Prostacyclin in cardiopulmonary bypass operations.

The effects of prostacyclin (PGI2) on postoperative blood loss and on the deposits which are known to form on filters in the bypass circuit were studied in patients undergoing operations with cardioopulmonary bypass. In this double-blind, randomized study, PGI2 or a placebo solution was administered to 56 patients undergoing elective cardiac operations. At the end of cardipulmonary bypass, the arterial line filter was removed from the circuit and blood losses were accurately recorded. There was no statistically significant difference in either the amount or the pattern of postbypass bleeding between the PGI2 and the control patients. However, the changes in weight of the arterial line filters and their electron microscopic appearances suggest that PGI2 can reduce the deposition of platelets and fibrin on the filter mesh, and in this role it may be of value in reducing visceral injury during cardiac operations.

The benefits of active rewarming after cardiac operations: a randomized prospective trial.

We conducted a prospective, randomized trial of three methods of rewarming patients after hypothermic cardiopulmonary bypass. Patients underwent either coronary artery bypass grafting or first-time valve replacement and were cooled to 32 degrees C during bypass. No significant differences existed among the groups as regards operative or preoperative parameters including hemodynamics and blood use. The patients actively warmed with a convective (Bair Hugger system, 3 hours) or a conductive blanket (electric overblanket, 4 hours) reached normothermia more quickly than those warmed with the space blanket (7 hours). This was reflected in significantly earlier extubation in the former two groups: Bair Hugger system 10.8 +/- 0.6 hours, electric blanket 11.3 +/- 1.0 hours, and space blanket 14.8 +/- 0.8 hours. Patients warmed with the space blanket required a higher dosage of morphine over the first 12 hours than those warmed with the electric blanket (10.4 vs 6.5 mg; p = 0.004), which may account for some of the differences between these two groups. No differences could be demonstrated between the two active blankets. On economic grounds we therefore recommend the reusable electric blanket for routine use.

Serum androgens and gonadotrophins in bronchial carcinoma.

The concentrations of testosterone, free testosterone index derived by two independent techniques (FTI1, FTI2), dehydroepiandrosterone sulphate (DHAS), androstenedione (AND), luteinizing hormone (LH), follicle stimulating hormone (FSH), and sex hormone binding globulin (SHBG) were measured in 38 healthy male controls aged between 40 and 60 years (Group 1) and in 52 male patients with bronchial carcinoma of whom 28 were aged between 40 and 60 years (Group 2) and 24 were aged over 60 years (Group 3). Compared with Group 1, testosterone, FTI1, FTI2, and DHAS were significantly lower (P < 0.001), AND and LH were significantly higher (P < 0.001) and there was no significant difference in FSH or SHBG, in Group 2. No significant difference between Groups 2 and 3 was found for any variable. Analysis of covariance for Groups 2 and 3 combined, showed testosterone, FTI1 and FTI2 were significantly lower in the presence of metastases. These results suggest a more widespread abnormality of androgen metabolism in male patients with bronchial carcinoma than a simple reduction in serum testosterone; DHAS is also significantly reduced while AND is significantly increased. The primary abnormality appears to be at testicular and/or adrenal level as pituitary function appears normal as witnessed by compensatory increases in LH.

Ultrasound detection of cerebral emboli in patients with prosthetic heart valves.

This study was undertaken in 64 patients, 50 with mechanical and 14 with porcine prosthetic valves, to evaluate the incidence of intracranial emboli and their distribution in the basal cerebral arteries. The patients were studied using transcranial Doppler (EME TC2-64B, Uberlingen, Germany), with a monitoring time of two minutes over each of the internal carotid arteries, middle and anterior cerebral arteries, vertebral arteries and the basilar artery. Sixty-three of the 64 patients were stabilized on warfarin at the time of the study. The incidence of emboli signals was significantly higher in patients with mechanical compared to porcine cardiac valves (88% versus 14%, p < 0.01). The number of emboli signals was significantly higher in the anterior compared with the posterior circulation, with a median of eight signals in the internal carotid arteries (95% confidence interval 5-15), 2.5 in the vertebral arteries (95% confidence interval 1-5.5)(p < 0.03). It was also significantly higher in those patients who had undergone double (aortic and mitral) as opposed to those who had undergone single aortic valve replacement: 18 versus two signals per minute (confidence intervals 5-30.5 versus 0.5-3.5) (p < 0.01). It is concluded that subclinical emboli signals are readily detectable using transcranial Doppler and are common in patients with prosthetic heart valves. Their number depends on both the type and the number of the prosthesis, while their distribution in the basal cerebral arteries is consistent with their cardiac source.

Coronary surgery in Europe: comparison of the national subsets of the European system for cardiac operative risk evaluation database.

OBJECTIVE: To compare the national samples of patients who underwent isolated coronary artery bypass grafting (CABG) during the European System for Cardiac Operative Risk Evaluation (EuroSCORE) trial in order to evaluate national differences in epidemiology, patient risk profile and surgical methods. METHODS: From September to November 1995, 11731 patients had CABG in the six largest contributing nations to the EuroSCORE project: Germany, UK, Spain, Finland, France and Italy. The Chi-square and Kruskal-Wallis tests were applied to obtain an international comparison of patient general status, including pre-operative risk factors, cardiac status, critical pre-operative states, rare conditions, urgency of surgery, angina status, coronary lesions, procedures and EuroSCORE risk assessment. RESULTS: Large national samples (from 984 patients in Finland to 3138 in Germany) identified significant differences in epidemiology, risk profile and surgical practice. Regarding epidemiology, CABG accounted for 62.8% of adult cardiac surgery, with a range of 46.2 in Spain to 77.7% in Finland (P<0.001). The mean age was 62.9 years (61.4 in Britain to 64.4 in France, P<0.001). The mean body mass index was 26.8 (26 in France to 27.5 in Finland, P<0.001). With regard to risk profile, diabetes was present in 20.3% of patients (11.8% in Britain to 27.7% in Spain, P<0.001). Chronic renal failure was present in 8.3% (6.8% in Germany to 10.6% in Spain, P<0.001). Chronic airway disease affected 3.8% (1.9% in Italy to 5. 1% in Germany, P<0.001). The mean ejection fraction was 0.56 (0.48 in Britain to 0.58 in Finland, P<0.001). The mean predicted mortality (according to EuroSCORE) was 3.3% (2.8% in Finland to 3.6% in France, P<0.001). The prevalence of chronic congestive heart failure, unstable angina and recent myocardial infarction also showed statistically significant differences. No differences were found for some critical preoperative states (such as immediate preoperative cardiac massage and pre-operative intubation), or for surgery for catheter laboratory complication. Regarding surgical practice, major differences were noted in preoperative intra-aortic balloon use (mean 1%, Finland 0%, Spain 2.3%, P<0.001), the number of mammary artery conduits used (mean 0.9, Spain 0.7, France 1.1, P=0.0001) and the number of distal anastomoses (mean 3, France 2.7, Finland 3.8, P=0.001). CONCLUSION: There are important epidemiological differences in the national cohorts of CABG patients in the EuroSCORE database. Any international comparison of European surgical results must therefore take into account the risk profile of patients by using a compatible risk stratification system.

Transcranial Doppler detection of microemboli in prosthetic heart valve patients: dependency upon valve type.

Transcranial Doppler ultrasound has revealed the existence of cerebrovascular microemboli in asymptomatic patients with prosthetic heart valves. We investigated the relation between the presence and number of emboli signals and valve type. Patients with six types of prosthetic valves (Björk-Shiley monostrut, Medtronic-Hall, Carbomedics, ATS, Carpentier-Edwards standard, Carpentier-Edwards supraannular) were examined using transcranial Doppler ultrasound in two centers. The monitoring time was 30 min over the right middle cerebral artery. All patients were stabilized on warfarin at the time of study. Microemboli signals were identified by their characteristic audiovisual signal and on subsequent spectral analysis, based on accepted criteria. A standard neurologic questionnaire was completed by all patients. The prevalence of microemboli signals varied between 49% (Medtronic Hall) and 97% (Björk-Shiley monostrut), while their number varied between 1 [0-3] (Carpentier-Edwards standard) and 187 [136-240] (Björk-Shiley monostrut) per hour (median and 95% CI). Both parameters were significantly higher in patients with Björk-Shiley monostrut valves compared to the other patient groups. There were no significant differences in the prevalence of neurologic complications among the groups examined (overall 16%), or in emboli numbers between symptomatic and asymptomatic patients. The prevalence and quantity of microemboli signals in patients with prosthetic heart valves, as detected by transcranial Doppler, is dependent upon valve type. The clinical significance of these microemboli signals remains to be further evaluated.

Subclinical embolism in patients undergoing cardiac valve implantation and coronary artery bypass surgery.

Patients undergoing prosthetic valve insertion and coronary artery bypass surgery were examined with transcranial Doppler ultrasound, recently shown to be capable of detecting continuing subclinical emboli in patients with embolic sources. In 30 patients examined at least 1 year after valve surgery, and in whom warfarinisation was stable within defined limits, 20 of 24 patients (83%) with mechanical valves and 3 of 6 patients (50%) with porcine valves had embolic signals. In a serial preoperative and postoperative study in a further 30 patients, of whom 29 had native or bioprosthetic valves, only the one patient with a previous mechanical mitral valve prosthesis had embolic signals preoperatively. The incidence of embolic signals increased to 9 (30%) on the first postoperative day, and 20 (67%) on day 5. In a similar serial study in 25 patients undergoing coronary bypass surgery, 8 (32%) had preoperative embolic signals, which were explicable by cardiac and/or carotid disease in 6 cases. The embolus signal incidence and count did not increase postoperatively in this group. No embolic signals were found in 15 volunteer controls. The results indicate that prosthetic valves cause continuing microembolisation, detectable by transcranial Doppler; coronary artery bypass cases may have incidental embolic signals which are unaffected by cardiac surgery. This new application of Doppler ultrasound may improve the clinical assessment of embolic risk of new prosthetic valve types and deserves further examination.

Risk factors and outcome in European cardiac surgery: analysis of the EuroSCORE multinational database of 19030 patients.

OBJECTIVE: To assess risk factors for mortality in cardiac surgical adult patients as part of a study to develop a European System for Cardiac Operative Risk Evaluation (EuroSCORE). METHODS: From September to November 1995, information on risk factors and mortality was collected for 19030 consecutive adult patients undergoing cardiac surgery under cardiopulmonary bypass in 128 surgical centres in eight European states. Data were collected for 68 preoperative and 29 operative risk factors proven or believed to influence hospital mortality. The relationship between risk factors and outcome was assessed by univariate and logistic regression analysis. RESULTS: Mean age (+/- standard deviation) was 62.5+/-10.7 (range 17-94 years) and 28% were female. Mean body mass index was 26.3+/-3.9. The incidence of common risk factors was as follows: hypertension 43.6%, diabetes 16.7%, extracardiac arteriopathy 2.9%, chronic renal failure 3.5%, chronic pulmonary disease 3.9%, previous cardiac surgery 7.3% and impaired left ventricular function 31.4%. Isolated coronary surgery accounted for 63.6% of all procedures, and 29.8% of patients had valve operations. Overall hospital mortality was 4.8%. Coronary surgery mortality was 3.4% In the absence of any identifiable risk factors, mortality was 0.4% for coronary surgery, 1% for mitral valve surgery, 1.1% for aortic valve surgery and 0% for atrial septal defect repair. The following risk factors were associated with increased mortality: age (P = 0.001), female gender (P = 0.001), serum creatinine (P = 0.001), extracardiac arteriopathy (P = 0.001), chronic airway disease (P = 0.006), severe neurological dysfunction (P = 0.001), previous cardiac surgery (P = 0.001), recent myocardial infarction (P = 0.001), left ventricular ejection fraction (P = 0.001), chronic congestive cardiac failure (P = 0.001), pulmonary hypertension (P = 0.001), active endocarditis (P = 0.001), unstable angina (P = 0.001), procedure urgency (P = 0.001), critical preoperative condition (P = 0.001) ventricular septal rupture (P = 0.002), noncoronary surgery (P = 0.001), thoracic aortic surgery (P = 0.001). CONCLUSION: A number of risk factors contribute to cardiac surgical mortality in Europe. This information can be used to develop a risk stratification system for the prediction of hospital mortality and the assessment of quality of care.

Wound colonisation following cardiac surgery. Reduction by adjuvant use of preincisional, presternal antibiotic infiltration: a double blind prospective randomised study.

In a double blind, prospective, randomised study of 100 patients undergoing elective cardiac surgery, a significant (p less than 0.01) reduction in wound colonisation, defined as positive culture of any wound discharge irrespective of wound appearance, occurred in those receiving preincisional presternal antibiotic infiltration (2%) as compared to a control group who received a similar volume of normal saline by the same route (24%). Both groups received, in addition, the same conventional intravenous regimen of broad spectrum antibiotic. A comparable concurrent group of patients, not entered into the study, demonstrated a wound colonisation rate similar to the trial control group (22%), thus excluding an adverse bias from the control saline infiltration. Analysis of control cases demonstrated a significant (p less than 0.001) discriminant effect in the degree of preoperative haemodilution with haematocrit falling on bypass by a mean of 25% in those who developed wound colonisation as compared to 13% in those who did not.

Detection of microemboli by transcranial Doppler ultrasound.

Doppler ultrasound detection of abnormally high-pitched signals within the arterial waveform offers a new method for diagnosis, and potentially for prediction, of embolic complications in at-risk patients. The nature of Doppler "microembolic" signals is of particular interest in patients with prosthetic heart valves, where a high prevalence of these signals is observed. Monitoring the middle cerebral artery with 2-MHz transcranial Doppler ultrasound (TC-2000, Nicolet Biomedical; Warwick, UK), we looked for microemboli signals in 150 patients (95 women and 55 men), and found 1 or more signals during a 30-min recording in 89% of 70 patients with Bjork-Shiley valves (principally monostrut), 54% of 50 patients with Medtronic-Hall valves, and 50% of 30 patients with Carpentier-Edwards valves (p < 0.001, chi 2). In the patients with Bjork-Shiley valves, the mean number of signals per hour was 59 (range, 42-86; 95% confidence interval), which was significantly higher than the mean in patients with Medtronic-Hall and Carpentier-Edwards valves (1.5[range, 0.5-2.5] and 1 [range, 0-5.3], respectively; both p < 0.04, multiple comparisons. Bonferroni correction). In the patients undergoing serial pre- and postoperative studies, the causative role of the valve implant was emphasized. There was no correlation between the number of emboli signals and a prior history of neurologic deficit, cardiac rhythm, previous cardiac surgery, or the intensity of oral anticoagulation, in patients with prosthetic heart valves. In Bjork-Shiley patients, dual (mitral and aortic) valves were associated with more signals than were single valves. In Medtronic-Hall patients, the signal count was greater for valves in the aortic position than it was for valves in the mitral position. Comparative studies of Doppler emboli signals in other clinical settings suggest a difference in composition or size of the underlying maternal between prosthetic valve patients and patients with carotid stenosis. These studies also suggest that the signals are of gaseous origin in valve patients. The clinical significance of continuing microembolism remains to be determined.

Surgical management of native valve endocarditis.

From 1972 to 1981 40 patients have required urgent valve replacement for left-sided bacterial endocarditis. The aortic valve was replaced in 31 patients, the mitral valve in four, and both in five patients. Twenty-six patients (65.5%) were in functional class IV heart failure according to the New York Heart Association criteria, and 13 patients (32.5%) were in class III heart failure at the time of operation. One patient in class II was operated on urgently for multiple cerebral embolism but died of fatal cerebral haemorrhage. In 22 patients (55%) there were no pre-existing valvular lesions and these patients were found to be more liable to develop severe haemodynamic failure. Premature closure of the mitral valve, documented by M-mode echocardiography, was a useful diagnostic aid and successfully determined the best timing of surgery in 14 out of 20 patients with severe aortic regurgitation. Cardiac arrest before operation appeared to be a significant risk factor (p = 0.0015) unless followed by immediate cardiopulmonary bypass. There were eight operative deaths (20%). Of 26 patients who were in functional class IV heart failure, 19 were operated on within four days of their haemodynamic deterioration and all survived. The operation was delayed in the remaining seven patients and none of them survived (p = 0.000003). There were no operative deaths among the patients in class III heart failure. There was only one episode of reinfection in the 16 patients followed up for at least three years. The duration of postoperative antibiotic treatment (four to six weeks in our patients), rather than any preoperative antibiotic regimen, seems to be important for preventing reinfection. At present there are 28 survivors, of whom 24 are in functional class I and four in class II.

A simplified procedure for preparing innervated gastric pouches.

Conventional innervated gastric pouches can be technically difficult to construct, and fistula formation between the pouch and the main stomach cavity is a common problem. This paper describes the method of construction of a small pouch on the lesser curvature (LC pouch) which we have found to be relatively free of these difficulties. Compared with the Pavlov-type pouch, this pouch gives a stronger acid secretory response to a meat meal. Furthermore, the acid secretory response was prompt to insulin hypoglycemia and sham feeding.

A double blind study of prostacyclin in cardiopulmonary bypass surgery.

In a double-blind placebo-controlled trial of 48 patients requiring open heart surgery, prostacyclin (PGI2) was infused in a dose of 20 ng/kg/min throughout cardiopulmonary bypass. When compared with the placebo group, the patients given active PGI2 were found to have significantly higher platelet counts from 30 min after commencement of bypass and in the immediate post-operative period, and to have significantly less elevation of the platelet secretory proteins, beta thromboglobulin and platelet factor 4 during bypass. The mean weight increase in the arterial line filters was significantly greater in the placebo-treated patients than in the PGI2 group. It is suggested that infused PGI2 decreases platelet activation during cardiopulmonary bypass and that further studies are required to establish its clinical value in this situation.

Low serum testosterone as an indicator of metastatic bronchial carcinoma.

Serum testosterone concentrations were measured preoperatively in 39 men undergoing thoracotomy for histologically proved bronchial carcinoma, in 10 patients with pulmonary opacities that transpired to be non-malignant (benign group) and in 23 men were undergoing minor elective surgical procedures (control group). Thirteen of the 39 patients with known bronchial carcinoma were considered to have had curative surgery and 26 a palliative procedure when operative and pathological findings were taken into consideration. Low serum testosterone concentrations (less than 12 nmol/l) were detected in four patients in the curative group, in 22 in the palliative group (chi 2 test: p less than 0.001), three in the benign group, and in two patients in the control group. A low serum testosterone concentration in patients with bronchial carcinoma may be an indicator of metastatic disease and sequential serum testosterone estimations may prove useful in the follow up of patients thought to have undergone curative surgery.

Prevalence and characteristics of intracranial microemboli signals in patients with different types of prosthetic cardiac valves.

BACKGROUND AND PURPOSE: Transcranial Doppler detection of microemboli is widely described, but there is no clear evidence of the clinical significance or nature of the embolic material in vivo. Thromboembolism is a major cause of morbidity in patients with prosthetic cardiac valves. We undertook this study to evaluate the prevalence and the acoustic characteristics of microembolic signals in three groups of patients with different prosthetic valves. METHODS: One hundred seventy-nine patients with prosthetic cardiac valves (85 Björk-Shiley, 56 Medtronic-Hall, and 38 Carpentier-Edwards) and 25 normal subjects were examined using transcranial Doppler. Monitoring time was 30 minutes over the right middle cerebral artery. RESULTS: The prevalence and numbers of embolic signals were significantly higher in patients with Björk-Shiley compared with those with Medtronic-Hall and Carpentier-Edwards valves (89% versus 50% and 53%, respectively; P < .001, chi 2; 156 [112, 204] versus 2 [1, 4] and 2 [1, 4] signals/h, respectively; median [95% nonparametric confidence interval], both P < .001, multiple comparisons, Bonferroni correction). The signal intensity was significantly higher in patients with Björk-Shiley and Medtronic-Hall valves than patients with Carpentier-Edwards valves (2435 [2345, 2527] and 2120 [1745, 2483] versus 225 [184, 287] power units, median [95% confidence interval], both P < .001). No correlation was found between embolic signal numbers and clinical parameters including history of neurological deficit, cardiac rhythm, duration of artificial valve, previous cardiac operations, or intensity of anticoagulation. Embolic signals were not detected in any of the control subjects. CONCLUSIONS: Our data showed that the prevalence, quantity, and acoustic characteristics of Doppler embolic signals differ in patients having three different types of prosthetic heart valves. However, no correlation with clinical parameters was identified.

Achalasia-like syndrome in systemic sclerosis.

Two methods of quantifying oesophageal emptying for liquids have been used to assess the dysphagia of patients with systemic sclerosis: the oesophageal infusion scintiscan and the timed Gastrografin swallow. Upper gastrointestinal endoscopy and oesophageal manometry were also performed. Thirteen patients with oesophageal symptoms were studied. Eight had dysphagia, and all of these had endoscopies with no evidence of oesophagitis or stricture. Four of these eight subjects had gross delay of oesophageal emptying for fluids, and manometry showed absence of oesophageal peristalsis and incomplete relaxation of the lower oesophageal sphincter. This abnormality is similar to achalasia. Two of these four patients have benefited from pneumatic dilatation with improvement in their severe dysphagia. We believe that pneumatic dilatation should be considered in patients with systemic sclerosis and severe dysphagia where reflux oesophagitis is not apparent.

Effect of sodium oleate on plasma secretin concentration and pancreatic secretion in dog.

The effects of sodium oleate and triglyceride infused into the duodenum of dogs with chronic pancreatic fistulas on pancreatic secretion and plasma immunoreactive secretin were investigated. The responses were compared with those following intravenous secretin infusions. Oleate markedly increased pancreatic water and bicarbonate secretion in a dose-related fashion, and these increases were accompanied by a small, but significant rise in the level of circulating immunoreactive secretin. No change in pancreatic secretion or in plasma secretin level was observed by the administration of triglyceride. Comparison of the bicarbonate response after oleate infusion with that after secretin administration suggests that the pancreatic stimulatory effect of intraduodenal sodium oleate is mediated to a major extent by the release of endogenous secretin.

Drug sensitivity of non small cell carcinoma of lung by clonogenic assay in several media.

Lung tumours of non small cell pathology were cultured by clonogenic assay in several media. Culture was successful in spleen conditioned medium, but only 57% grew and low plating efficiencies (PE) meant that only 23% of the original number produced significant drug results. Comparison of rat erythrocyte lysate (REL) medium with serum free defined medium (HITES) and HITES + 10% FBS demonstrated clear enhancement of PE in REL although growth was 100% successful in all these media. Ninety-three percent of samples tested against drugs in REL produced significant results. A later comparison of REL with McCoy's 5A + rbc +/- hydrocortisone produced relatively poor culture success for these 3 media and equivocal growth patterns. Low PE was attributed to age of rats used for rbc. Vindesine and cis-platinum cytotoxicity in spleen conditioned medium were 61% and 15% sensitivity respectively. These do not concur with clinical experience but the figures for overt resistance, at 39% and 69%, correspond with expected non-responders to these regimes. Drug testing in REL produced figures correlating more closely with clinical performance at 45% sensitivity to platinum and 36% of patients sensitive to both drugs, but the vindesine sensitivity at 55% is again discrepant with performance of this drug as a single agent.

Wound prophylaxis in thoracic surgery: a new approach.

A prospective double blind, randomised study was performed in 100 patients undergoing major elective thoracic surgery to assess a new method of prophylaxis of wound infection using one preincisional intraparietal infiltration of cefuroxime sodium along the line of proposed incision as the sole protection against wound infection. A significant (p less than 0.01) reduction in the incidence of wound infection occurred in the antibiotic treated group (2%) compared with the control group (20%), who received by the same route the same volume of saline only. The groups were comparable with respect to age, sex, pathological condition, and operative variables. The use of additional antibiotics was significantly greater in the control group (p less than 0.01), largely owing to a much greater incidence of postoperative pulmonary infection in the control group (60%) than in the antibiotic treated group (40%). No morbidity was associated with this technique. The organisms found in oesophageal and bronchial operative luminal specimens did not correlate with postoperative wound or pulmonary infection or with organisms causing these infections. Reductions in wound and pulmonary infection rates equivalent to those produced by conventional multiple dose parenteral regimens were achieved by this technique.

Mediastinal imaging in lung cancer.

Sixty-six patients with lung cancer underwent mediastinal staging with gallium scanning, CT scanning and mediastinal exploration at mediastinoscopy and/or thoracotomy. Histological findings at time of mediastinal exploration were correlated with the results of the non-invasive staging scans. Gallium scanning had an accuracy of 78.8 per cent and CT scanning had an accuracy of 77.3 per cent. There was no evidence of increased test accuracy by performing both scans in the same individual. Either scanning technique may be utilised as a simple non-invasive mediastinal staging procedure, and where negative it is appropriate to proceed directly to thoracotomy.