Enhancing liver blood flow after cardiopulmonary bypass: the effects of dopamine and dopexamine.

Liver blood flow is reduced after cardiopulmonary bypass (CPB) and both dopamine and dopexamine are used to overcome this. This study compares the effects of these agents on liver blood flow. Thirty patients undergoing elective coronary artery bypass graft surgery were randomized into three groups (n = 10 per group). Six hours after surgery baseline liver blood flow was determined by the percentage disappearance rate of indocyanine green measured by dichromatic auricular densitometery. Patients then received infusions of either: (1) placebo (dextrose 5%); (2) dopamine (4 micrograms/kg/min); (3) dopexamine (1 microgram/kg/min increasing to 2 micrograms/kg/min). One hour after infusion, liver blood flow measurements were repeated. In the dopexamine group the infusion was increased and the measurements repeated another hour later. We found that patient-specific variables and operative details were similar for all groups. Postoperative cardiac index and heart rate were increased significantly by dopamine (cardiac index 2.82 +/- 0.46 l/m/m2 vs 3.28 +/- 0.67 l/m/m2: p < 0.001 and heart rate 87.5 +/- 13.2 vs 96 +/- 16: p < 0.05) and dopexamine at 2 micrograms/kg/min (cardiac index 2.71 +/- 0.53 l/m/m2 vs 3.45 +/- 0.67 l/m/m2: p < 0.05 and heart rate 89.0 +/- 18.9 vs 107.4 +/- 13.6: p < 0.001) compared to placebo (cardiac index 2.97 +/- 0.8 l/m/m2 vs 3.18 +/- 0.9 l/m/m2: p > 0.05 and heart rate 77.2 +/- 7.4 vs 77.3 +/- 8: p > 0.05) despite similar atrial and systemic arterial pressures. The disappearance rate of indocyanine green was not altered during infusion of placebo group (9.0 +/- 3.2%/min vs 7.9 +/- 3.0%/min: p > 0.05) or dopexamine at 1 microgram/kg/min (9.7 +/- 3.1%/min vs 11.2 +/- 4.1%/min: p > 0.05). The disappearance rate was increased with dopamine (6.7 +/- 3.7%/min vs 11.8 +/- 3.0%/min: p < 0.05) and dopexamine 2 micrograms/kg/min (9.7 +/- 3.1%/min vs 13.5 +/- 3.2%/min: p < 0.05). This indicates a 76% increase in liver blood flow with dopamine and a 38% increase with dopexamine. We conclude that dopamine 4 micrograms/kg/min and dopexamine 2 micrograms/kg/min increase liver blood flow, although this may, in part, be related to an increase in cardiac output. Dopexamine shows no advantage over dopamine in enhancing liver blood flow after CPB.

Enzymatic debridement for necrotic wounds.

In a randomised, double-blind, controlled trial, a comparison was made of the relative efficacy of using streptokinase/streptodornase (Varidase) in a hydrogel (KY Jelly) or the hydrogel alone in the debridement of Grade IV pressure sores. Seventeen subjects aged 57-94 years (mean age 81) took part; 21 sores were studied, 11 of which were randomised to the enzyme treatment regime. Both treatments led to eschar removal; fewer days were needed in the hydrogel-only group (mean 8.1 days, sd 1.8) compared to the enzyme/hydrogel group (mean 11.8 days, sd 2.9), but this was not statistically significant. The results suggest that the use of hydrogel alone may be a cost-effective alternative to the use of streptokinase/streptodornase and hydrogel in the treatment of these wounds.

In vitro dissolution studies on nifedipine capsules.

The in vitro dissolution rates of 5 and 10 mg nifedipine capsules from eight suppliers were measured in simulated gastric fluid using the rotating paddle apparatus. A total of fourteen products were tested and the performance was found to be satisfactory for all products (> 80% dissolution in 20 min).

A drug usage review of omeprazole.

A drug use review of omeprazole was carried out at two centres in the Yorkshire Region from December 1990 to April 1991. Data collection documents were used and 66 patients in total were audited. Thirteen patients (19.7%) were treated for indications outside the product licence and 18 patients (27.3%) were treated for longer than 8 weeks. Twenty-eight patients (42.4%) received 40 mg daily. Fifty-one patients (77.3%) had received previous therapy with H2-receptor antagonists and in 33% of these patients it was at an inadequate dose or for an inadequate period of dosing or both. The results indicate a need for a prescribing policy for omeprazole.

Variations among rheumatologists in prescribing and monitoring of disease modifying antirheumatoid drugs.

One hundred consultant rheumatologists were sent a questionnaire on their prescribing pattern, and dose and monitoring schedules of four disease modifying antirheumatoid drugs (DMARDs). Seventy-five completed questionnaires were received. Sulphasalazine was the most popular first choice DMARD. There was general agreement on dose schedules which were similar to those recommended in the data sheets although for each drug a minority used different dose schedules. There was, however, marked variation among respondents in what was accepted as an adequate trial of therapy, in monitoring schedules and in the interpretation of results of toxicity monitoring. In many cases these practices differed significantly from the data sheet recommendations. These differences in stated practice could have financial and medicolegal as well as clinical implications.

A long-term prospective assessment of home nebulizer treatment.

Forty-nine patients (15 asthma, mean FEV1/FVC 1.3/2.1; 34 COPD, mean FEV1/FVC 0.7/1.8) were referred for consideration of home nebulizer treatment. All were monitored for 2 weeks while using their usual inhaled treatment followed by 2 weeks using a 'Nebuhaler' spacer to deliver 1 mg of terbutaline and 80 micrograms of ipratoropium bromide (IB) four times daily. They then borrowed a System 22 nebulizer to self-administer salbutamol nebulizer solution (5 mg), IB unit dose vials (0.5 mg) or a mixture of these drugs four times daily for 1 month each. Both asthmatic and bronchitic patients had a significant rise in their mean daily peak flow rate (PFR) during home nebulizer treatment (P < 0.03) and the COPD patients also had a significant PFR rise during Nebuhaler treatment (P = 0.0004). The mean daily peak flow rates (PFR 1 min-1 were: baseline 179, Nebuhaler 195, salbutamol nebulizer 200, IB nebulizer 198, mixed nebulizer 216). Four patients failed to respond subjectively or objectively to either Nebuhaler or nebulizer treatment. Five patients responded well to Nebuhaler treatment and did not proceed to a home nebulizer trial. Eight further patients preferred Nebuhaler to nebulizer treatment or could not tolerate nebulizer treatment (two cases). Thirty-two patients requested home nebulizer treatment for long-term use (nine salbutamol, five IB, 18 mixture). Twenty-seven of these patients had an increased mean daily PFR (compared to their usual therapy) while using their chosen nebulized treatment. The mean increase in PFR for all 32 patients was 191 min-1 (11%).(ABSTRACT TRUNCATED AT 250 WORDS)

Inappropriate digoxin monitoring.

The digoxin therapeutic drug monitoring service was evaluated during a 7-week period at Leeds General Infirmary. Data were collected for 88 patients who had one or more assays performed. The requesting clinician was contacted for each assay, and a questionnaire completed. Results were assessed to determine the appropriateness of the assay request and the action taken following receipt of the result. During the assessment period, 113 serum digoxin assays were requested. Data were collected for 88 (78%) of these, of which 22 (25%) were considered to have met all the criteria for an appropriate assay request and subsequent action. A total of 66 (75%) serum digoxin assays were assessed as wasted. The digoxin therapeutic drug monitoring service is used inappropriately at Leeds General Infirmary.

A double blind placebo controlled trial of recombinant tissue plasminogen activator in the treatment of digital ischemia in systemic sclerosis.

The treatment of digital ischemia in systemic sclerosis remains inadequate. We report a double blind, placebo controlled trial of recombinant tissue plasminogen activator (rtPA), a potent thrombolytic agent. Ten patients received rtPA. A potent, acute fibrinolytic effect was observed. During the infusion of rtPA, improvements in skin blood flow were seen. These improvements were shortlived.

High-performance liquid chromatographic determination of ciprofloxacin in plasma.

This paper describes an accurate, specific and sensitive high-performance liquid chromatographic (HPLC) method for the determination of ciprofloxacin in small samples (0.5 ml). The samples, after pretreatment by solvent extraction, were eluted on a reversed-phase column and detected by an ultraviolet detector. The results obtained on patient samples are presented.

Home nebulizers: can optimal therapy be predicted by laboratory studies?

Twenty patients (six severe asthma, 14 chronic obstructive pulmonary disease, COPD) were referred for consideration of domiciliary nebulized treatment. A double blind laboratory assessment demonstrated similar subjective and objective responses to nebulized salbutamol (5 mg), ipratropium bromide (IB) (0.5 mg) or a mixture of these medications in both groups of patients. The patients subsequently self-administered each treatment four times daily for one month. Fourteen patients requested long-term home nebulizer treatment (three salbutamol, four ipratropium bromide, seven mixture), and nine of these had their highest domiciliary peak flow recordings during home nebulizer treatment. However, subjective and objective laboratory assessments did not clearly predict the patients long-term choice of therapy in any case. There was little overall correlation between the laboratory response and the domiciliary response to treatment (Spearman correlation coefficient; subjective score, laboratory vs. home, r = 0.27, P = 0.03; peak flow response 30 min after treatment, laboratory vs. home, r = 0.31, P less than 0.02). The hospital study was also unreliable in predicting side effects during domiciliary nebulizer use. We conclude that prospective laboratory studies are of little value in the assessment of patients for home nebulizer therapy; these assessments must be made by carefully supervised domiciliary trials of nebulized treatment.

Ketanserin: an effective treatment regimen for digital ischaemia in systemic sclerosis.

We have studied the therapeutic effects of ketanserin, a specific serotonin antagonist, on digital ischaemia in 11 patients with the CREST syndrome of systemic sclerosis. Ketanserin was administered as a bolus of 10 mg intravenously, followed by an infusion over 72 h and then oral therapy. Skin blood flow as measured by thermography, bolometry, ultrasound Doppler pulses and laser light scattering, showed significant improvement. There was also marked clinical improvement with a reduction in the pain and healing of digital ulceration. These improvements were maintained on oral therapy. In 7 patients detailed studies were performed comparing oral and intravenous ketanserin therapy. When ketanserin was administered as a bolus 10 mg intravenous dose, followed by an infusion at 2 mg/h, steady state was reached by 12 h. Following oral treatment (40 mg tds) therapeutic blood levels were achieved.

Prescribing and monitoring heparin.

Aspects of heparin prescribing to include indications, dosing, administration and monitoring were investigated in 27 patients. Prescribing practices for heparin were investigated by interview of 28 physicians. Many inconsistencies in heparin prescribing were identified and monitoring was found to be haphazard.

Patient understanding of the causes and medical treatment of rheumatoid arthritis.

One hundred patients with a diagnosis of rheumatoid arthritis (RA) of more than 6 months' duration were interviewed to assess their knowledge of the disease and its treatment. Only 46 patients said they had received information about their RA from health-care professionals. The most popular source of information used by the patients was television (82%). Patients' beliefs of factors which cause RA and cause flare-ups of disease were numerous. These included stress, exercise, infections and climatic factors. Patients' knowledge of disease symptoms was incomplete. Fifty-eight patients had tried non-prescribed remedies for RA but 70% found these ineffective. Patients wanted more information about their disease and its management. Specifically considering drug treatment, 72 patients said information should be provided in leaflets.

Patient knowledge of cardio-respiratory drugs.

Eighty-five patients were interviewed to determine their knowledge of their prescribed medicines, the dosing changes they made, the action taken if adverse effects occurred and their information requirements. Most (85%) knew the reason for use of their medicines and many (73%) knew the frequency of use, but few had been told the anticipated duration of use (16%) or been warned of adverse effects (8%). Patients changed the doses of 34% of medicines as they felt appropriate. Forty patients (47%) considered they had experienced side-effects, and 42% of all patients did not disclose their adverse effect. Fifty-eight patients (68%) posed questions about their treatment. These questions concerned efficacy or indication (38%), side-effects (26%), dosing instruction (20%), duration of treatment (18%) and miscellaneous topics (29%).

Failure of intraarticular ceftazidime in a patient with Pseudomonas aeruginosa septic arthritis.

This report describes a patient with Pseudomonas aeruginosa septic arthritis who received ceftazidime by the intravenous and intraarticular routes. Concentrations of ceftazidime in the synovial fluid following both routes of administration were measured and found to be above the minimum inhibitory concentration. Despite this the organism was not eradicated. We were unable to find other literature describing the disposition of ceftazidime in synovial fluid and therefore this single-patient study provides novel information. We were unable to account for the apparent failure of therapy.

The prescribing of chloroquine and hydroxychloroquine by consultant rheumatologists in the UK.

A questionnaire on chloroquine and hydroxychloroquine prescribing was circulated nationally to 212 consultant rheumatologists and 119 replies were analysed. Of all patients receiving second-line drugs, 10% were prescribed antimalarials, with hydroxychloroquine being used four times more frequently than chloroquine. Eighty-five per cent of rheumatologists always used the same dose of hydroxychloroquine or chloroquine. Only 5% considered patient's weight in deciding the dose. Fear of ocular toxicity was expressed by many physicians; 54% had experienced corneal deposits; 4% retinopathy and 40% believed cumulative dose determined toxicity. Much confusion existed over the necessity for and frequency of ophthalmological monitoring. Only 56% requested ophthalmological tests before commencing treatment, although 86% monitored the eyes during therapy. Other side-effects were believed to affect 1-10% of patients, with no anticipated difference between doses of 250 mg chloroquine and 400 mg hydroxychloroquine daily.