Rapid Responses to:
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Rapid Responses: Rapid Responses published:
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Diagnosis and management of sepsis - at the bedside
- Lindsay EM Reid (8 November 2007)
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Our experience in the management of sepsis
- Belkys Rodriguez Llerena, Marcos Iraola, Florencio Pons, Eddy Pereira, Luciano Núñez, Argelio Santana (11 November 2007)
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Don’t overlook supportive therapy for sepsis
- Akashdeep Singh, Robert James,Christian Medical College and Hospital Ludhiana,India; Rupinder kaler,Christian Medical College and Hospital Ludhiana,India; Jaspreet Singh NYU Medical Centre New York (13 November 2007)
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Human recombinant activated protein C for severe sepsis
- Georgia Salanti, Andrés Cardona, Arturo Martí-Carvajal (16 November 2007)
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Steroids in sepsis
- Iain D Drummond (19 November 2007)
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Predicted, Ideal or Actual Body Weight ?
- M Samer Abdalla (3 December 2007)
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Re: Predicted, Ideal or Actual Body Weight ?
- Iain M Mackenzie, Andrew Lever (3 December 2007)
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Lindsay EM Reid, FY2 Western General Hospital, Edinburgh, EH4 2XU
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MacKenzie and Lever have described the definition, epidemiology, diagnosis, and now management of sepsis in some detail. As a junior doctor who is often the first to review patients in the initial stages of sepsis, and who is therefore responsible for the initial diagnosis and management, I am frequently guided by the Surviving Sepsis Campaign. This campaign was formed in 2002 to combat worsening trends in the incidence and mortality relating to sepsis1. In my clincial practice this means that if a patient exhibits 2 or more of the Systemic Inflammatory Response (SIRS) criteria (Table 1), then the 6 hour resuscitation bundle should be triggered (Table 2). The first 4 steps can be carried out immediately on the ward. There has been clear evidence for the positive impact of these interventions on morbidity and mortality relating to sepsis1,2,3. Table 1:
Table 2:
A recent audit we conducted in a district general hospital showed these interventions were not being instigated on a regular basis - in patients fulfilling criteria for sepsis, only 57% had blood cultures within 6 hours, 30% had serum lactate measured, 53% had an ABG, empirical antibiotics were administered in 80% cases and adequate fluid resuscitation was performed in 97%. Current literature would suggest that this reflects the situation on a wider scale4,5. Therefore a means for tackling failings in the diagnosis and initial management of sepsis, would be to start with better education of these simple interventions. References: 1. Poulton B (2006). Advances in the management of sepsis: the randomised controlled trials behind the surviving sepsis campaign recommendations. International Journal of Antimicrobial Agents; 27: 97 - 101 2. Houck PM, Bratzler DW, Nsa W, Ma A, Bartlett JG (2004). Timing of antibiotic administration and outcomes for Medicare patients hospitalised with community-acquired pneumonia. Archives of Internal Medicine; 164: 637 – 44 3. Rivers E, Nguyen B, Havstad S, et al (2001). Early goal-directed therapy in the treatment of severe sepsis and septic shock. New England Journal of Medicine; 345: 1368 – 1377 4. Kinsella MT, Biltoft JM, Marez H, Glaser D, Kwong N, Restrepo C (2006). Improving mortality from severe sepsis by implementation of surviving sepsis guidelines at a community teaching hospital. Critical Care Medicine; 34(12): A109 5.Ferrer R (2006). Impact of sepsis care bundles on hospital mortality in Spain. Critical Care Medicine; 34(12): A108 Competing interests: None declared |
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Belkys Rodriguez Llerena, Chief of Intensive Care Unit Hospital Universitario, Marcos Iraola, Florencio Pons, Eddy Pereira, Luciano Núñez, Argelio Santana
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We have read your interesting article about the management of sepsis and we agree with your points of view about this topic. Time is one of the more important predictors of outcome. The delay in diagnosis and the delay in treatment lead to a worse prognosis. We consider that cultures must be done once the physician thinks of sepsis and they must be taken in the emergency department and before any antimicrobial treatment in case of patients that arrive at hospital from home. In this case, the antimicrobials must be prescribe in the emergency department. In case of patients that began with nosocomial infection, the cultures must be done very fast and the antimicrobial treatment must be prescribe by the physicians in intensive care, if we are talking about severe sepsis. To select them we have to suspect the site of infection and we have to know the more common agents we have in our units. The selection depends too on the kind of infection and the comorbilities that the patients have. If we suspect stapholoccocal sepsis (frequently in skin and soft tissue infections) we prescribe vancomicyn too before receiving the results of cultures. In fluid resuscitation we prefer to use cristaloids and our guide is the central venous pressure. If we don't have an answer with these, we use dopamine infusion along or with dobutamine. We use too, small dosis of steroids. We dont have the possibility to prescribe activated C Protein, then, we dont have any experience in its use. Then, we base our treatment in support with fluids, antimicrobials, steroids, prevention of the multiple organ failure, nutrition. We must make ventilatory support and we prefer like you, enteral nutritional support. The more common causes of severe sepsis and septic shock admissions are intra-abdominal sepsis in surgery patients, enteral sepsis caused by Gram negative bacteria, skin infections by Stapholococcus aureus in many cases, intravascular sepsis. Worse outcome in our unit is seen in patients with fungal and stapholoccocal infections. Competing interests: None declared |
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Akashdeep Singh, Assist. Professor Christian Medical College and Hospital Ludhiana,India 141008, Robert James,Christian Medical College and Hospital Ludhiana,India; Rupinder kaler,Christian Medical College and Hospital Ludhiana,India; Jaspreet Singh NYU Medical Centre New York
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To the Editor: In the review article on the “Management of Sepsis”, presented by Iain Mackenzie and Andrew Lever (3 Nov. issue),1 the discussants do not mention about stress ulcer prophylaxis; lung-protective strategy ; role of heparin and threshold for correction of anemia. All of these have some role in the management of sepsis which can’t be overlooked. Several large trials confirmed the benefit of stress ulcer prophylaxis in general ICU patients including those with sepsis. [2,3] ARDS Network trial clearly showed a 9% decrease of all-cause mortality in patients ventilated with tidal volumes of 6 mL/kg of predicted body weight (as opposed to 12 mL/kg) while aiming for a plateau pressure < 30 cm H2O .[4] Patients with severe sepsis are at high risk of venous thromboembolic events (VTEs) due to one or more risk factors, including advanced age, chronic cardiopulmonary disease, recent surgery, immobilization, in- dwelling vascular catheters, and previous VTE history [5]. Indeed, VTE prophylaxis using unfractionated heparin (UFH), low molecular weight heparin (LMWH), and/or mechanical methods has become standard of care in most institutions. Despite modest prophylactic efficacy, it has been suggested that heparins may have direct therapeutic effects in severe sepsis and DIC, independent of their role in thromboprophylaxis [6]. Anemia is prevalent in critically ill adults, who as a group receive a large number of red-cell transfusions. [7] By the third day in the intensive care unit (ICU), 95% of critically ill patients have anemia, and 40 to 50% of them will receive on average almost 5 units of red cells during their stay in the ICU. TRICC & TRIPICU trial clearly demonstrated that a transfusion trigger of 7.0 g per deciliter for most critically ill adults and Pediatric appears to be appropriate in decreasing the mortality. [8,9] REFERENCES 1. Iain Mackenzie and Andrew Lever. Management of sepsis. BMJ 2007;335;929-932 2. Bresalier RS, Grendell JH, Cello JP, Meyer AA (1987) Sucralfate versus titrated antacid for the prevention of acute stress-related gastrointestinal hemorrhage in critically ill patients. Am J Med 83:110–116 3. Cook D, Guyatt G, Marshall J et al. (1998) A comparison of sucralfate and ranitidine for the prevention of upper gastrointestinal bleeding in patients requiring mechanical ventilation. Canadian Critical Care Trials Group. N Engl J Med 338:791–797 4. Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome. The Acute Respiratory Distress Syndrome Network. N Engl J Med 2000; 342:1301–1308 5. Cook DJ, Crowther MA, Meade MO, Douketis J, for the VTE in the ICU Workshop Participants. Prevalence, incidence, and risk factors for venous thromboembolism in medical-surgical intensive care unit patients. J Crit Care 2005;20:309–313. 6. Davidson BL, Geerts WH, Lensing AW. Low-dose heparin for severe sepsis. N Engl J Med 2002;347:1036–1037. 7. Corwin HL, Gettinger A, Pearl RG, et al. The CRIT Study: anemia and blood transfusion in the critically ill — current clinical practice in the United States. Crit Care Med 2004;32:39-52. 8. Hebert PC, Wells G, Blajchman MA, et al. A multicenter, randomized, controlled clinical trial of transfusion requirements in critical care. N Engl J Med 1999;340:409-17. 9. Lacroix J, Hébert PC, Hutchison JS, et al. Transfusion strategies for patients in pediatric intensive care units. N Engl J Med 2007;365:1609 -19. Competing interests: None declared |
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Georgia Salanti, Lecturer University of Ioannina School of Medicine, Ioannina 45110, Greece, Andrés Cardona, Arturo Martí-Carvajal
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The review by I. Mackenzie and A. Lever discusses, among others, the available evidence regarding the harms and benefits of the administration of human recombinant activated protein C (APC) in the management of sepsis. The authors conclude that “overall, whether the risks of drotrecogin alfa outweigh the benefits is now far from clear, even in patients with a high risk of death”. On this, we would like to add the results of a recently published systematic review of the effectiveness and safety of APC which found no evidence suggesting that it should be used for treating patients with severe sepsis or septic shock (1). The quantitative synthesis of three published studies in adults (2-4) resulted into a summary relative risk (RR) for 28-day mortality of 0.92 (95% Confidence interval (CI) 0.72 to 1.18; p-value = 0.42, heterogeneity I2 = 72.0%). The PROWESS study (2) was the only included trial to show a statistically significant benefit for APC, particularly in patients at high risk of death. This study was designed to detect a positive effect in the entire population and not in subgroups and a modification of the protocol regarding the inclusion criteria and the interventions took place halfway through the trial. The modification, which was not reported in the published article but appears in the US Food And Drug Administration report (5) seemed to divide the trial into two discernible phases in which the efficacy of APC was remarkably different. These discrepancies in the PROWESS study have previously attracted criticism (6). Ignoring the data after the modification of the protocol in the PROWESS study, the high heterogeneity between the trials disappears and the summary effect of APC in 28-day mortality was estimated RR= 1.01 (95% CI 0.89 to 1.15; p-value = 0.84). There seems to be no evidence suggesting any benefit associated with APC. On the other hand, the synthesis of the same three trials showed a higher risk of bleeding in the APC group (RR=1.47 (95% CI 1.03 to 2.09). We feel that, until well designed randomized trials provide evidence of a treatment effect, the routine use of APC in the management of sepsis is not justified. References: 1. Martí-Carvajal A, Salanti G, Cardona AF. Human recombinant activated protein C for severe sepsis. Cochrane Database Syst Rev. 2007 Jul 18;(3):CD004388. 2. Bernard GR, Vincent JL, Laterre PF, LaRosa SP, Dhainaut JF, Lopez- Rodriguez A, et al. Efficacy and safety of recombinant human activated protein C for severe sepsis. N Engl JMed 2001;344:699-709. 3. Abraham E, Laterre PF, Garg R, Levy H, Talwar D, Trzaskoma BL, et al. Drotrecogin alfa (activated) for adults with severe sepsis and a low risk of death. New England Journal of Medicine 2005;353:1332-41. 4. Bernard GR, Ely EW, Wright TJ, Fraiz J, Stasek JE Jr, Russell JA, et al. Safety and dose relationship of recombinant human activated protein C for coagulopathy in severe sepsis. Critical Care Medicine 2001;29(11):2051-9. 5. FDA 2001. FDA Briefing document: Anti-infective Advisory Committee. Drotrecogin alfa (activated)). [Recombinant human activated protein (rhAPC)]. XIGRIS™ BLA # 125029/0. September 12. http://www.fda.gov/ohrms/dockets/ac/01/briefing/3797b1_02_FDAbriefing.pdf 2001. 6. Eichacker PQ, Natanson C. Recombinant human activated protein C in sepsis: inconsistent trial results, an unclear mechanism of action, and safety concerns resulted in labeling restrictions and the need for phase IV trials. Critical Care Medicine 2003;31(1):Suppl: 94-6. Competing interests: None declared |
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Iain D Drummond, ST2 Intensive Care Medicine Queen Margaret Hospital, Dunfermline, KY12 OSU
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Mackenzie and Lever provide an excellent overview of the management of sepsis and acknowledge that the role of steroids in the management of sepsis remains uncertain. (1) They inform us that "recent meta-analyses suggest that low dose hydrocortisone...in unselected patients with severe sepsis or septic shock shock significantly reduces both the duration of shock and in-hospital mortality, without incurring additional complications". They go on to suggest that the benefits may be even greater if the steroid treatment is reserved for patients with proven adrenal insufficiency. However, a recent review article on adrenal insufficiency and steroid therapy suggested that this approach may not be feasible. (2) It pointed out that a Phase 3 trial failed to demonstrate a survival benefit in patients who failed to significantly respond to adrenocorticotrophic hormone (ACTH) who were treated with steroids. It also pointed out that there may be inaccuracies in measuring serum cortisol and hence difficulties in interpreting results. I would also like to point out that in my own hospital when attempting to perform an ACTH stimulation test prior to commencing low- dose corticosteroid therapy on a septic patient in the middle of the night no-one was able to locate any synthetic ACTH! References 1) Mackenzie I, Lever A. Management of sepsis. BMJ 2007;335:929-932 2) Thomas Z, Fraser G. An update on the diagnosis of adrenal insufficiency and the use of corticotherapy in critical illness. Annals of Pharmacotherapy 2007;41:1456-65. Competing interests: None declared |
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M Samer Abdalla, Specialist Registrar in Anaesthesia & ICM Homerton University Hospital, London E9 6SR, UK
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Dear Editors; I read with great interest the review article of management of sepsis (1) in which the authors uses the term of ideal rather than predicted body weight to prescribe the low-tidal volume ventilation in patients with acute lung injury or adult respiratory distress syndrome (ARDS). The term of predicted, body weight was used in the original ARDSNet trial (2). The Surviving Sepsis guidelines endorse low tidal-volume ventilation based on predicted body weights(3). The concept underlying this approach is that predicted rather than actual body weight normalizes the tidal volume to lung size, since lung size has been shown to depend most strongly on height and sex. For example, a person who weighed 70 kg and who then gains 35 kg has essentially the same lung size as he or she did when at a weight of 70 kg and should not receive ventilation with a higher tidal volume just because of the weight gain (2) My question is there any significant differences between calculated ideal body weight and the predicted body weight? If the answer is no could we use both terms interchangeably? (1) Mackenzie I, Lever A. Management of sepsis. BMJ 2007 November;335;929-932 (2) The Acute Respiratory Distress Syndrome Network. Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome. N Engl J Med. 2000 May 4;342(18):1301-8 (3) Dellinger RP, et al. Surviving Sepsis Campaign guidelines for management of severe sepsis and septic shock.Intensive Care Med. 2004 Apr;30(4):536-55. (4) Malhotra A, Low-tidal-volume ventilation in the acute respiratory distress syndrome. N Engl J Med. 2007 13;357(11):1113-20 Competing interests: None declared |
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Iain M Mackenzie, Consultant John Farman ICU, Addenbrooke's Hospital, Cambridge, CB2 2QQ, Andrew Lever
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In the context of body weight, acute respiratory distress syndrome (ARDS), and our review the terms 'ideal' and 'predicted' are synonymous. Competing interests: None declared |
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