E.D. Cooke

Comparison of intravenous infusions of iloprost and oral nifedipine in treatment of Raynaud's phenomenon in patients with systemic sclerosis: a double blind randomised study.

OBJECTIVE--To compare the long term effects of short term intravenous infusions of iloprost with those of oral nifedipine in patients with Raynauds phenomenon associated with systemic sclerosis. DESIGN--Double blind, placebo controlled, randomised group comparison. SETTING--Dermatology outpatient clinic. PATIENTS--Twenty three patients with Raynauds phenomenon associated with well documented systemic sclerosis (American Rheumatism Association criteria) and with typical abnormalities in fingernail folds on capillaroscopy. INTERVENTIONS--Twelve patients were randomised to receive intravenous infusions of iloprost starting at 0.5 ng/kg/min and increased by 0.5 ng/kg/min every 15 minutes to a maximum of 2.0 ng/kg/min for eight hours on three consecutive days with a further single infusion at week 8. Placebo capsules were given concurrently. Eleven patients were randomised to receive nifedipine, starting at 30 mg daily and increased to 60 mg daily after four weeks for another 12 weeks. Infusions of placebo were given in the same manner as the infusions of iloprost. One patient from each group withdrew because of social reasons and three patients receiving nifedipine withdrew because of side effects. END POINT--Reduction in number, duration, and severity of attacks of Raynauds phenomenon, reduction in number of digital lesions, increase in digital blood flow. MEASUREMENTS AND MAIN RESULTS--Measurements were taken at 0, 4, 8, 12, and 16 weeks. Both regimens produced a reduction in the number, duration, and severity of attacks of Raynauds phenomenon. The mean (SE) number of digital lesions was reduced with iloprost (from 3.5 (1.6) to 0.6 (0.3] and with nifedipine (from 4.3 (0.8) to 1.4 (0.5] after 16 weeks. Hand temperature and digital and microcirculatory blood flow were increased with iloprost but not with nifedipine. CONCLUSION--Both iloprost and nifedipine are beneficial in the treatment of Raynauds phenomenon. With nifedipine, however, side effects are common. Short term infusions of iloprost provide longlasting relief of symptoms, and side effects occur only during the infusions and are dose dependent.

Treatment of Raynaud's phenomenon by intravenous infusion of prostacyclin (PGI2)

Twenty five patients with Raynauds phenomenon due to systemic sclerosis were infused with prostacyclin (PGI2). In 88% of the patients there was objective improvement, monitored by thermography or radiometry.

Prostaglandin E1 infusions for vascular insufficiency in progressive systemic sclerosis.

Twelve patients with systemic sclerosis (SS) and severe Raynauds phenomenon received infusions of prostaglandin E1 (PGE1) at a dose of 6-10 ng/kg/min, with either saline or 5% dextrose, for 72 hours in a single-blind cross-over study. The infusions were administered intravenously by centrally positioned catheters. Infusions were well tolerated with only mild side effects. Following the PGE1 infusion cold tolerance improved and attacks of Raynauds phenomenon were less frequent, less severe, and shorter in duration. This subjective improvement was maintained for several weeks in most patients, and 2 noted healing of ischaemic ulcers. There was no significant change in objective measurements of hand function after either infusion. However, pain measured on a 10 cm visual analogue scale improved 2.19 cm with PGE1 and only 0.91 cm with normal saline (P less than 0.05). Temperature of the fingers and hands recorded by thermography did not change significantly with saline infusions, but did rise during PGE1 infusions (mean rise 2.0 degrees C at 48 hours, p less than 0.001), and was maintained when measured again 2 weeks later (mean rise 1.56 degrees C, p less 0.001). PGE1 may therefore be suitable treatment for Raynauds phenomenon and the vascular insufficiency of systemic sclerosis and other connective tissue diseases.

INTRAVENOUS LIGNOCAINE IN PREVENTION OF DEEP VENOUS THROMBOSIS AFTER ELECTIVE HIP SURGERY

Intravenous lignocaine is a possible means of preventing deep venous thrombosis (D.V.T.) after elective hip surgery. In 14 control patients the total incidence of D.V.T. was 78%, with a 57% incidence of thigh-vein thrombosis. In 14 patients treated at random with intravenous lignocaine during the first 6 postoperative days, there were only 2 calf-vein thrombi (14%; P less than 0-005). In a further 14 cases treated consecutively there were 4 unilateral calf-vein thrombi. No thrombi originated in the thigh veins (P less than 0-001). After intravenous lignocaine was stopped the total incidence of D.V.T. in the 28 patients rose to 53% with a 21% incidence of thigh-vein thrombi between the 7th and 14th postoperative days. There was no significant difference in postoperative coagulation and fibrinolytic activity between control and treated patients, and blood loss and transfusion requirements were similar. Immediate or delayed hypersensitivity reactions to lignocaine were not observed. The results support the view that damage to the vessel wall may be the initial event in the formation of a venous thrombus.

Prolonged increase in digital blood flow following iloprost infusion in patients with systemic sclerosis.

Thirteen patients with Raynauds phenomenon secondary to systemic sclerosis received three 8-hour infusions of a synthetic prostacyclin analogue (Iloprost) on consecutive days and were followed-up over a period of 10 weeks during the winter of 1985/86. Six weeks after infusion, digital peripheral vascular resistance had fallen (P less than 0.05) and dicrotic notch proportion of pulse amplitude increased (P less than 0.05). Digital blood flow and pulse amplitude (measured by photoplethymography) were also increased but did not reach statistical significance. The trend of improvement in these blood flow parameters was still evident after 10 weeks. The number of cutaneous lesions (digital ulcers, etc) fell from 26 lesions before infusion to only 7 lesions by the end of the study, confirming the subjective improvement reported by the patients.

The effect of captopril on cutaneous blood flow in patients with primary Raynaud's phenomenon

Fifteen patients with primary Raynauds phenomenon received captopril 25 mg or placebo, three times daily for 6 weeks, in a randomized double‐blind cross‐over study. Compared with placebo, captopril produced a significant improvement in cutaneous blood flow but did not alter the frequency or severity of attacks of Raynauds phenomenon.

Noninvasive measurement of the human peripheral circulation: relationship between laser doppler flowmeter and photoplethysmograph signals from the finger

Under certain conditions laser Doppler flowmeter (LDF) signals obtained from the finger pulp may appear very similar to those obtained by use of a direct current (dc) photoplethysmograph (PPG). A combined LDF/PPG system was used in conjunction with a circumference strain gauge as an index of vol ume change to identify the conditions in which the correlation between these signals was good. Simultaneous LDF and dc PPG measurements were made on 10 normal vol unteers by using arterial occlusion and on 7 normal subjects by using the Val salva maneuver at different elevations of the forearm and hand with respect to the midsternum. By altering the elevation of the upper limb the influence of venous filling on each of the signals during these maneuvers was observed. Since the dc PPG signal always appeared similar to the volume change indi cated by the circumference strain gauge, it is concluded that the dc PPG signal is related to blood volume change if allowance is made for the effects of blood oxygenation. In circumstances of low venous filling, however, blood volume changes correlate well with blood flow changes, producing the correlation be tween the dc PPG and LDF traces. The dc PPG signal may be used as a means of monitoring changes in blood flow in the finger only when venous filling is low and the return remains unre stricted. Thus, in investigations using this method, the relative position of the limb with respect to the heart should always be indicated. The LDF method appears to be a reliable indicator of blood flow changes in the microcirculation irrespective of the degree of venous filling.

Changes in Blood Flow Close to Subcutaneous Insulin Injection Sites in Stable and Brittle Diabetics

Photoelectric Plethysmography (PPG) Was Used to investigate blood flow changes closeto superficial subcutaneous injection sites. As a validation procedure, the PPG response to subcutaneous injection of a known hyperemic agent, prostaglandin E, (10−5 M), was shown to correlate strongly with subcutaneous blood flow changes estimated by the established technique of133Xe washout. Changes in blood flow over the subcutaneous injection sites of insulin (Actrapid) and insulin diluent were measured by photoelectric plethysmography in six nondiabetics and in six stable and seven brittle insulin-dependent diabetics. In all subject groups, an acute increase in local blood flow was seen within 2 min of both insulin and diluent injections, probably caused by injection trauma. At diluent injection sites, this acute hyperemia faded rapidly, blood flow returning to preinjection levels within 15–20 min, and there was no further increase in blood flow in any of the subjects. Insulin injected into the nondiabetics and stable diabetics caused a pronounced increase in local blood flow, sustained for at least 60 min after injection. In the brittle diabetics, however, there was no prolonged local hyperemia, the response being significantly less than that seen in both the nondiabetics and the stable diabetics. Insulin-related hyperemia close to injection (or infusion) sites may be important in subcutaneous insulin absorption. Its near-absence in brittle diabetics may contribute to the impaired response to subcutaneous insulin characteristic of these patients.

Photoplethysmography of the Distal Pulp in the Assessment of the Vasospastic Hand

A procedure for assessing the peripheral vasculature and a new technique for determining the characteristics of the a.c. (arterial) photoplethysmographic (PPG) waveform are described. Comparing 12 normal female volunteers and 12 female patients with Raynauds phenomenon, PPG amplitude is as good as the results of a standard thermographic test in distinguishing between the groups. The limb arterial flow measured by strain gauge plethysmography (SPG) and the timing of features in the PPG waveform showed differences between the groups, which did not reach statistical significance. The rise time of the PPG waveform, however, was found to be correlated with age independently of vasospasticity.

Non‐invasive Screening for Venous Thromboembolic Disease

Venous thromboembolism is an important cause of morbidity and mortality, and the clinical signs are notoriously unreliable. Two safe and reliable non‐invasive techniques have therefore been developed for the diagnosis of DVT namely thermography, and the measurement of serum levels of fibrinogen degradation fragment E (FgE). A total of 93 medical patients were studied using these techniques and the results were compared with the phlebographic appearances of the lower limbs. In 91 patients, the thermographic findings were identical to the radiological findings; there was one false‐positive thermograph, and one false‐negative thermograph, which occurred in a case of isolated calf vein thrombosis. There were 59 subjects without evidence of DVT only one of whom had an FgE level greater than 400 μg/l., whereas 17 of the 19 subjects with extensive DVT proximal to the knee, had levels greater than 400 μg/l. In eight subjects with clinical and perfusion lung scan evidence of pulmonary emboli, the FgE levels were all greater than 800 μg/l. These findings demonstrate the reliability of a combination of these two non‐invasive diagnostic techniques in the detection of DVT. The local lesion may be identified using thermography, whereas elevated levels of FgE indicate the likelihood of extensive thrombosis with embolization.