conventional acute and elective cholecystectomy. DESIGN: Single-institution time series analysis. SETTING: University hospital, Sweden. SUBJECTS: A consecutive series of 2926 patients operated on for acute or chronic gallbladder disease in a defined Swedish population. MAIN OUTCOME MEASURES: Changes in the incidence and outcome of acute and elective cholecystectomy. RESULTS: From period I (1970-1978) to period II (1979-1986), the mean rate of acute operations increased from 10 to 30/100,000 inhabitants/year and that of elective operations decreased from 190 to 120/100,000 inhabitants/year. There was therefore a negative correlation between the rate of elective and acute operations (r = -0.58, p < 0.02). This was strongest when the rate of elective operations in any one year was correlated with the rate of acute operations two years later (r = -0.71, p < 0.01). In both groups the proportion of patients over 70 years old increased significantly. The female:male ratio decreased significantly for acute but not elective operations (mean 2.6 in period I and 1.0 in period II). The length of history and the number of previous admissions to hospital with gallstone disease decreased significantly for both groups, as did prevalence of common bile duct stones detected at cholecystectomy. Morbidity did not seem to change, though a general improvement may have been concealed, because patients were older in period II and postoperative mortality was lower than in period I. Complications were least common among patients with a short or no previous history of symptoms attributable to gallstones. CONCLUSIONS: The rate of elective cholecystectomy seems to have some influence on the future rate of acute cholecystectomy. When symptoms of gallstone disease develop, treatment should not be delayed unnecessarily.

Renal function during cardiopulmonary bypass: influence of pump flow and systemic blood pressure.

The influence of systemic blood flow (pump flow) and arterial blood pressure on renal function was studied during hypothermic cardiopulmonary bypass (CPB) in 14 male patients where the pump flow rate was varied between 1.45 and 2.20 l.min-1 m-2. Renal blood flow (RBF) was measured in the left renal vein with retrograde thermodilution technique and urinary flow and circulatory variables were measured with an on-line computer set-up. During CPB the RBF comprised 12-13% of the systemic blood flow and was positively related to systemic blood pressure (r = 0.71; P < 0.001) and pump flow rate (r = 0.69; P < 0.001). These findings indicate that the renal autoregulation was not operative during the hypothermic CPB period. According to multiple regression analysis, RBF was primarily determined by the pump flow rate and systemic blood pressure was of secondary importance. Urinary flow increased during hypothermic CPB and became closely related to blood pressure and pump flow. According to multiple regression analysis, urinary flow was primarily determined by systemic blood pressure.

Calculation of renal extraction during high diuresis and low renal plasma flow conditions.

The renal fractional extraction (Ex) is a parameter describing the ability of the kidneys to remove a substance x from the circulating plasma. Ex is calculated often as the ratio between the arteriovenous concentration difference and the arterial concentration. This method simplifies the calculations but it is associated with an underestimation of Ex. In the study described here, a theoretical analysis of the error is made, with a graphical presentation of its magnitude in different diuresis/renal plasma flow (RPF) ratios and at different levels of Ex. The error was analysed also in a clinical situation where the renal extraction of PAH (EPAH) and EDTA (EEDTA) were determined in six patients during different stages of cardiac surgery. The underestimation of EPAH was seldom more than 4%, while EEDTA was underestimated often with more than 20%. It is concluded that the simplified formula is accurate when calculating the renal extraction for substances like PAH, with a normally high extraction, even if the diuresis/RPF ratio is high. For substances with low extractions, e.g. filtration markers, in some clinical and experimental situations it is necessary to take the renal plasma flows into consideration or to arrange for low urine production to avoid significant errors.

Absent diastolic cerebral blood flow velocity after circulatory arrest but not after low flow in infants.

It is controversial whether profound hypothermia (15 degrees C) provides adequate cerebral protection during a limited period of total circulatory arrest during pediatric cardiac surgery. In the present study, transcranial Doppler echography was used to monitor the blood flow velocity (BFV) pattern in the middle cerebral artery (MCA). The purpose of the study was to investigate the influence of a period of circulatory arrest on MCA BFV, as judged from the reperfusion flow velocity pattern. The MCA BFV was studied in 22 small children undergoing profound hypothermic cardiac operations after induction of anesthesia. Twelve of the children had a period of profound hypothermic circulatory arrest (15 to 74 minutes; arrest group). Circulation was maintained in the remaining 10 children (nonarrest group). Time-averaged MCA BFV was decreased and diastolic BFV was absent immediately after cardiopulmonary bypass in 10 of 12 children in the arrest group. In contrast, only 1 of 10 patients in the nonarrest group (p < 0.05) showed this pattern. Diastolic BFV normalized 54 to 328 minutes after the arrest in the arrest group. Circulatory arrest during profound hypothermia is followed by a period of low cerebral perfusion, whereby time-averaged MCA BFV is decreased and MCA BFV is absent during diastole. We speculate that this can be explained by an increase in intracranial pressure after brain edema.

Acute renal failure after coronary surgery--a study of incidence and risk factors in 2009 consecutive patients.

To obtain a model for the prediction of acute renal failure (ARF) after coronary surgery, 2009 consecutive patients were investigated. ARF was defined as a peak postoperative serum creatinine value exceeding the preoperative value by 50% or more or a need for dialysis. A postoperative increase in serum creatinine of less than 50% was associated with an early mortality (< or = 30 days postop.) of 0.4%. Sixteen per cent of the patients increased their serum creatinine by more than 50% and in this group there was a mortality of 1.3%. Twenty-five patients (1.2%) required postoperative haemodialysis because of ARF and of these 11 (44%) died early, whereas another 7 patients with chronic renal failure, requiring both pre- and postoperative haemodialysis, all survived. Peak postoperative serum creatinine and changes from the preoperative value were analyzed and related to clinical variables. Multivariate analysis indicated that high preoperative serum creatinine, high age and postoperative haemodynamic instability were the most important risk factors for developing renal failure. A logistic model including these risk factors versus the probability of developing ARF is presented.

High-dose intravenous beta 1-blockade in patients early after cardiac operations. Negative inotropism versus myocardial oxygen economy.

A high adrenergic strain during reperfusion after ischemia impedes functional recovery. Conversely, adrenergic blockade may be beneficial during reperfusion. Negative inotropic effects may outweigh the expected benefit, however. Against this background hemodynamic and metabolic effects of early postoperative infusion with the beta 1-selective agent metoprolol were studied in 22 patients after coronary operations. During basal postoperative conditions, intravenous metoprolol reduced cardiac index and stroke volume index compared with control patients, while other variables were unaffected. During the higher adrenergic level of a dopamine infusion (7 micrograms/kg per minute), the heart rate, rate pressure product, and myocardial oxygen uptake were attenuated in proportion to the plasma level of metoprolol. Intravenous beta 1-blockade did not affect the cardiac output or stroke volume responses to dopamine (the cardiac output was still, however, 19% lower than in control patients). A release of myocardial creatinine kinase isoenzyme myocardial band was observed during dopamine infusion, suggesting that myocardial ischemia was induced. The release was not influenced by metoprolol, but it correlated with heart rate (r = 0.60; p < 0.01). It is concluded that infusion of metoprolol early after coronary operations depresses myocardial contractility with some 19%, which was without clinical significance in straightforward patients; the increased myocardial metabolic demand during a period of increased adrenergic stress was attenuated by metoprolol. This may be of importance for myocardial recovery.

Effects of insulin on myocardial uptake of branched chain amino acids soon after cardiac operations.

Infusion of insulin-glucose-potassium is used to support the failing heart after cardiac operations. Although the effects on myocardial uptake of carbohydrates and lipids have been described, the effects on myocardial extraction of amino acids are unknown. This study was undertaken to clarify the effect of insulin-glucose-potassium on the pattern of amino acid uptake/release in myocardial and skeletal muscle after coronary operations. The amino acid uptake/release of the heart and of the leg was studied in 18 patients 1 hour after coronary bypass operations. The patients were randomized to treatment with 25 U of fast-acting insulin as a bolus injection followed by a continuous infusion of 1 U/kg body weight for 1 hour, or to serve as control patients. The hyperinsulinemic "clamp" technique was used to keep blood glucose unchanged during the study. In the insulin-treated group, the arterial concentration of 17 of 22 individual amino acids, including the three branched chain amino acids, decreased, the remainder being unchanged. The amino acid uptake/release of the leg was unchanged. The net myocardial uptake of leucine and isoleucine shifted to a no-uptake/no-release in the insulin-treated group, whereas the no-uptake/no-release of tyrosine and phenylalanine turned into a significant release. A positive correlation was observed between arterial concentration and myocardial uptake/release of the three branched chain amino acids. It is suggested that insulin, by lowering the arterial concentration of leucine and isoleucine, inhibited the myocardial uptake of these amino acids. This may have a negative effect on postoperative myocardial protein balance suggested by the release of tyrosine and phenylalanine.

Dopamine and high-dose insulin infusion (glucose-insulin-potassium) after a cardiac operation: effects on myocardial metabolism.

Myocardial insulin resistance, in association with surgical stress, restricts the availability of carbohydrates and increases the load of free fatty acids (FFAs) on the heart. On theoretical grounds adrenergic drugs may be expected to aggravate this situation, whereas the opposite is expected from insulin. The influence of dopamine and a combination of dopamine (7 micrograms/kg body weight/min) and high-dose insulin (7 IU/kg) on myocardial energy metabolism was studied in 19 patients 4 to 6 hours after a coronary operation. Infusion of dopamine (7 micrograms/kg body weight/min) induced metabolic changes that may be unfavorable to the strained myocardium. There was an increase of the myocardial FFA load and a rise in myocardial oxygen expenditure by 60% to 70%. There changes were, however, not matched by an increase in myocardial substrate uptake. "Oxygen wastage" of FFA metabolism at high circulating catecholamine levels is suggested. There were also signs suggesting an amplified systemic trauma response: systemic oxygen consumption increased by 15%, and an increase in the arterial levels of FFAs, glucose, and ketones was observed. Divergent metabolic effects of dopamine and insulin were demonstrated. The most prominent metabolic effects of adding high-dose insulin to dopamine were a marked reduction of arterial FFA levels and a shift toward myocardial carbohydrate utilization at the expense of FFAs. Myocardial uptake of FFAs ceased. Myocardial insulin resistance may thus to a significant extent be overcome by supraphysiological doses of insulin, even during infusion of adrenergic drugs.

Drainage by endoscopic endoprosthesis in biliary obstruction. A report of initial experience.

Biliary drainage by endoscopic, transpapillary insertion of endoprosthesis was attempted in 38 patients with obstructive jaundice and was successful in 25. The procedure was palliative in 17 cases and preoperative in eight. Benefit was obtained by ten of the former and seven of the latter patients, while in eight the serum bilirubin did not fall despite adequate catheterization. In two intubated patients with recurrent nonterminal jaundice, the endoprostheses were repeatedly changed; the median time to clogging was 51 (8-77) days. Cholangitis developed in 15 of the total 38 patients. Antibiotic prophylaxis, though not routinely used, is recommended for all cases with biliary stasis. Unimpeded bile flow was not ensured with 7 F endoprostheses, whose patency time tended to be short. By using sizes 10-12 F the authors hope to improve bile flow, thereby diminishing obstruction, stagnation and infection and prolonging patency. In selected cases the method may offer an alternative to the percutaneous approach, and possibly also to surgical bypass.