Prevalence survey of healthcare-associated infections in Argentina; comparison with England, Wales, Northern Ireland and South Africa.

BACKGROUND: Prevalence surveillance methodology is the systematic observation of the occurrence and distribution of healthcare-associated infections (HCAIs) so that appropriate actions can be taken. AIM: The objectives of a prevalence survey with an international validated methodology were to determine the prevalence of HCAIs for the first time in Argentina, and to provide data which could be used for international benchmarking. METHODS: In 2008, an HCAI prevalence survey was carried out in 39 hospitals in seven of 23 provinces in Argentina, with methodology identical to that employed by the Hospital Infection Society in the third prevalence survey of HCAIs in acute hospitals in the British Isles. Data collected were processed and analysed at the Northern Ireland Healthcare-Associated Infection Surveillance Centre at Belfast. FINDINGS: A total of 4249 patients were surveyed; 480 of these had at least one HCAI, resulting in a prevalence of 11.3% of patients. Male prevalence was 13.6% and female 9.0%. The most common HCAIs were pneumonia (3.3%), urinary tract infection (3.1%), surgical site infection (2.9%), primary bloodstream infection (1.5%), and soft tissue infections (1.2%). Among the 1027 patients who underwent surgery, the prevalence of surgical site infection was 10.2%. The prevalence of meticillin-resistant Staphylococcus aureus was 1.1%, accounting for 10.0% of all HCAI isolates. The results for Argentina show higher HCAI rates compared with corresponding findings for England, Wales, Northern Ireland and South Africa. CONCLUSION: This survey will contribute to the prioritization of resources and help to inform Departments of Health and hospitals in the continuing effort to reduce HCAIs.

Four country healthcare-associated infection prevalence survey: pneumonia and lower respiratory tract infections.

In 2006, the Hospital Infection Society was funded by the respective health services in England, Wales, Northern Ireland and the Republic of Ireland to conduct a prevalence survey of healthcare-associated infection (HCAI). Here, we report the prevalence of pneumonia and lower respiratory tract infection other than pneumonia (LRTIOP) in these four countries. The prevalence of all HCAIs was 7.59% (5743 out of 75 694). Nine hundred (15.7%) of these infections were pneumonia, and 402 (7.0%) were LRTIOP. The prevalence of both infections was higher for males than for females, and increased threefold from those aged <35 to those aged >85 years (P<0.001). At the time of the survey or in the preceding seven days, 23.7% and 18.2% of patients with pneumonia and LRTIOP, respectively, were mechanically ventilated compared to 5.2% of patients in the whole study population. Meticillin-resistant Staphylococcus aureus (MRSA) was the cause of pneumonia and LRTIOP in 7.6% and 18.1% of patients, respectively (P<0.001). More patients with LRTIOP (4.2%) had concurrent diarrhoea due to Clostridium difficile compared to patients with pneumonia (2.4%), but this did not reach statistical significance. Other HCAIs were present in 137 (15.2%) of patients with pneumonia and 66 (16.4%) of those with LRTIOP. The results suggest that reducing instrumentation, such as mechanical ventilation where possible, should help reduce infection. The higher prevalence of MRSA as a cause of LRTIOP suggests a lack of specificity in identifying the microbial cause and the association with C. difficile emphasises the need for better use of antibiotics.

Hospital infection society prevalence survey of Healthcare Associated Infection 2006: comparison of results between Northern Ireland and the Republic of Ireland.

As part of the Third Healthcare Associated Infection (HCAI) Prevalence Survey of the United Kingdom and Ireland, HCAI point prevalence surveys were carried out in Northern Ireland (NI) and the Republic of Ireland (RoI). Here we explore the potential benefits of comparing results from two countries with different healthcare systems, which employed similar methodologies and identical HCAI definitions. Forty-four acute adult hospitals in the RoI and 15 in NI participated with a total of 11 185 patients surveyed (NI 3644 patients and RoI 7541). The overall HCAI prevalence was 5.4 and 4.9 in NI and the RoI, respectively. There was no significant difference in prevalence rates of HCAI, device-related HCAI or HCAI associated with bloodstream infection but there was a difference in meticillin-resistant Staphylococcus aureus-related HCAI (P = 0.02) between the two countries. There were significantly more urinary tract infections and Clostridium difficile infections recorded in NI (P = 0.002 and P < 0.001). HCAIs were more prevalent in patients aged >65 years and in the intensive care unit in both countries. HCAIs were also more prevalent if patients were mechanically ventilated, had had recent non-implant surgery (RoI) or had more recorded HCAI risk factors. This is the first time that HCAI prevalence rates have been directly compared between NI and the RoI. By closely examining similarities and differences between HCAI prevalence rates in both countries it is hoped that this will influence healthcare planning and at the same time reassure the public that HCAI is important and that measures are being taken to combat it.

Four country healthcare associated infection prevalence survey 2006: risk factor analysis.

Point prevalence surveys are useful in detecting changes in the pattern of healthcare-associated infection (HCAI). In 2004 the Hospital Infection Society was asked to conduct a third national prevalence survey, which included England, Wales, Northern Ireland and the Republic of Ireland. A similar but not identical survey was carried out in Scotland. Data were collected on standardised forms using Centres for Disease Control and Prevention definitions. This report considers associations with a wide range of risk factors for all HCAI and for four main categories. The overall prevalence rate of HCAI was 7.6% and increased significantly with age. All risk factors considered were associated with highly significantly increased risk of HCAI, except recent peripheral IV catheter and other bladder instrumentation use. Primary bloodstream infection (PBSI) was associated with antibiotic, central intravenous catheter and parenteral nutrition use. Pneumonia was associated with antibiotic, central catheter, parenteral nutrition use, mechanical ventilation and current peripheral catheter use. Surgical site infection was associated with recent surgery, antibiotic and central catheter use, mechanical ventilation and parenteral nutrition. Urinary instrumentation and antibiotic use were associated with urinary tract infection. Patients under a critical care medicine consultant had the highest prevalence of HCAI (23.2%). This report highlights those areas requiring attention to prevent HCAI, i.e. device-related infections such as PBSI (e.g. central catheters) and pneumonia (e.g. mechanical ventilation) and should influence protocols for future prevalence surveys of HCAI, e.g. the recording of risk factors at the time of assessment only is sufficient.

Four country healthcare associated infection prevalence survey 2006: overview of the results.

A survey of adult patients was conducted in February 2006 to May 2006 in acute hospitals across England, Wales, Northern Ireland and the Republic of Ireland to estimate the prevalence of healthcare-associated infections (HCAIs). A total of 75 694 patients were surveyed; 5743 of these had HCAIs, giving a prevalence of 7.59% (95% confidence interval: 7.40-7.78). HCAI prevalence in England was 8.19%, in Wales 6.35%, in Northern Ireland 5.43% and in the Republic of Ireland 4.89%. The most common HCAI system infections were gastrointestinal (20.6% of all HCAI), urinary tract (19.9%), surgical site (14.5%), pneumonia (14.1%), skin and soft tissue (10.4%) and primary bloodstream (7.0%). Prevalence of MRSA was 1.15% with MRSA being the causative organism in 15.8% of all system infections. Prevalence of Clostridium difficile was 1.21%. This was the largest HCAI prevalence survey ever performed in the four countries. The methodology and organisation used is a template for future HCAI surveillance initiatives, nationally, locally or at unit level. Information obtained from this survey will contribute to the prioritisation of resources and help to inform Departments of Health, hospitals and other relevant bodies in the continuing effort to reduce HCAI.

Prevalence surveys of healthcare-associated infections: what do they tell us, if anything?

Prevalence surveys of healthcare-associated infections offer advantages over incidence surveys, including the relative ease of performance, a reduced requirement for resources, the ability to include increased numbers of hospitals within a shorter period of time, and the possibility of more rapid data analysis and feedback. Prevalence surveys have also been shown to be useful in monitoring the effectiveness of infection control programmes. Prevalence surveys appear to be desirable when financial support, and/or the will to carry out incidence surveys, is lacking. However, it is imperative that prevalence surveys use standardised methodology and internationally recognised definitions of infection.

Survey of operating theatre ventilation facilities for minimally invasive surgery in Great Britain and Northern Ireland: current practice and considerations for the future.

Increasing use of minimally invasive surgery (MIS) and other invasive procedures has raised the question of what ventilation facilities are appropriate for such procedures to prevent infection. The Hospital Infection Society (HIS) Working Party on Infection Control in Operating Theatres undertook a survey of practice in Great Britain and Northern Ireland on the ventilation facilities provided for a variety of MIS and other procedures. Five hundred and fifty questionnaires were forwarded to HIS members, and 186 (39%) replies were received. Fifty-eight percent were from district general hospitals (DGHs). Designated theatres for orthopaedic surgery (although not necessarily ultraclean ventilated theatres) were available in more than 80% of hospitals, with approximately 50% of hospitals having designated theatres for a variety of other surgical subspecialities. Approximately two-thirds of urological procedures were performed in conventionally ventilated operating theatres. Most radiological procedures were performed in non-ventilated theatres or treatment rooms. In around half of the DGHs and university/referral hospitals, orthopaedic MIS procedures such as arthroscopy were performed in ultraclean ventilated theatres. This survey revealed considerable variation in the use of conventionally ventilated theatres and ultraclean ventilated theatres. In particular, many radiological and anaesthetic procedures are performed in treatment rooms or ventilated rooms with less than 20 air changes per hour. Whilst it is not clear whether this is acceptable practice given current knowledge, large-scale clinical trials to determine what standards of ventilation are appropriate to minimize infection for these types of procedures would be difficult to conduct. Research is needed on the relative risk of airborne infection for a variety of procedures, including whether all prosthetic implant procedures should be carried out in ultraclean ventilated theatres, as infection associated with implants is often of airborne origin and of considerable clinical significance.

Sterilization and disinfection in general practice within university health services.

A postal questionnaire on 'sterilization and disinfection' was sent to all 144 nurse members of the British Association of Health Services in Higher Education (BAHSHE). Forty-nine (34%) completed valid questionnaires were returned. Despite the majority of practices performing minor surgical procedures such as cervical cytology (N= 40, 82%), ear syringing (N= 44, 90%) and wound dressing (N= 49, 100%), only 11 (22%) had access to a sterile supply department (SSD), and the definitions of sterilization and disinfection were only identified by 23 (52%) and 14 (32%) of the respondents, respectively. Forty-one (84%) respondents had a benchtop sterilizer (30 had a benchtop sterilizer, 11 a vacuum sterilizer and two had both), although there was considerable confusion on their appropriate use and maintenance. Just over half had written procedures for sterilizer use, no practice changed the sterilizer water on a daily basis as recommended by the Medical Devices Agency (MDA), few kept a sterilizer logbook and even fewer had read the MDA Device Bulletin on benchtop sterilizers. The majority of respondents voiced an interest in attending a workshop on sterilization and disinfection. We conclude that despite the location of the general practices within an academic environment, the concept of infection control is clearly not understood by university health service staff. As the implications of a failure to implement proper infection control procedures are potentially serious, the need for adequate education and training of staff is of critical importance.

Surgical site infection surveillance.

Surgical site infection (SSI) is the third most commonly reported nosocomial infection and accounts for 14-16% of all nosocomial infections among hospital inpatients. A successful SSI surveillance programme includes standardized definitions of infection, effective surveillance methods and stratification of the SSI rates according to risk factors associated with the development of SSI. Surveillance with feedback of information to surgeons and other relevant staff has been shown to be an important element in the overall strategy to reduce the numbers of SSIs. This paper examines the essential components of a SSI surveillance system including surveillance methods, data collection and handling, analysis and presentation of results to clinical staff.

Sterilization and disinfection in general practice in Northern Ireland.

In view of the recent trend towards more minor surgery being carried out in general practice we decided to conduct a postal survey to assess the level of knowledge of sterilization and disinfection and the use of benchtop sterilizers in general practice in Northern Ireland. The survey, of all 366 practices in the Province, was carried out in January/March 1998. One hundred and eleven (30%) completed questionnaires were returned. All practices performed at least one of a range of procedures requiring sterilization or disinfection, e.g., minor surgery 95%, cervical smear taking 98%, syringing of ears 98%. Only 76% of practices had a benchtop sterilizer and 39% did not have access to a sterile supply department (SSD); 32% of the latter had no desire to utilize such a service. Only 25% and 34% correctly identified the Medical Devices Agency (MDA) definitions of sterilization and disinfection respectively. The MDA Device Bulletin on benchtop sterilizers had been read by only 26% of respondents. There was an 86% interest in attending a workshop on sterilization and disinfection. The concepts and practice of sterilization and disinfection appear not to be clearly understood. We conclude that resources must be identified to provide appropriate education in this important area for primary care staff.

Sequential antimicrobial therapy: comparison of the views of microbiologists and pharmacists.

Sequential antimicrobial therapy (SAT) is arousing keen interest in microbiologists and pharmacists. In an attempt to obtain information from these groups regarding the use of SAT in hospitals, an anonymized postal survey was carried out. A SAT questionnaire was circulated to consultant medical microbiologists, clinical microbiologists, and heads of pharmacy departments within the British Isles. Four hundred and forty-seven microbiologists and pharmacists returned completed questionnaires, giving a response rate of 29%. Just over half of medical microbiologists (MM) and pharmacists (PH) indicated that SAT was used in their institution in respiratory medicine, geriatrics, surgery and, significantly, to a lesser degree in paediatrics. The most common infections treated were pneumonia, bronchitis and wound infection. However, there were significant differences between MM and PH, with MM favouring greater use of SAT in peritonitis (P=0.03), septicaemia (P<0.01), bone infection (P<0.01), pyelonephritis (UTI) (P<0.01), and PH favouring use in bronchitis (P<0.01). The ability to take oral fluids or a recognition of no potential absorption problems were key criteria in the decision process leading to the institution of SAT by MM and PH. Significantly more MM favoured employing criteria such as temperature <38 degrees C (P<0.01), no requirement for high tissue concentrations (P=0.02) and evidence of response to i.v. antimicrobial therapy (P<0.01) than PH. The most frequently "switched" antimicrobials were metronidazole, ciprofloxacin and co-amoxiclav. There were more than five times as many MM reporting the use of clindamycin than PH (P<0.01), whereas nearly twice as many PH cited use of cefuroxime (P<0.01). Of those hospitals not employing SAT, most MM and PH concurred that the commonest reason to institute SAT was financial, followed by convenience to patients and staff. However, more PH than MM indicated that protocols (P<0.01) and a reduction in i.v. complications (P<0.01) were important to them. In promoting SAT, MM and PH felt they had the major role. Significantly, each profession felt that the other had a lesser role to play; MM as judged by the PH (P<0.01) and PH as judged by MM (P<0.01). When promoting SAT, both MM and PH felt that "education for clinicians" followed by regular audit was the best way to ensure implementation. However, significant differences arose with PH regarding nurse education (P<0.01), SAT posters (P=0.02), regular review of patients (P=0.04) and patient's notes SAT stickers (P<0.01) as more important to them than MM. Significantly, less MM than PH (P<0.01) insisted that either the i.v. and PO antimicrobials were identical or were from the same group or class when "switching". This survey highlights interesting comparisons between the approaches of MM and PH towards SAT and may indicate ways in which both groups may work together to bring about change.

Incidence and impact of Clostridium difficile infection in the UK, 1993-1996.

Questionnaires were sent to 360 UK medical microbiologists to determine the incidence of Clostridium difficile infection in the UK between 1993-1996, and to establish the current laboratory testing protocols. Replies were received from 104 laboratories (29% response rate), 86, 7, 4 and 3% of which are in England, Scotland, Wales and Northern Ireland, respectively. The laboratories serve a total of approximately 90,000 hospital beds (median 750). C. difficile testing was performed by 83% of the laboratories, and 52, 45 and 31% used toxin A +/- B kits, cell cytotoxicity, and culture +/- isolate toxigenicity testing methods, respectively. Forty-seven percent of laboratories only performed testing when specifically requested, 19% if antibiotic use was stated, 15% tested all diarrhoeal specimens, and 14% examined all specimens except those from infants and community patients. The annual totals of positive C. difficile reports and cases increased from 3132 to 12,775, and from 1576 to 8211, respectively, between 1993-1996. In 1993 C. difficile infection caused ward closures in 5% of hospitals but 16% in 1996. Antibiotic policy changes, due to C. difficile infection, occurred in 21% of hospitals in 1996 compared with only 4% in 1993. C. difficile infection appears to be increasing markedly in the UK with major implications on hospital inpatient activity. Wide variations in laboratory selection and testing methods are likely to be masking the true epidemiology of C. difficile infection, and consensus is required on optimal protocols.

Automated entry of hospital infection surveillance data.

OBJECTIVE: To assess the accuracy of an automated data entry system employing optical scanning technology and to provide an analysis of its costs as compared to manual data entry. DESIGN: The accuracy and cost of automated data entry of 100 surgical-wound infection surveillance questionnaires was compared to manual entry. SETTING: The Surgical Directorate, The Royal Hospitals, Belfast, Northern Ireland. RESULTS: The use of optical scanning technology greatly improved the speed and accuracy of data entry. The time spent by the keyboard operator on data entry was reduced substantially. For each surgical-wound infection questionnaire automatically processed, there was a saving in clerical time equivalent to $0.63. The automated data entry process resulted in a 22-fold productivity increase compared to manual data entry with validation. After validation, an error rate of < 0.2 errors per 1,000 responses was detected in automatically entered data compared to a rate of 12.4 errors per 1,000 responses for manually entered data. The automated system, including validation, provided a seven-fold productivity increase compared to "quick-and-dirty" manual data entry without validation. CONCLUSION: Hospital information technology systems may achieve total integration of data management, but realistically this would appear to be very much in the future. Until then, in view of the accuracy and substantial savings in time and money, we recommend the use of automated data entry technology. This system would be especially useful where data are transported from outlying hospitals to a central receiving center for collation and analysis.

Survey of infection in hospitals: use of an automated data entry system.

This paper describes an automated approach to data entry which substantially reduced time and effort involved in infection control surveillance within a large teaching hospital. As part of our involvement in the Second National Prevalence Survey of infection in hospitals, a hospital-wide prevalence survey of infection was carried out during January and February 1994. We simultaneously entered the results manually into an "in-house' database to enable analysis of data within the hospital. The prevalence survey was repeated during January and February 1995 using a paper questionnaire designed "in-house' and read automatically using a sheet-fed optical scanner. There was a substantial 17-fold decrease in data entry time using this method compared with manual entry. The new approach enabled more rapid analysis of surveillance data and feedback to hospital staff. If hospital clinical data is collected routinely in a format suitable for scanning, then potentially useful data could be rendered accessible. Automated data entry systems are invaluable in reducing time spent on data input and should be considered by all those involved in surveillance and audit. There would appear to be little hope in the near future of having all patient clinical data in an electronic format so that the prospects for scanning initiatives are excellent.

Death from airways obstruction: accuracy of certification in Northern Ireland.

BACKGROUND: Studies of mortality from asthma and chronic obstructive pulmonary disease (COPD) have relied on death certification or registration for case finding. The aim of this study was to determine the accuracy of death certification and registration in asthma and COPD. METHODS: All death certificates in Northern Ireland for 1987 where asthma or COPD (defined as International Classification of Diseases 9th Revision (ICD9) 490, 491, 492, 496) were listed in part I or part II were identified. The following certificates were then selected for further investigation: those mentioning asthma for all ages, those mentioning COPD for ages less than 56 years, and a 50% sample of those mentioning COPD aged 56-75 years. For these selected deaths the general practitioners' case notes, hospital records, and necropsy findings were reviewed. Questionnaires detailing the clinical history and circumstances of death were completed by the general practitioner by post and by a close relative or associate of the deceased (doctor administered) if, after initial investigation, the death was likely to be due to COPD or asthma. A panel of two respiratory physicians reviewed each death and, using clinical diagnostic criteria, assessed the accuracy of the registered cause of death. RESULTS: Of 50 registered asthma deaths 43 were confirmed as being due to asthma. In nine registered deaths from COPD in cases aged less than 56 years one was confirmed as COPD, two as asthma, and six as other respiratory conditions. Of 105 registered deaths from COPD in cases aged 56-75, 42 were confirmed as COPD, 27 as asthma, eight as other respiratory conditions, and 28 as other causes. Although few errors in registration were found, 21% of certificates mentioning asthma and 38% of certificates mentioning COPD but not asthma in part I were subject to variable application of the classification rules by the registering officers. For all deaths under 75 years of age in Northern Ireland in 1987 where either asthma or COPD was mentioned anywhere on the death certificate, the estimated sensitivity and specificity of the registered cause of death in predicting the "true" cause of death were 29% and 98.6% for asthma and 69% and 70% for COPD. CONCLUSIONS: In a population of subjects where asthma or COPD was mentioned anywhere on the death certificate, the registered cause of death is a relatively poor indicator of the "true" cause of death for both asthma and COPD. Variation occurred in the application of death classification rules by registration officers. Many deaths certified and registered as COPD could have been called asthma using current standards of clinical diagnosis. In studies investigating risk factors for deaths from asthma, case finding should consider deaths registered as COPD.

The Second National Prevalence Survey of infection in hospitals--overview of the results.

This study was designed to assess the overall prevalence of infection among the patients in hospitals in the UK and the Republic of Ireland. Patient data were collected and entered directly into a portable Olivetti (A12 notebook) computer with a custom-designed program (Epi-Info version 5.01). The statistical analysis was performed using the Statistical Package for Social Sciences software (SPSS). In all, 37,111 patients from 157 centers were studied, and a mean hospital acquired infection (HAI) prevalence rate of 9.0% (range 2-29%) was calculated. HAI rates were higher in teaching hospitals (11.2%) than in non-teaching hospitals (8.4%) P < 0.001. Four major sites of infections--infections of the urinary tract (23.2%), surgical-wound infections (10.7%), lower-respiratory tract (22.9%) and skin infections (9.6%)--accounted for 66.5% (2559 of 3848) of the total infections identified.

The second national survey of infection in hospitals: methods of data collection and overall impressions.

The Hospital Infection Society, in association with the Public Health Laboratory Service and the Infection Control Nurses Association, launched the Second National Prevalence Survey of Infection in Hospitals in 1993. On completion of the survey, 157 hospitals throughout the British Isles had taken part with approximately 37 000 patients surveyed. The survey in the Royal Hospitals Trust, Belfast, included all inpatients who were present in the wards on the survey day. Infection control nurses (ICNs) from a selected number of the other participating hospitals were sent questionnaires and asked about their methods of data collection, and their overall impression of the Second National Survey. All respondents received help in performing the survey, but only 10% provided prior training to ward staff before the survey visit. Sixty-five percent of respondents supplied information to the wards prior to the survey visit. In comparison with the questionnaire respondents, it was found that using a 'link' nurse to assist in data collection was much more efficient in relation to the time involved. Many ICNs expressed concern over the amount of time spent on this survey, although in general the value of such a survey was appreciated. Twenty-six percent of respondents indicated that they would not be willing to undertake a future survey.

An assessment of the hidden and total antibiotic costs of four parenteral cephalosporins.

The aim of this study was to compare the hidden costs, and their impact on total antibiotic costs, of ceftriaxone therapy with those of cefotaxime, ceftazidime and cefuroxime in nosocomial infection. The total antibiotic costs of 7-day standard courses of the 4 cephalosporins were compared. The costs were divided into 3 parts: (i) the cost of the drug itself; (ii) the preparation and administration (labour) costs; and (iii) the consumables and waste costs. The latter 2 costs together comprised the hidden cost of an antibiotic course. Hidden costs were higher for cefotaxime, ceftazidime and cefuroxime, which are normally administered 3 times a day, than for ceftriaxone, which is administered once daily. The percentage contribution of hidden costs to total antibiotic costs increased with decreasing antibiotic cost, and were lower with higher dosages of all antibiotics. With cefotaxime, ceftazidime and cefuroxime, and with ceftriaxone at the lower dosage given by bolus intravenous (IV) injection, the labour component of hidden costs exceeded the consumables/waste component. However, when costs were calculated for ceftriaxone administered at the higher dosage by IV infusion, the costs of consumables and waste were greater than the labour costs. Ceftriaxone had the lowest hidden costs of all the antibiotics studied. The total antibiotic cost of low dosage ceftriaxone (1 g per dose) was comparable with that of cefuroxime, and was substantially less than the costs of cefotaxime and ceftazidime. At the high ceftriaxone dosage (2g per dose), the total antibiotic cost of cefuroxime was less than that of ceftriaxone; however, the total antibiotic cost of ceftriaxone remained substantially less than that of cefotaxime or ceftazidime.

Systemic effects of salbutamol and salmeterol in patients with asthma.

BACKGROUND: Knowing the extent of the systemic effects of a new beta 2 agonist relative to an established drug is important for the prediction and interpretation of side effects. A recent study in which the effect of cumulative doses of salbutamol was compared with single doses of salmetreol suggested that, weight for weight, salmeterol may be up to 10 times more potent than salbutamol. This current study was designed to investigate further the dose equivalence of salmeterol and salbutamol. METHODS: Twelve patients with mild asthma inhaled cumulative doses of placebo, salmeterol 25, 50, 100, and 200 micrograms, and salbutamol 100, 500, 1000, and 1000 micrograms on separate days at hourly intervals in a randomised double blind crossover study. Changes in forced expiratory volume in one second (FEV1), heart rate, plasma potassium concentration, systolic and diastolic blood pressure were measured. Dose equivalence was determined as the dose ratio of salmeterol to salbutamol for the 50% maximum response to salbutamol. RESULTS: No important changes occurred in any measurements following placebo. Salmeterol and salbutamol caused a near maximum increase in FEV1 following the first dose so the dose equivalence for the airway effects could not be estimated. Heart rate increased and plasma potassium concentration and diastolic blood pressure decreased in a dose dependent manner following salmeterol and salbutamol, with median dose equivalences for salmeterol compared with salbutamol of 17.7, 7.8, and 7.6, respectively. CONCLUSIONS: These results confirm that the systemic activity of salmeterol compared with salbutamol is higher than would be expected from in vitro data, particularly for heart rate. Whether this is because of the relatively high dose of salmeterol used or pharmacokinetic differences between the two drugs is uncertain.