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Biomedical subjects

J F Cade

Publications and source records attributed to J F Cade.

At least 37 records · Page 2Linked to original sources

Clinical evaluation of closed-loop control of blood pressure in seriously ill patients.

OBJECTIVE: To compare the effectiveness of a new method of closed-loop (automatic) control of BP with usual manual control. DESIGN: Within-subject crossover trial. SETTING: General and open heart ICUs in a university teaching hospital. PATIENTS: Convenience sample of 74 seriously ill patients aged 17 to 88 yr. Twenty had hypertension: postoperative (n = 7), neurologic damage (n = 6), miscellaneous (n = 7), and were prescribed nitroprusside (n = 11) or nitroglycerin (n = 9). Fifty-four had hypotension: septic (n = 33), other (n = 21), and were prescribed norepinephrine (n = 30), dopamine (n = 11), epinephrine (n = 8), or dobutamine (n = 5). An additional 21 trials were omitted from analysis because of technical (n = 7), clinical (n = 1), or drug-related problems (n = 13). INTERVENTION: Closed-loop and manual drug administrations 1-hr were studied during periods in each patient. The target and observed mean arterial pressure (MAP) and drug infusion rate were recorded electronically every 30 sec. MAIN OUTCOME MEASUREMENTS: Time taken to achieve initial control (min); fidelity of control (the integral of size and duration of error from target MAP +/- 10% in mm Hg.hr/hr); and average drug dose administered (microgram/min as % maximum possible per drug). RESULTS: Compared with manual control, closed-loop achieved faster initial control (log-rank chi 1 = 5.04, p less than .05) and greater fidelity (mean 1.37 vs. 2.36; F = 7.15, p less than .01). There was no difference in average drug dose administered. There was uniformity in the efficacy advantage of closed-loop drug administration across drugs and patient classifications. CONCLUSION: The new closed-loop system is more effective than the usual manual control in managing acute BP disturbances in the seriously ill patient.

Adolescent↗

Fluid management of shock in critically-ill patients.

This article summarizes the theoretical basis and practical applications of the fluid management of shock in critically-ill patients. It also draws attention to the differences in the aetiology and management of fluid disturbances in adult and paediatric practice. Some evidence suggests that colloidal solutions alone may be superior to crystalloid solutions alone in the resuscitation of patients with shock, but in most situations a combination of both types of fluid is more logical.

Adult↗

Thrombolytic therapy.

The accepted role for thrombolytic therapy has until recently been limited because of its complexity and side-effects. It has generally been reserved for use systemically in a limited number of patients with acute, major pulmonary embolism or iliofemoral venous thrombosis, and locally in some patients with acute, peripheral arterial occlusion. Its indications have now been greatly expanded by the confirmation from large, multicentre trials completed within the last year that it is also effective in acute myocardial infarction, with a reduction in acute mortality of 20-25%. Moreover, administration has become greatly simplified as dosage regimens have been standardised and the need for laboratory monitoring eliminated. The standard thrombolytic agent used for nearly 3 decades has been streptokinase but within the last year recombinant, human, tissue-type plasminogen activator (the first 'third generation' thrombolytic agent) has become clinically available. This protein is the body's own chief plasminogen activator and has been produced by recombinant DNA technology. Compared with streptokinase, it appears to be both somewhat more effective and also safer (less bleeding and probably no allergic reactions). Other new thrombolytic agents are also being developed but the cost-effectiveness of the newer agents in relation to streptokinase will be for many the main practical issue.

Fibrinolytic Agents↗

Comparison of ceftriaxone with cefotaxime in serious chest infections.

Ceftriaxone is a new, third-generation cephalosporin that, because of its long half-life, offers potential advantages of cost and convenience over similar agents such as cefotaxime. We compared the two drugs in a prospective, randomized study of the treatment of chest infections in seriously ill patients. Fifty-one patients (90 percent of whom were mechanically ventilated) received either ceftriaxone, 2g IV once daily, or cefotaxime, 2 g IV thrice daily, for five days. The two groups of patients appeared demographically comparable. Ceftriaxone in a single daily dose of 2 g once daily may not be satisfactory for the treatment of serious chest infections.

Adult↗

Subacute pulmonary melioidosis in a temperate climate.

Previous reports of cases of melioidosis that were seen in nonendemic areas of Australia describe recrudescences of latent infection. We describe the case of a patient who presented in the cooler climate of Melbourne with a probable primary, subacute pulmonary infection with Pseudomonas pseudomallei. This case illustrates several points that bear consideration in the management of atypical pneumonia and, more specifically, pulmonary melioidosis. Historical and occupational clues are easily missed or unrecognized, while a persistent growth of gentamicin-resistant Pseudomonas species should arouse suspicion. Septicaemic melioidosis carries a poor prognosis, and treatment should be early and aggressive; use of the newer, third-generation cephalosporin agents should be considered. Given active support in a well-equipped intensive care unit, together with appropriate antibiotic therapy, patients may eventually be cured of this infection, but a high mortality rate is still encountered.

Anti-Bacterial Agents↗

Early clinical experience of a new heparinoid, Org 10172, in prevention of deep venous thrombosis.

The potential antithrombotic effect of a new low molecular weight heparinoid, Org 10172, was examined in a randomized, double-blind, placebo-controlled, dose-ranging pilot study of the prevention of deep venous thrombosis (DVT) in 45 high-risk patients having major thoracic or abdominal surgery for cancer. Org 10172 was given in doses of 500, 750 or 1000 U bd subcutaneously. DVT occurred in 9 of 14 patients given placebo and in 4 of 11 patients given 500 U bd but in none of the 20 patients given 750 or 1000 U bd. Operative blood loss and post-operative bleeding were not significantly different between the groups but one patient given 1000 U bd had major post-operative bleeding. Average mid-interval and trough plasma anti-Xa levels reached 0.26 and 0.20 U/ml respectively following the highest dose. It is concluded that Org 10172 is a potentially useful antithrombotic agent and that the effective and safe dose appears to be between 500 and 1000 U bd for prevention of DVT in high-risk patients.

Aged↗

Prevention of lower respiratory herpes simplex virus infection with acyclovir in patients with the adult respiratory distress syndrome.

Herpes simplex virus (HSV) type I commonly occurs in the lower respiratory tract (LRT) of seriously ill patients, particularly those with the adult respiratory distress syndrome (ARDS), but it is not known whether HSV is a benign mucosal colonizer or a pathogen. The aims of this study were to determine whether the antiviral agent acyclovir could prevent this occurrence, and if so, whether prevention improved the outcome. Forty-five patients with ARDS underwent double-blind randomization into a treatment group (22 subjects) who received prophylactic acyclovir intravenously, 5 mg/kg every 8 h, and a control group (23 subjects). Upper and lower respiratory secretions were examined for the presence of HSV before randomization and twice weekly thereafter. Seven patients were excluded because of HSV detection prior to treatment. There were no significant differences between the remaining 17 acyclovir and 21 control patients in age, sex, distribution of primary diagnostic categories, and severity of primary illness. Only 1 patient (6%) in the acyclovir group developed HSV after treatment compared with 15 (71%) in the control group (p less than 0.001), but there was no improvement in the acyclovir group in the severity of respiratory failure, the duration of ventilator support (acyclovir, 20 +/- 19 days; control, 14 +/- 11 days), or mortality (acyclovir, 8 of 17, 47%; control, 9 of 21, 43%). We conclude that acyclovir is effective in preventing the high incidence of HSV in patients with ARDS, but that this prevention does not improve outcome. Routine prophylaxis of HSV is not recommended.

Acyclovir↗

Effect of aprotinin in adult respiratory distress syndrome.

The possible beneficial effect of aprotinin, a broad protease inhibitor, on the incidence and outcome of ARDS was examined in two complementary studies. In the first study, the effect of aprotinin was assessed in 147 patients admitted with multiple trauma or shock. In the 57 patients who developed ARDS, mortality was significantly less in those who had previously received aprotinin (8/20, 40%) than in those who had not (26/37, 70%). Although both treatment groups were well matched, this was a retrospective study and a second prospective, randomised, controlled study was therefore carried out. In 78 patients at risk of ARDS, there was no significant difference between treated and control patients in the incidence, duration or severity of ARDS, or in mortality or other major complications. It is concluded that aprotinin is not effective in improving any aspect of ARDS or its outcome in seriously ill patients.

Adult↗

Effects of heparin, its low molecular weight fractions and other glycosaminoglycans on thrombus growth in vivo.

Low molecular weight heparin fractions (LMWH) are less hemorrhagic but are as effective as standard heparin (SH) in preventing experimentally-induced venous thrombosis. The effect of LMWH in preventing extension of established thrombi is unknown. We have compared the effects of two LMWH's (CY, PK), and a low molecular weight heparinoid (a dermatan/heparan/chondroitin mixture, OH) with SH on the prevention of extension of established venous thrombi, by measuring their ability to inhibit the accretion of 125I-fibrin onto venous thrombi pre-formed in rabbit jugular veins. Anticoagulant activity was assayed ex vivo by the APTT and a chromogenic anti-Xa assay, and the antithrombotic effect of these glycosaminoglycans was related to their anticoagulant effects. Autologous thrombi were formed in both jugular veins of each rabbit. The rabbits were then injected with 125I-fibrinogen and treated with a bolus dose of glycosaminoglycan or saline, followed by a continuous infusion for 4 hours. All four glycosaminoglycans significantly inhibited 125I-fibrin accretion (p less than 0.001). SH, CY and PK were equipotent at doses of 42.5-62.5 anti-Xa U/kg/hr in preventing fibrin accretion by 50%. Higher doses had no further effect. OH was significantly more potent than the other three glycosaminoglycans at any given dose (p less than 0.005). There was no correlation between the antithrombotic effect and the anticoagulant effects. We conclude that these LMWH's are as effective as SH in preventing extension of established thrombosis.

Animals↗

A comparison of the antithrombotic and haemorrhagic effects of low molecular weight heparin fractions: the influence of the method of preparation.

Bleeding is an important complication of heparin therapy. A number of low molecular weight heparin fractions produce less bleeding than standard heparin for an equivalent antithrombotic effect in experimental animals. Low molecular weight heparin fractions and fragments are produced by a number of different procedures but their relative effects on haemostasis and thrombosis have not been evaluated. We have compared the antithrombotic and haemorrhagic effects of two low molecular weight heparin fragments and of a heparinoid with porcine mucosa heparin and related these in vivo findings to the results of ex vivo tests of blood coagulation and in vitro tests of platelet vivo tests of blood coagulation and in vitro tests of platelet function. Haemorrhage was assessed using a rabbit ear bleeding model. The antithrombotic effects were assessed by measuring inhibition of a tissue thromboplastin-induced jugular vein thrombus and by inhibition of fibrin and platelet accumulation in an arterial-venous shunt. The ex vivo anticoagulant effects were assessed with the thrombin clotting time, activated partial thromboplastin time and anti-Xa assay, and the effect of these glycosaminoglycans on platelet function was assessed by measuring collagen-induced platelet aggregation. For a similar antithrombotic effect, standard heparin produced significantly more bleeding than the other 3 glycosaminoglycans. The antithrombotic effects of all 4 glycosaminoglycans occurred at similar levels of anti-Xa activity but there was no relationship between blood loss and the effects of these glycosaminoglycans on any of the other tests of blood coagulation. Standard heparin had a greater inhibitory effect on collagen-induced platelet aggregation than the low molecular weight glycosaminoglycans, supporting the possibility that the increased bleeding observed with heparin is related in part to its inhibitory effect on platelet function.

Animals↗

The potential bronchodilator action of verapamil.

Although calcium antagonists such as verapamil are used primarily in cardiovascular disease, they appear to relax smooth muscle generally. Therefore, the possibility that verapamil might have bronchodilator properties was explored using the guinea-pig tracheal ring technique. Verapamil was found to produce considerable tracheal smooth muscle relaxation from a threshold concentration of 2 X 10(-7) M and with maximum effect at 10(-3) M. The responses to the contractile agonists histamine and prostaglandin F2 alpha and especially methacholine and serotonin were substantially reduced by prior administration of verapamil. Verapamil 2 X 10(-4) M was equally effective as isoprenaline 10(-8) M in producing 50% maximum direct relaxation but was more effective than isoprenaline as an antagonist of the contractile agonists, methacholine, histamine and serotonin, but not prostaglandin F2 alpha. Verapamil abolished the contractile responses to barium chloride. It is concluded that, although verapamil was not very potent as a direct bronchodilator, it could potentially be of prophylactic benefit in asthma because of its efficacy as an antagonist of common contractile agonists.

Animals↗

Intensive care--is it possible in a private hospital?

Although sophisticated intensive care units have become universal in major public hospitals in Australia, this complex and expensive form of patient care is usually not available in independent private hospitals. Such a unit was recently established in a large private hospital which had expanded its facilities to encourage major surgery and its admission policies to include complex specialist medical problems. The unit's organisation included an appropriate physical area, comprehensive equipment, skilled nursing staff, resident medical staff, accredited medical specialists, and a common set of policies and protocols. In its first 12 months, the unit had 301 admissions, 82% of whom were surgical. Unit mortality was 3.3% and hospital mortality 6%. Patients were similar in age and sex distribution to those admitted to an intensive care unit in a public hospital but their numbers, type of illness, duration of admission and mortality differed. Despite the feasibility of establishing a sophisticated intensive care unit in a private hospital, there were potential problems related to staffing (especially insufficient numbers of trained nurses), funding (especially inadequacy of hospital and medical insurance and unavailability of many drugs on the Government's Schedule of Pharmaceutical Benefits) and relations with medical staff outside the unit.

Adolescent↗

Prophylaxis of venous thrombosis after major thoracic surgery.

The high incidence (50-60%) of deep venous thrombosis of the legs (DVT) after major thoracic surgery is reduced only by about half with routine low-dose heparin prophylaxis. The present study compared the efficacy of a higher dose of heparin (7500 U twice daily) with the commonly used dose of 5000 U twice daily in preventing scan-detected DVT in 100 consecutive patients having thoracotomy for carcinoma of the lung or oesophagus. After the higher dose of heparin, postoperative DVT was not significantly less frequent (22% compared with 33% for total DVT) but was significantly less extensive (8% and 14%, respectively, for bilateral calf DVT, and 0% and 4% for popliteal DVT). Despite prophylaxis, DVT was especially common after oesophagogastrectomy (41% total DVT, 30% extensive DVT). No excessive postoperative bleeding was noted in either group. It is concluded that an increased dose of heparin safely offers increased prophylaxis against DVT in patients undergoing major thoracic surgery for cancer.

Adult↗

High risk of the critically ill for venous thromboembolism.

The incidence of deep venous thrombosis of the legs (DVT) was studied in 119 critically ill patients by 125I-labeled fibrinogen scanning; the efficacy of low-dose heparin prophylaxis was assessed in a randomized, double-blind study. DVT occurred in 29% of control patients and in 13% of patients receiving heparin 5000 U subcutaneously twice daily. DVT was found mainly in men and was associated with circulatory impairment, respiratory failure and recent vascular or cancer surgery. In a comparison study of medical patients, DVT occurred in 10% untreated and 2% treated. In conclusion, the critically ill are at high risk of venous thromboembolism and low-dose prophylaxis is warranted in those who have no hemostatic impairment.

Adult↗