Clinical research in anaesthesia; randomized controlled trials or observational studies?
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Biomedical subjects
Publications and source records attributed to R O Feneck.
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OBJECTIVES: We sought to evaluate the efficacy of recombinant human antithrombin III for restoration of heparin responsiveness in heparin-resistant patients scheduled for cardiac surgery. METHODS: This was a multicenter, randomized, double-blind, placebo-controlled study in heparin-resistant patients undergoing elective cardiac surgery. Patients were considered heparin resistant if the activated clotting time was less than 480 seconds after 400 U/kg heparin. Fifty-two heparin-resistant patients were randomized into 2 cohorts. One cohort received a single bolus (75 U/kg) of recombinant human antithrombin III (n = 28), and the other, the placebo group (n = 24), received a normal saline bolus. If the activated clotting time remained less than 480 seconds, this was defined as treatment failure, and 2 units of fresh frozen plasma were transfused. Patients were monitored for adverse events during hospitalization. RESULTS: Six (21%) of the patients in the recombinant human antithrombin III group received fresh frozen plasma transfusions compared with 22 (92%) of the placebo-treated patients ( P < .001). Two units of fresh frozen plasma did not restore heparin responsiveness. There was no increased incidence of adverse events associated with recombinant human antithrombin III administration. Postoperative 24-hour chest tube bleeding was not different in the 2 groups. Surrogate measures of hemostatic activation suggested that there was less activation of the hemostatic system during cardiopulmonary bypass in the recombinant human antithrombin III group. CONCLUSION: Treatment with recombinant human antithrombin III in a dose of 75 U/kg is effective in restoring heparin responsiveness and promoting therapeutic anticoagulation for cardiopulmonary bypass in the majority of heparin-resistant patients. Two units of fresh frozen plasma were insufficient to restore heparin responsiveness. There was no apparent increase in bleeding associated with recombinant human antithrombin III.
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BACKGROUND AND OBJECTIVE: The study was designed to identify those factors associated with early tracheal extubation following cardiac surgery. Previous studies have tended to concentrate on surgery for coronary artery bypass or on other selected cohorts. METHODS: Sequential cohort analysis of 296 unselected adult cardiac surgery patients was performed over 3 months. RESULTS: In total, 39% of all patients were extubated within 6 h, 89% within 24 h and 95% within 48 h. Delayed extubation (>6 h after surgery) appeared unrelated to age, gender, body mass index, a previous pattern of angina or myocardial infarction, diabetes, preoperative atrial fibrillation, and preoperative cardiovascular assessment, as well as other factors. Delayed tracheal extubation was associated with poor left ventricular, renal and pulmonary function, a high Euroscore, as well as the type, duration and urgency of surgery. Early extubation (<6 h) was not associated with a reduced length of stay in either the intensive care unit or in hospital compared with patients who were extubated between 6 and 24 h. In these groups, it is presumed that organizational and not clinical factors appear to be responsible for a delay in discharge from intensive care. Patients who were extubated after 24 h had a longer duration of hospital stay and a greater incidence of postoperative complications. Postoperative complications were not adversely affected by early tracheal extubation. CONCLUSIONS: In an unselected sequential cohort, both patient- and surgery-specific factors may be influential in determining the duration of postoperative ventilation of the lungs following cardiac surgery. In view of the changing nature of the surgical population, regular re-evaluation is useful in reassessing performance.
BACKGROUND AND OBJECTIVE: We set out to compare the efficacy of clevidipine and sodium nitroprusside infusions in the control of blood pressure and the haemodynamic changes they produce in hypertensive patients after operation for elective coronary bypass grafting. METHODS: Thirty patients were randomly allocated to receive either clevidipine or sodium nitroprusside after their mean arterial pressure (MAP) had reached > 90 mmHg for at least 10 min in the postoperative period. The MAP was continuously measured and related to time. Thus, the efficacy of the drugs in controlling arterial pressure could be inversely related to the total area under the MAP-time curve outside a target MAP range of 70-80 mmHg normalized per hour (AUC(MAP) mmHg min h(-1)). Haemodynamic variables and the number of dose-rate adjustments required to maintain MAP were also studied. RESULTS: There was no statistically significant difference in the efficacy (AUC(MAP) mmHg min h(-1)) of clevidipine (106 +/- 25 mmHg min h(-1)) compared with sodium nitroprusside (101 +/- 28 mmHg min h(-1)). Nor was any significant difference found in the total number of dose adjustments required to control MAP within the target range. The heart rate in patients receiving clevidipine increased less than in those given sodium nitroprusside. Stroke volume, central venous pressure and pulmonary artery pressure were significantly reduced upon administration of sodium nitroprusside but not of clevidipine. CONCLUSIONS: There was no significant difference between clevidipine and sodium nitroprusside in their efficacy in controlling MAP. The haemodynamic changes, including tachycardia, were less pronounced with clevidipine than with sodium nitroprusside.
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OBJECTIVE: To compare the hemodynamic effects, efficacy, and safety of intravenous milrinone (M), 50 microg/kg during 10 minutes followed by 0.5 microg/kg/min, with intravenous dobutamine (D), 10 to 20 microg/kg/min, in patients with low cardiac output after cardiac surgery. DESIGN: Randomized, open-label, multicenter study. SETTING: Cardiothoracic surgery departments, operating rooms, and intensive care units in 6 university hospitals. PARTICIPANTS: Patients (n = 120; 60 per group) after elective cardiac surgery. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Analysis compared the hemodynamics at baseline and the percentage change from baseline during 4 hours of the drug infusion. The incidence of adverse events was recorded. Both groups had low mean (+/- SEM) cardiac indices (M, 1.6 ([0.03] L/min/m(2); D, 1.7 [0.03] L/min/m(2)) in association with adequate mean pulmonary capillary wedge pressures (M, 13.7 [1.3] mmHg; D, 12.7 [1.9] mmHg) at baseline. Group M had significantly higher systemic arterial pressures and systemic vascular resistances compared with group D; otherwise, the hemodynamics in both groups were comparable. During the study, hemodynamic responses included the following: group D had greater increases in cardiac index (at 1 hour, D = 55%, M = 36%; p < 0.01), heart rate (at 1 hour, D = 35%, M = 10%; p < 0.001), arterial pressures (mean arterial pressure at 1 hour, D = 31%, M = 7%; p < 0.001), and left ventricular stroke work index (at 1 hour, D = 75%, M = 45%; p < 0.05). Group M had greater decreases in mean pulmonary capillary wedge pressure (at 1 hour, D = -3%, M = -14%; p < 0.05). Comparisons of adverse events showed that dobutamine was associated with a higher incidence of hypertension (D = 40%, M = 13%; p < 0.02) and change of rhythm from sinus to atrial fibrillation (D = 18%, M = 5%; p < 0.04). Milrinone was associated with a higher incidence of sinus bradycardia (D = 2%, M = 13%; p < 0.03). CONCLUSIONS: Milrinone and dobutamine are appropriate and comparable for the pharmacologic treatment of the low- output syndrome after cardiopulmonary bypass.
OBJECTIVE: To analyze the relationship among Holter electrocardiogram (ECG) recordings, hemodynamic measurements indicative of global myocardial oxygen balance, and serum cardiac troponin I concentrations (cTnI) in the early postoperative period after coronary artery bypass graft (CABG) surgery. DESIGN: Prospective observational study. SETTING: University teaching hospital. PARTICIPANTS: Thirty patients undergoing CABG surgery. INTERVENTIONS: ECG measurements consisted of Holter and standard ECG recordings. Hemodynamic measurements included heart rate, systolic and diastolic blood pressure (SBP, DBP), pulmonary capillary wedge pressure, and cardiac index (CI). Derived indices included tension time index (TTI), rate-pressure product, pressure work index (PWI), and endocardial viability ratio (EVR). Serial measurements of cTnI concentrations were measured postoperatively; the area under the cTnI concentration time curve was calculated for each patient (AUC cTnI). MEASUREMENTS AND MAIN RESULTS: Episodes of myocardial ischemia were associated with small but significant rises in SBP (p = 0.01), DBP (p = 0.001), and TTI (p = 0.005) compared with periods without ischemia in the same patients. Serum cTnI concentrations 24 hours after cardiopulmonary bypass (p = 0.03) and AUCcTnI (p = 0.01) values were greater in patients who developed ECG myocardial ischemia compared with patients who did not. CONCLUSIONS: The small changes in hemodynamics seen, although statistically significant, are unlikely to be the primary cause of the ischemia. They more likely reflect an independent process that causes or occurs as a result of ischemic episodes. Ischemic episodes detected by the Holter monitor are associated with significant release of cardiac troponin from the myocardium.
OBJECTIVE: To conduct a survey of current cardiac anesthetic practice in Europe and the United States, as a first step toward establishing guidelines for the management of perioperative hypertension. DESIGN: Prospective, multicenter study. SETTING: University hospitals. PARTICIPANTS: Unselected patients (n = 1,930) requiring cardiac surgery. INTERVENTIONS: Data extending from the preoperative evaluation to 120 hours or more after surgery were collected from all patients. MEASUREMENTS AND MAIN RESULTS: Only the data from patients undergoing coronary artery bypass surgery, valve surgery, or combined procedures were analyzed, leaving a final total of 1,660 patients from the original 1,930. Of these, 88% were treated at least once perioperatively to lower arterial blood pressure. Deepening of anesthesia was the most commonly used antihypertensive measure (68%), regardless of the ongoing anesthetic regimen, and was usually combined with vasodilator therapy, most frequently nitroglycerin (53%) or sodium nitroprusside (28%). Reported perioperative mean arterial pressure (MAP) was 15 to 20 mmHg lower than MAP before anesthesia induction, regardless of the use of antihypertensive therapy. The MAP at which antihypertensive treatment was initiated varied markedly among the various phases of surgery and showed no clear correlation with preoperative MAP. CONCLUSIONS: The results of this survey show that current anesthetic practice tries to prevent perioperative hypertension wherever possible during cardiac surgery. Blood pressure measurements taken before surgery have little influence on the development of hypertension intraoperatively, and the main determinants of perioperative blood pressure control and the need for therapeutic intervention are factors arising from the surgical procedure itself, such as aortic cross-clamping and activation of adrenergic mechanisms.
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We have compared three types of high frequency jet ventilation (HFJV) with conventional positive pressure ventilation in patients recovering from elective coronary artery bypass surgery. Twelve patients were allocated randomly to receive HFJV at ventilatory frequencies of 60, 100, 150 and 200 bpm from a standard jet ventilator at either the proximal or distal airway (HFJV.p and HFJV.d), or from a valveless high frequency jet ventilator acting as a pneumatic piston (VPP). Trapped gas volume (Vtr), cardiac index (CI) and right ventricular ejection fraction (RVEF) were measured. Vtr was related to the type of HFJV used (P < 0.05) and ventilatory frequency (P < 0.05). CI decreased with increasing rate of HFJV (P < 0.05) and there were significant differences between the three types of HFJV (P < 0.05). RVEF showed a linear relationship with ventilatory frequency (P < 0.05) decreasing most with the VPP. The decrease in RVEF was associated with an increase in right ventricular end-systolic volume (P < 0.05) suggesting that an increase in right ventricular afterload was the cause. The same three types of HFJV were compared using a lung model with variable values of compliance and resistance, to assess the impact of lung mechanics on gas trapping (Vtr, ml). Lung model compliance (C) was set at 50 or 25 ml cm H2O-1 and resistance (R) at 5 or 20 cm H2O litre-1 s, where values of 50 and 5, respectively, are normal. Vtr increased with ventilatory frequency for all types of jet ventilation (P < 0.05), varying with the type of jet ventilation used (P < 0.05).
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I.v. anaesthetic agents, including propofol, have not been shown to inhibit hypoxic pulmonary vasoconstriction (HPV). This may encourage the use of propofol in thoracic surgery where one lung ventilation (OLV) is required. We have compared the effects of maintaining anaesthesia with either isoflurane or propofol infusion on right ventricular function and shunt fraction. We studied 10 patients who received isoflurane and 12 who received propofol. When OLV commenced there was a greater reduction in both mean cardiac index (3.2 (SEM 0.2) to 2.4 (0.1) litre min-1 m-2 for propofol, and 3.4 (0.2) to 3.3 (0.4) litre min-1 m-2 for isoflurane) and right ventricular ejection fraction (0.45 (0.03) to 0.37 (0.02) for propofol, and 0.48 (0.02) to 0.42 (0.02) for isoflurane) in patients who received propofol. Furthermore, these reductions were sustained for longer in the propofol group. However, propofol was not associated with a significant increase in shunt fraction during OLV, which increased threefold in patients who received isoflurane.
Nasal intermittent positive-pressure ventilation (NIPPV) has been used for domiciliary ventilatory support, and to avoid intubation for acute respiratory failure in patients with chronic airflow limitation (CAL). Its role in weaning patients from assisted ventilation in intensive care has not been defined. We have used NIPPV to wean 14 patients with respiratory disease who were referred either because of predicted difficulty in weaning or failure to wean using standard techniques. Twelve patients were ventilated for acute respiratory failure; eight patients had CAL and four had chest wall or neuromuscular disease. Two further patients with chest disease were difficult to wean following surgery. Weaning was successful in 13 patients. NIPPV corrected hypoxia, reduced hypercapnia and was well tolerated. Weaning from NIPPV was achieved in all patients with CAL, although three patients with chest wall disease later required domiciliary ventilatory support. All but one of the patients survived to leave hospital. NIPPV may have an important role in weaning from assisted ventilation, particularly in patients with underlying chronic respiratory disease. This preliminary report needs to be followed by a controlled study comparing NIPPV with established weaning methods.
A prospective trial to compare the effects of the synthetic dopaminergic (DA1) agonist, fenoldopam (FEN), with sodium nitroprusside (SNP) for control of blood pressure following coronary artery bypass graft surgery was carried out in 20 patients. Patients were randomly allocated to receive either FEN or SNP when the systolic arterial blood pressure (SAP) rose above 130 mmHg. The goal of therapy was to achieve a stable control of blood pressure below 130 mmHg at a level at least 25 mmHg below the pretreatment value. Treatment was then continued for 2 hours. Hemodynamic measurements were made before treatment, after stable control of blood pressure had been achieved, and thereafter at 30, 60, and 120 minutes. Urine output, sodium, potassium, and creatinine clearance were also measured during the study. Both SNP and FEN caused a rapid and significant fall in SAP (P < 0.001) and a fall in systemic vascular resistance (P < 0.001). FEN caused an increase in cardiac index (P < 0.001) and in stroke volume (P < 0.001) in contrast to SNP. Urine output and potassium clearance fell with SNP (P < 0.05) in contrast to FEN. Thus, FEN would appear to control SAP as effectively as SNP, but may have more beneficial effects on cardiac output and some aspects of renal function.
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Isradipine has been shown to be an effective vasodilator in different vascular beds. Experimental evidence suggests that isradipine is a potent coronary vasodilator, and this is supported by clinical studies in both cardiology and cardiac surgery. Furthermore, in these studies, coronary vasodilation was not accompanied by evidence of any significant effect on cardiac contractility or conduction. It can be concluded that the cardiac effects of isradipine will ultimately prove to be beneficial in patients undergoing myocardial revascularization.