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Surviving sepsis: a systems issue
Comment
Sciepro/Science Photo Library
Surviving sepsis: a systems issue
Published Online October 26, 2012 http://dx.doi.org/10.1016/ S1473-3099(12)70263-3 See Articles page 919
For more on World Sepsis Day see http://www.world-sepsisday.org/
898
In The Lancet Infectious Diseases, Mitchell M Levy and colleagues1 present an analysis of the Surviving Sepsis Campaign (SSC) database of 25 375 patients with severe sepsis or septic shock admitted to 107 intensive care units (ICUs) in the USA and 79 in Europe between 2005 and 2010. The investigators identified important international differences in processes and outcomes of care, which, taken together, provide a convincing argument for the need to address variation in structure and process to reduce mortality from this lethal and complex disease. Their results show that more patients in Europe were admitted to ICUs from ordinary wards (51·5%) than from emergency departments, whereas in the USA, more patients were admitted from emergency departments (65·1%). The median length of stay in hospital before ICU admission was longer in Europe than in the USA (1·0 vs 0·1 days; difference 0·9, 95% CI 0·8–0·9). Severity of illness (defined as the number of organ system failures), length of ICU stay and of total hospital stay, and crude mortality were all substantially greater for septic patients in Europe than for those in the USA. Patients in Europe were more likely to have a nosocomial source of sepsis and less likely to present with a urological source of infection than were those in the USA. Compliance with best practice was higher for the resuscitation bundle in the USA (6 h), and for the sepsis management bundle in Europe (24 h). The scientific evidence defining best practice at the time the data were obtained (2005–10) has been modified since in view of new findings; the elements of the initial resuscitation bundle have stood the test of time rather better than those of the sepsis management bundle. Most of the benefit of antimicrobial drugs and supportive treatment can come in the early phases of sepsis treatment. The greater proportion of patients admitted from emergency departments directly to ICUs in the USA might be a result of early direct referral to intensive care, instead of keeping patients under the care of non-intensive care specialists in ordinary wards until they have attained a severity of illness that mandates their admission to limited ICU resources as seems to happen in Europe. Compliance with the resuscitation bundle in the USA could therefore be regarded as a surrogate for a more effective front-door
emergency system and easier access to better-resourced intensive care, whereas compliance with the sepsis management bundle in Europe might represent more expert intensivist-led care once in the ICU. In other words, bundle compliance might be a health systems measure as much as it is an indicator of performance of individual clinicians, and what this study has glimpsed is the gap between islands of (comparative) excellence. Adjustment for severity of illness removed much of the extra mortality in patients in Europe compared with the USA, suggesting the possibility that clinical care was delivered as competently in Europe as in the USA, but that patients reached the ICU later (median 2 days) in Europe than in the USA and were therefore sicker with a higher mortality risk. This finding again is not new, but it surely supports the arguments that standardised mortality ratios are not necessarily a good measure of health-care adequacy or quality,2 and that improvements in outcomes from a disorder such as sepsis, which has so many different presentations, require a systems-wide human factors approach to quality improvement3 combined with awareness-raising initiatives such as World Sepsis Day. Caution must be exercised in treating world regions such as Europe as though they were homogenous entities. European SSC data will have come predominantly from ICUs in Spain and the UK, with a smaller number from Germany, Italy, and other countries. Health systems vary as much in provision of intensive care,4 physician training,5 and standards of practice6 between those countries as do those between the USA and the UK.7,8 Variation is useful for hypothesisgeneration, and this analysis of the SSC database provides an important stimulus for prospective research enquiry into the effects of resource constraints and traditions of clinical practice on treatment pathways, outcomes, and experience. The European arena may provide a valuable testing ground for the perception that outcomes of critical care are determined as much by care outside the ICU as that delivered inside. Julian Bion University Department of Anaesthesia and Intensive Care Medicine, N5 Queen Elizabeth Hospital, Birmingham B15 2TH, UK [email protected] I declare that I have no conflicts of interest.
www.thelancet.com/infection Vol 12 December 2012
Comment
1
2 3 4 5
Levy MM, Artigas A, Phillips GS, et al. Outcomes of the Surviving Sepsis Campaign in intensive care units in the USA and Europe: a prospective cohort study. Lancet Infect Dis 2012; published online Oct 26. http://dx.doi. org/10.1016/S1473-3099(12)70239-6. Lilford R, Pronovost P. Using hospital mortality rates to judge hospital performance: a bad idea that just won’t go away. BMJ 2010; 340: c2016. Bion JF, Abrusci T, Hibbert P. Human factors in the management of the critically ill patient. Br J Anaesth 2010; 105: 26–33. Adhikari NK, Fowler RA, Bhagwanjee S, Rubenfeld GD. Critical care and the global burden of critical illness in adults. Lancet 2010; 376: 1339–46. The CoBaTrICE collaboration. International standards for programmes of training in intensive care medicine in Europe. Special article. Intensive Care Med 2011; 37: 385–93.
6
7
8
Rhodes A, Moreno RP, Azoulay E, et al. Task Force on Safety and Quality of European Society of Intensive Care Medicine (ESICM). Prospectively defined indicators to improve the safety and quality of care for critically ill patients: a report from the Task Force on Safety and Quality of the European Society of Intensive Care Medicine (ESICM). Intensive Care Med 2012; 38: 598–605. Wunsch H, Linde-Zwirble WT, Harrison DA, Barnato A, Rowan KM, Angus DC. Use of intensive care services during terminal hospitalizations in England and the United States. Am J Respir Crit Care Med 2009; 180: 875–80. Wunsch H, Angus DC, Harrison DA, Linde-Zwirble WT, Rowan KM. Comparison of medical admissions to intensive care units in the United States and United Kingdom. Am J Respir Crit Care Med 2011; 183: 1666–73.
In sub-Saharan Africa, co-infection with HIV-1 and helminths is very common, affecting the natural history and disease progression of both.1 However, the effects of interaction between the two infections are a contentious issue. Findings from various studies have shown impaired immune responses against HIV in individuals with helminth infections, suggesting a role for helminths in immunity attenuation,2,3 HIV pathogenesis, and accelerated disease progression.2 However, the complex interplay between the two infections in people living in poverty hampers identification of a causal relation. The association is beset with confounding factors that complicate the design of studies to define the effects of helminth infections on HIV disease progression. These factors include the bidirectional interaction between the two infections, the effects of other bacterial and viral infectious agents, malnutrition, and possible different immunological effects of different helminth species alone and in combination.2,4,5 Despite all these complexities, and with little supportive evidence, some researchers6,7 have started advocating the treatment of helminth infections to alleviate the consequences of dual infection.7 Properly designed, randomised clinical trials showing that elimination of helminth infection reverses the immune disturbances and slows HIV progression are needed. In The Lancet Infectious Diseases, Judd Walson and colleagues report the results of a multisite, nonblinded, randomised trial to assess the efficacy of empiric deworming to delay HIV disease progression in adults who are not yet eligible for antiretroviral treatment (ART).8 Participants were recruited from three sites in Kenya where helminth prevalence is classified by the WHO as moderate.9 www.thelancet.com/infection Vol 12 December 2012
Empiric deworming did not seem to delay HIV disease progression as assessed by their primary endpoint, the proportion of people reaching a CD4 count of fewer than 350 cells per μL (p=0·2), or by their composite endpoint, which included CD4 cell count as well as time to first reported use of ART and non-traumatic deaths (p=0·1). The trial was well designed with an adequately powered sample size, it was done in three sites, had frequent deworming intervals to control re-infection, and had a long (24 month) follow-up period for assessing study outcomes, and thus appropriately addressed many of the key shortcomings of some previous trials.7 The use of both laboratory-based (CD4 cell counts, viral load) and clinical (WHO disease staging and occurrence of non-traumatic deaths) outcomes appropriately balanced the varied manifestations of HIV disease progression. Most trial participants were receiving co-trimoxazole prophylaxis and multivitamin supplements, and this approach limited the confounding effects of the role of other bacterial and protozoan infections and malnutrition on HIV disease. However, ethical concerns, as acknowledged by the authors, limited the trial from establishing baseline helminth prevalence, worm burden, and the number of individuals with infections with more than one helminth species. They used a moderate estimate of helminth prevalence that was based on a trial they previously did in the same area.10 However, only high prevalences of helminth infections and heavy worm burdens have been shown to have an adverse effect on the AIDS epidemic in Africa.1,11 In view of the heterogeneity of infection, especially in a population characterised by moderate-to-low prevalence, we believe that the absence of baseline data for helminth prevalences is a weakness of this trial
Jackie Lewin, Em Unit Royal Free Hospital/ SPL
Can deworming delay immunosuppression in HIV?
Published Online September 10, 2012 http://dx.doi.org/10.1016/ S1473-3099(12)70231-1 See Articles page 925
899
Sciepro/Science Photo Library
Surviving sepsis: a systems issue
Published Online October 26, 2012 http://dx.doi.org/10.1016/ S1473-3099(12)70263-3 See Articles page 919
For more on World Sepsis Day see http://www.world-sepsisday.org/
898
In The Lancet Infectious Diseases, Mitchell M Levy and colleagues1 present an analysis of the Surviving Sepsis Campaign (SSC) database of 25 375 patients with severe sepsis or septic shock admitted to 107 intensive care units (ICUs) in the USA and 79 in Europe between 2005 and 2010. The investigators identified important international differences in processes and outcomes of care, which, taken together, provide a convincing argument for the need to address variation in structure and process to reduce mortality from this lethal and complex disease. Their results show that more patients in Europe were admitted to ICUs from ordinary wards (51·5%) than from emergency departments, whereas in the USA, more patients were admitted from emergency departments (65·1%). The median length of stay in hospital before ICU admission was longer in Europe than in the USA (1·0 vs 0·1 days; difference 0·9, 95% CI 0·8–0·9). Severity of illness (defined as the number of organ system failures), length of ICU stay and of total hospital stay, and crude mortality were all substantially greater for septic patients in Europe than for those in the USA. Patients in Europe were more likely to have a nosocomial source of sepsis and less likely to present with a urological source of infection than were those in the USA. Compliance with best practice was higher for the resuscitation bundle in the USA (6 h), and for the sepsis management bundle in Europe (24 h). The scientific evidence defining best practice at the time the data were obtained (2005–10) has been modified since in view of new findings; the elements of the initial resuscitation bundle have stood the test of time rather better than those of the sepsis management bundle. Most of the benefit of antimicrobial drugs and supportive treatment can come in the early phases of sepsis treatment. The greater proportion of patients admitted from emergency departments directly to ICUs in the USA might be a result of early direct referral to intensive care, instead of keeping patients under the care of non-intensive care specialists in ordinary wards until they have attained a severity of illness that mandates their admission to limited ICU resources as seems to happen in Europe. Compliance with the resuscitation bundle in the USA could therefore be regarded as a surrogate for a more effective front-door
emergency system and easier access to better-resourced intensive care, whereas compliance with the sepsis management bundle in Europe might represent more expert intensivist-led care once in the ICU. In other words, bundle compliance might be a health systems measure as much as it is an indicator of performance of individual clinicians, and what this study has glimpsed is the gap between islands of (comparative) excellence. Adjustment for severity of illness removed much of the extra mortality in patients in Europe compared with the USA, suggesting the possibility that clinical care was delivered as competently in Europe as in the USA, but that patients reached the ICU later (median 2 days) in Europe than in the USA and were therefore sicker with a higher mortality risk. This finding again is not new, but it surely supports the arguments that standardised mortality ratios are not necessarily a good measure of health-care adequacy or quality,2 and that improvements in outcomes from a disorder such as sepsis, which has so many different presentations, require a systems-wide human factors approach to quality improvement3 combined with awareness-raising initiatives such as World Sepsis Day. Caution must be exercised in treating world regions such as Europe as though they were homogenous entities. European SSC data will have come predominantly from ICUs in Spain and the UK, with a smaller number from Germany, Italy, and other countries. Health systems vary as much in provision of intensive care,4 physician training,5 and standards of practice6 between those countries as do those between the USA and the UK.7,8 Variation is useful for hypothesisgeneration, and this analysis of the SSC database provides an important stimulus for prospective research enquiry into the effects of resource constraints and traditions of clinical practice on treatment pathways, outcomes, and experience. The European arena may provide a valuable testing ground for the perception that outcomes of critical care are determined as much by care outside the ICU as that delivered inside. Julian Bion University Department of Anaesthesia and Intensive Care Medicine, N5 Queen Elizabeth Hospital, Birmingham B15 2TH, UK [email protected] I declare that I have no conflicts of interest.
www.thelancet.com/infection Vol 12 December 2012
Comment
1
2 3 4 5
Levy MM, Artigas A, Phillips GS, et al. Outcomes of the Surviving Sepsis Campaign in intensive care units in the USA and Europe: a prospective cohort study. Lancet Infect Dis 2012; published online Oct 26. http://dx.doi. org/10.1016/S1473-3099(12)70239-6. Lilford R, Pronovost P. Using hospital mortality rates to judge hospital performance: a bad idea that just won’t go away. BMJ 2010; 340: c2016. Bion JF, Abrusci T, Hibbert P. Human factors in the management of the critically ill patient. Br J Anaesth 2010; 105: 26–33. Adhikari NK, Fowler RA, Bhagwanjee S, Rubenfeld GD. Critical care and the global burden of critical illness in adults. Lancet 2010; 376: 1339–46. The CoBaTrICE collaboration. International standards for programmes of training in intensive care medicine in Europe. Special article. Intensive Care Med 2011; 37: 385–93.
6
7
8
Rhodes A, Moreno RP, Azoulay E, et al. Task Force on Safety and Quality of European Society of Intensive Care Medicine (ESICM). Prospectively defined indicators to improve the safety and quality of care for critically ill patients: a report from the Task Force on Safety and Quality of the European Society of Intensive Care Medicine (ESICM). Intensive Care Med 2012; 38: 598–605. Wunsch H, Linde-Zwirble WT, Harrison DA, Barnato A, Rowan KM, Angus DC. Use of intensive care services during terminal hospitalizations in England and the United States. Am J Respir Crit Care Med 2009; 180: 875–80. Wunsch H, Angus DC, Harrison DA, Linde-Zwirble WT, Rowan KM. Comparison of medical admissions to intensive care units in the United States and United Kingdom. Am J Respir Crit Care Med 2011; 183: 1666–73.
In sub-Saharan Africa, co-infection with HIV-1 and helminths is very common, affecting the natural history and disease progression of both.1 However, the effects of interaction between the two infections are a contentious issue. Findings from various studies have shown impaired immune responses against HIV in individuals with helminth infections, suggesting a role for helminths in immunity attenuation,2,3 HIV pathogenesis, and accelerated disease progression.2 However, the complex interplay between the two infections in people living in poverty hampers identification of a causal relation. The association is beset with confounding factors that complicate the design of studies to define the effects of helminth infections on HIV disease progression. These factors include the bidirectional interaction between the two infections, the effects of other bacterial and viral infectious agents, malnutrition, and possible different immunological effects of different helminth species alone and in combination.2,4,5 Despite all these complexities, and with little supportive evidence, some researchers6,7 have started advocating the treatment of helminth infections to alleviate the consequences of dual infection.7 Properly designed, randomised clinical trials showing that elimination of helminth infection reverses the immune disturbances and slows HIV progression are needed. In The Lancet Infectious Diseases, Judd Walson and colleagues report the results of a multisite, nonblinded, randomised trial to assess the efficacy of empiric deworming to delay HIV disease progression in adults who are not yet eligible for antiretroviral treatment (ART).8 Participants were recruited from three sites in Kenya where helminth prevalence is classified by the WHO as moderate.9 www.thelancet.com/infection Vol 12 December 2012
Empiric deworming did not seem to delay HIV disease progression as assessed by their primary endpoint, the proportion of people reaching a CD4 count of fewer than 350 cells per μL (p=0·2), or by their composite endpoint, which included CD4 cell count as well as time to first reported use of ART and non-traumatic deaths (p=0·1). The trial was well designed with an adequately powered sample size, it was done in three sites, had frequent deworming intervals to control re-infection, and had a long (24 month) follow-up period for assessing study outcomes, and thus appropriately addressed many of the key shortcomings of some previous trials.7 The use of both laboratory-based (CD4 cell counts, viral load) and clinical (WHO disease staging and occurrence of non-traumatic deaths) outcomes appropriately balanced the varied manifestations of HIV disease progression. Most trial participants were receiving co-trimoxazole prophylaxis and multivitamin supplements, and this approach limited the confounding effects of the role of other bacterial and protozoan infections and malnutrition on HIV disease. However, ethical concerns, as acknowledged by the authors, limited the trial from establishing baseline helminth prevalence, worm burden, and the number of individuals with infections with more than one helminth species. They used a moderate estimate of helminth prevalence that was based on a trial they previously did in the same area.10 However, only high prevalences of helminth infections and heavy worm burdens have been shown to have an adverse effect on the AIDS epidemic in Africa.1,11 In view of the heterogeneity of infection, especially in a population characterised by moderate-to-low prevalence, we believe that the absence of baseline data for helminth prevalences is a weakness of this trial
Jackie Lewin, Em Unit Royal Free Hospital/ SPL
Can deworming delay immunosuppression in HIV?
Published Online September 10, 2012 http://dx.doi.org/10.1016/ S1473-3099(12)70231-1 See Articles page 925
899