Pharmacokinetics of ciprofloxacin in ICU patients on continuous veno-venous haemodiafiltration

Objectives: To investigate the pharmacokinetics of intravenous ciprofloxacin 200 mg every 8 h in critically ill patients on continuous veno-venous haemodiafiltration (CVVHDF), one form of continuous renal replacement therapy (CRRT). Design and setting: Open, prospective clinical study in a multidisciplinary, intensive care unit in a university-affiliated tertiary referral hospital. Patients: Sis critically ill patients with acute renal failure on CVVHDF. Interventions: Timed blood and ultrafiltrate samples were collected to allow pharmacokinetics and clearances to be calculated of initial and subsequent doses of 200 mg intravenous ciprofloxacin. CVVHD was performed with 1 l/h of dialysate and 2 l/h of predilution filtration solution, producing 3 lih of dialysis effluent. The blood was pumped at 200 ml/min using a Gambro BMM-10 blood pump through a Hospal AN69HF haemofilter,. Measurements and results: Ten pharmacokinetic profiles were measured. The CVVHDF displayed a urea clearance of 42 +/- 3 ml/min, and removed ciprofloxacin with a clearance of 37 +/- 7 ml/min. This rate was 2-2.5 greater than previously published for ciprofloxacin in other forms of CRRT. On average the CVVHDF was responsible for clearing a fifth of all ciprofloxacin eliminated (21 +/- 10%). The total body clearance of ciprofloxacin was 12.2 +/- 4.3 l/h. The trough concentration following the initial dose was 0.7 +/- 0.3 mg/l. The area under the plasma concentration time curves over a 24-h period ranged from 21 to 55 mg .h l(-1). Conclusions: Intravenous ciprofloxacin 600 mg/day in critically ill patients using this form of CRRT produced adequate plasma levels for many resistant microbes found in intensive care units.

The pharmacokinetics of once-daily dosing of ceftriaxone in critically ill patients

The aim of this study was to determine the pharmacokinetic profile of the normal recommended dose of ceftriaxone in critically ill patients and to establish whether the current daily dosing recommendation maintains plasma concentrations adequate for antibacterial efficacy. Ceftriaxone at a recommended dose of 2 g iv was administered od to 12 critically ill patients with severe sepsis and normal serum creatinine concentrations. Blood samples were taken at predetermined intervals over the first 24 h and on day 3 for measurement of ceftriaxone concentrations. There was wide variability in drug disposition, explained by the presence of variable renal function and identified by the measurement of creatinine clearance. In nine patients with normal renal function, there was a high level of creatinine clearance(mean +/- S.D., 41 +/- 12 mL/min) and volume of distribution (20 +/- 3.3 L), which resulted in an elimination half-life of 6.4 +/- 1.1 h. In comparison with normal subjects, ceftriaxone clearance was increased 100%, volume of distribution increased 90% and the elimination half-life was similar. Three patients had substantially suboptimal plasma ceftriaxone concentrations. We confirm previous findings that ceftriaxone clearance in critically ill patients correlates with renal clearance by glomerular filtration. The elimination half-life is prolonged (21.4 +/- 9.8 h) in critically ill patients with renal failure when compared with previously published data in non-critically ill patients with renal failure. We conclude that in critically ill patients with normal renal function, inadequate plasma concentrations may result following od bolus dosing of ceftriaxone. Drug accumulation may occur in critically ill patients with renal failure.

Simultaneous administration of a cocktail of markers to measure renal drug elimination pathways: absence of a pharmacokinetic interaction between fluconazole and sinistrin, p-aminohippuric acid and pindolol

Aims Previous studies suggest that estimated creatinine clearance, the conventional measure of renal function, does not adequately reflect charges in renal drug handling in some patients, including the immunosuppressed. The aim of this study was to develop and validate a cocktail of markers. to be given in a single administration, capable of detecting alterations in the renal elimination pathways of glomerular filtration, tubular secretion and tubular reabsorption. Methods Healthy male subjects (n = 12) received intravenously infused 2500 mg sinistrin (glomerular filtration) and 440 mg p-aminohippuric acid (PAH; anion secretion), and orally administered 100 mg fluconazole (reabsorption) and 15 mg rac-pindolol (cation secretion). The potential interaction between these markers was investigated in a pharmacokinetic study where markers (M) or fluconazole (F) were administered alone or together (M + F). Validated analytical methods were used to measure plasma and urine concentrations in order to quantify the renal handling of each marker. Plasma protein binding of fluconazole was measured by ultrafiltration. All subjects had an estimated creatinine clearance within the normal range. The renal clearance of each marker (Mean +/- s.d.) was calculated as the ratio of the amount excreted in urine and thearea-under-the-concentration-time curve. Statistical comparisons were made using a paired t-test and 95% confidence intervals were reported. Results The renal clearances of sinistrin (M: 119 +/- 31 ml min(-1); M + F: 130 +/- 40 ml min(-1); P = 0.32), PAH (M: 469 +/- 145 ml min(-1); M + F: 467 +/- 146 ml min(-1); P = 0.95), R-pindolol (M: 204 +/- 41 ml min(-1); M + F: 190 +/- 41 ml min(-1); P = 0.39; n = 11), S-pindolol (M: 225 +/- 55 ml min(-1); M + F: 209 +/- 60 ml min(-1); P = 0.27; n = 11) and fluconazole (F: 14.9 +/-3.8 ml min(-1); M + F: 13.6 +/- 3.4 ml min(-1); P = 0.16) were similar when the markers or fluconazole were administered alone (M or F) or as a cocktail (M + F). Conclusions This study found no interaction between markers and fluconazole in healthy male subjects, suggesting that a single administration of this cocktail of markers of different renal processes call be used to simultaneously investigate pathways of renal drug elimination.

The potential of telemedicine for home nursing in Queensland

The potential for telemedicine in home nursing was examined by retrospectively reviewing the case-notes relating to home visits made by nurses in Queensland. The case-notes of 166 clients were randomly selected from 10 domiciliary nursing centres run by the Blue Care nursing organization in south-east Queensland. Two experienced community registered nurses independently undertook a retrospective review of the case-notes. Each reviewer made an independent judgement as to whether any of the home nursing visits in the episode of care could have been conducted by telemedicine. Visits requiring hands-on care were deemed to be unsuitable for telemedicine. A total of 12,630 home visits were reviewed. The median number of visits per client was 27 (range 1-722). The mean age of the clients was 72 years (range 2-93 years). A total of 1521 home visits (12%) were judged suitable for telemedicine. There was no significant difference in suitability between males (13%) and females (12%). Care interventions suitable for telemedicine were more likely to be those of a supportive, educational or review nature. Forty per cent of clients lived up to 5 km from the home nursing centre, 33% lived 5-10 km from the centre and 27% lived over 10 km from the centre. The results of the present study confirm the potential for telemedicine in home nursing in Australia.

A cost-minimization analysis of the societal costs of realtime teledermatology compared with conventional care: results from a randomized controlled trial in New Zealand

A randomized controlled trial was carried out to measure the societal costs of realtime teledermatology compared with those of conventional hospital care in New Zealand. Two rural health centres were linked to a specialist hospital via ISDN at 128 kbit/s. Over 10 months, 203 patients were referred for a specialist dermatological consultation and 26 were followed up, giving a total of 229 consultations. Fifty-four per cent were randomized to the teledermatology consultation and 46% to the conventional hospital consultation. A cost-minimization analysis was used to calculate the total costs of both types of dermatological consultation. The total cost of the 123 teledermatology consultations was NZ$34,346 and the total cost of the 106 conventional hospital consultations was NZ$30,081. The average societal cost of the teledermatology consultation was therefore NZ$279.23 compared with NZ$283.79 for the conventional hospital consultation. The marginal cost of seeing an additional patient was NZ$135 via teledermatology and NZ$284 via conventional hospital appointment. From a societal viewpoint, and assuming an equal outcome, teledermatology was a more cost-efficient use of resources than conventional hospital care.

A randomized controlled trial assessing the health economics of realtime teledermatology compared with conventional care: an urban versus rural perspective

A randomized controlled trial was carried out to measure the cost-effectiveness of realtime teledermatology compared with conventional outpatient dermatology care for patients from urban and rural areas. One urban and one rural health centre were linked to a regional hospital in Northern Ireland by ISDN at 128 kbit/s. Over two years, 274 patients required a hospital outpatient dermatology referral -126 patients (46%) were randomized to a telemedicine consultation and 148 (54%) to a conventional hospital outpatient consultation. Of those seen by telemedicine, 61% were registered with an urban practice, compared with 71% of those seen conventionally. The clinical outcomes of the two types of consultation were similar - almost half the patients were managed after a single consultation with the dermatologist. The observed marginal cost per patient of the initial realtime teledermatology consultation was f52.85 for those in urban areas and f59.93 per patient for those from rural areas. The observed marginal cost of the initial conventional consultation was f47.13 for urban patients and f48.77 for rural patients. The total observed costs of teledermatology were higher than the costs of conventional care in both urban and rural areas, mainly because of the fixed equipment costs. Sensitivity analysis using a real-world scenario showed that in urban areas the average costs of the telemedicine and conventional consultations were about equal, while in rural areas the average cost of the telemedicine consultation was less than that of the conventional consultation.

The effect of videoconferencing on the depth perception of observers

The ability of the human eye to perceive depth was measured using a specially designed instrument. Visual acuity and both monocular and binocular stereoacuity were measured when viewing the instrument directly and via a videoconferencing link. Ten subjects with an average age of 32.5 years (range 24-50) took part in the study. The group mean visual acuity using both eyes under normal test conditions was -0.04 logMAR (Snellen 6/5) compared with 0.18 logMAR (Snellen 6/10) for the video-link. The mean stereoacuity using both eyes was 37 (SD 18) under normal test conditions. When a videoconferencing link was used, the mean stereoacuity fell to 1218 (SD 1203) using one eye and to 1651 (SD 1419) using both eyes. The ability to perceive depth remotely via a video-link was significantly decreased compared with normal test conditions.

Randomised controlled trial of telemedicine for new neurological outpatient referrals

Objective-To test the hypothesis that telemedicine for new patient referrals to neurological outpatients is as efficient and acceptable as conventional face to face consultation. Methods-A randomised controlled trial between two groups: face to face (FF) and telemedicine (TM). This study was carried out between a neurological centre and outlying clinics at two distant hospitals linked by identical medium cost commercial interactive video conferencing equipment with ISDN lines transmitting information at 384 kbits/s. The same two neurologists carried out both arms of the study. Of the 168 patients who were suitable for the study, 86 were randomised into the telemedicine group and 82 into the face to face group. Outcome measures were (I) consultation process: (a) number of investigations; (b) number of drugs prescribed; (c) number of patient reviews and (2) patient satisfaction: (a) confidence in consultation; (b) technical aspects of consultation; (c) aspects surrounding confidentiality. Diagnostic categories were also measured to check equivalence between the groups: these were structural neurological, structural non-neurological, nonstructural, and uncertain. Results-Diagnostic categories were similar (p>0.5) between the two groups. Patients in the telemedicine group had significantly more investigations (p=0.001). There was no difference in the number of drugs prescribed (p>0.5). Patients were generally satisfied with both types of consultation process except for concerns about confidentiality and embarrassment in the telemedicine group (p=0.017 and p=0.005 respectively). Conclusion-Telemedicine for new neurological outpatients is possible and feasible but generates more investigations and is less well accepted than face to face examination.

Telemedicine and developing countries - successful implementation will require a shared approach

Telemedicine is often proposed as a solution to certain health-care problems in the developing world. There seems to be little published experience on which to make judgements. A literature search revealed 39 articles, of which only two related to any kind of direct clinical work; most of them were review articles or editorials. The majority of the work reported was educational in nature, and there has been little clinical experience. It seems probable that telemedicine can help with the education of health-care workers and patients; it seems likely that it could bring major benefits to the organization of health-care. Without proper trials, it will be impossible to determine the place of health-care in the developing world. Trials are the only way in which rational decisions can ultimately be reached regarding whether scarce resources should be devoted to telemedicine in developing countries, or whether they should be employed in more conventional health-care measures whose outcomes are known to be cost-effective.