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      Recommendations for sepsis management in resource-limited settings

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          Abstract

          Purpose

          To provide clinicians practicing in resource-limited settings with a framework to improve the diagnosis and treatment of pediatric and adult patients with sepsis.

          Methods

          The medical literature on sepsis management was reviewed. Specific attention was paid to identify clinical evidence on sepsis management from resource-limited settings.

          Results

          Recommendations are grouped into acute and post-acute interventions. Acute interventions include liberal fluid resuscitation to achieve adequate tissue perfusion, normal heart rate and arterial blood pressure, use of epinephrine or dopamine for inadequate tissue perfusion despite fluid resuscitation, frequent measurement of arterial blood pressure in hemodynamically unstable patients, administration of hydrocortisone or prednisolone to patients requiring catecholamines, oxygen administration to achieve an oxygen saturation >90%, semi-recumbent and/or lateral position, non-invasive ventilation for increased work of breathing or hypoxemia despite oxygen therapy, timely administration of adequate antimicrobials, thorough clinical investigation for infectious source identification, fluid/tissue sampling and microbiological work-up, removal, drainage or debridement of the infectious source. Post-acute interventions include regular re-assessment of antimicrobial therapy, administration of antimicrobials for an adequate but not prolonged duration, avoidance of hypoglycemia, pharmacological or mechanical deep vein thrombosis prophylaxis, resumption of oral food intake after resuscitation and regaining of consciousness, careful use of opioids and sedatives, early mobilization, and active weaning of invasive support. Specific considerations for malaria, puerperal sepsis and HIV/AIDS patients with sepsis are included.

          Conclusion

          Only scarce evidence exists for the management of pediatric and adult sepsis in resource-limited settings. The presented recommendations may help to improve sepsis management in middle- and low-income countries.

          Electronic supplementary material

          The online version of this article (doi:10.1007/s00134-012-2468-5) contains supplementary material, which is available to authorized users.

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          Most cited references86

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          Effect of a protective-ventilation strategy on mortality in the acute respiratory distress syndrome.

          In patients with the acute respiratory distress syndrome, massive alveolar collapse and cyclic lung reopening and overdistention during mechanical ventilation may perpetuate alveolar injury. We determined whether a ventilatory strategy designed to minimize such lung injuries could reduce not only pulmonary complications but also mortality at 28 days in patients with the acute respiratory distress syndrome. We randomly assigned 53 patients with early acute respiratory distress syndrome (including 28 described previously), all of whom were receiving identical hemodynamic and general support, to conventional or protective mechanical ventilation. Conventional ventilation was based on the strategy of maintaining the lowest positive end-expiratory pressure (PEEP) for acceptable oxygenation, with a tidal volume of 12 ml per kilogram of body weight and normal arterial carbon dioxide levels (35 to 38 mm Hg). Protective ventilation involved end-expiratory pressures above the lower inflection point on the static pressure-volume curve, a tidal volume of less than 6 ml per kilogram, driving pressures of less than 20 cm of water above the PEEP value, permissive hypercapnia, and preferential use of pressure-limited ventilatory modes. After 28 days, 11 of 29 patients (38 percent) in the protective-ventilation group had died, as compared with 17 of 24 (71 percent) in the conventional-ventilation group (P<0.001). The rates of weaning from mechanical ventilation were 66 percent in the protective-ventilation group and 29 percent in the conventional-ventilation group (P=0.005): the rates of clinical barotrauma were 7 percent and 42 percent, respectively (P=0.02), despite the use of higher PEEP and mean airway pressures in the protective-ventilation group. The difference in survival to hospital discharge was not significant; 13 of 29 patients (45 percent) in the protective-ventilation group died in the hospital, as compared with 17 of 24 in the conventional-ventilation group (71 percent, P=0.37). As compared with conventional ventilation, the protective strategy was associated with improved survival at 28 days, a higher rate of weaning from mechanical ventilation, and a lower rate of barotrauma in patients with the acute respiratory distress syndrome. Protective ventilation was not associated with a higher rate of survival to hospital discharge.
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            Surviving Sepsis Campaign: International guidelines for management of severe sepsis and septic shock: 2008

            Objective To provide an update to the original Surviving Sepsis Campaign clinical management guidelines, “Surviving Sepsis Campaign guidelines for management of severe sepsis and septic shock,” published in 2004. Design Modified Delphi method with a consensus conference of 55 international experts, several subsequent meetings of subgroups and key individuals, teleconferences, and electronic-based discussion among subgroups and among the entire committee. This process was conducted independently of any industry funding. Methods We used the GRADE system to guide assessment of quality of evidence from high (A) to very low (D) and to determine the strength of recommendations. A strong recommendation [1] indicates that an intervention's desirable effects clearly outweigh its undesirable effects (risk, burden, cost), or clearly do not. Weak recommendations [2] indicate that the tradeoff between desirable and undesirable effects is less clear. The grade of strong or weak is considered of greater clinical importance than a difference in letter level of quality of evidence. In areas without complete agreement, a formal process of resolution was developed and applied. Recommendations are grouped into those directly targeting severe sepsis, recommendations targeting general care of the critically ill patient that are considered high priority in severe sepsis, and pediatric considerations. Results Key recommendations, listed by category, include: early goal-directed resuscitation of the septic patient during the first 6 hrs after recognition (1C); blood cultures prior to antibiotic therapy (1C); imaging studies performed promptly to confirm potential source of infection (1C); administration of broad-spectrum antibiotic therapy within 1 hr of diagnosis of septic shock (1B) and severe sepsis without septic shock (1D); reassessment of antibiotic therapy with microbiology and clinical data to narrow coverage, when appropriate (1C); a usual 7–10 days of antibiotic therapy guided by clinical response (1D); source control with attention to the balance of risks and benefits of the chosen method (1C); administration of either crystalloid or colloid fluid resuscitation (1B); fluid challenge to restore mean circulating filling pressure (1C); reduction in rate of fluid administration with rising filing pressures and no improvement in tissue perfusion (1D); vasopressor preference for norepinephrine or dopamine to maintain an initial target of mean arterial pressure ≥ 65 mm Hg (1C); dobutamine inotropic therapy when cardiac output remains low despite fluid resuscitation and combined inotropic/vasopressor therapy (1C); stress-dose steroid therapy given only in septic shock after blood pressure is identified to be poorly responsive to fluid and vasopressor therapy (2C); recombinant activated protein C in patients with severe sepsis and clinical assessment of high risk for death (2B except 2C for post-operative patients). In the absence of tissue hypoperfusion, coronary artery disease, or acute hemorrhage, target a hemoglobin of 7–9 g/dL (1B); a low tidal volume (1B) and limitation of inspiratory plateau pressure strategy (1C) for acute lung injury (ALI)/acute respiratory distress syndrome (ARDS); application of at least a minimal amount of positive end-expiratory pressure in acute lung injury (1C); head of bed elevation in mechanically ventilated patients unless contraindicated (1B); avoiding routine use of pulmonary artery catheters in ALI/ARDS (1A); to decrease days of mechanical ventilation and ICU length of stay, a conservative fluid strategy for patients with established ALI/ARDS who are not in shock (1C); protocols for weaning and sedation/analgesia (1B); using either intermittent bolus sedation or continuous infusion sedation with daily interruptions or lightening (1B); avoidance of neuromuscular blockers, if at all possible (1B); institution of glycemic control (1B) targeting a blood glucose < 150 mg/dL after initial stabilization ( 2C ); equivalency of continuous veno-veno hemofiltration or intermittent hemodialysis (2B); prophylaxis for deep vein thrombosis (1A); use of stress ulcer prophylaxis to prevent upper GI bleeding using H2 blockers (1A) or proton pump inhibitors (1B); and consideration of limitation of support where appropriate (1D). Recommendations specific to pediatric severe sepsis include: greater use of physical examination therapeutic end points (2C); dopamine as the first drug of choice for hypotension (2C); steroids only in children with suspected or proven adrenal insufficiency (2C); a recommendation against the use of recombinant activated protein C in children (1B). Conclusion There was strong agreement among a large cohort of international experts regarding many level 1 recommendations for the best current care of patients with severe sepsis. Evidenced-based recommendations regarding the acute management of sepsis and septic shock are the first step toward improved outcomes for this important group of critically ill patients.
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              Initiation of inappropriate antimicrobial therapy results in a fivefold reduction of survival in human septic shock.

              Our goal was to determine the impact of the initiation of inappropriate antimicrobial therapy on survival to hospital discharge of patients with septic shock. The appropriateness of initial antimicrobial therapy, the clinical infection site, and relevant pathogens were retrospectively determined for 5,715 patients with septic shock in three countries. Therapy with appropriate antimicrobial agents was initiated in 80.1% of cases. Overall, the survival rate was 43.7%. There were marked differences in the distribution of comorbidities, clinical infections, and pathogens in patients who received appropriate and inappropriate initial antimicrobial therapy (p < 0.0001 for each). The survival rates after appropriate and inappropriate initial therapy were 52.0% and 10.3%, respectively (odds ratio [OR], 9.45; 95% CI, 7.74 to 11.54; p < 0.0001). Similar differences in survival were seen in all major epidemiologic, clinical, and organism subgroups. The decrease in survival with inappropriate initial therapy ranged from 2.3-fold for pneumococcal infection to 17.6-fold with primary bacteremia. After adjustment for acute physiology and chronic health evaluation II score, comorbidities, hospital site, and other potential risk factors, the inappropriateness of initial antimicrobial therapy remained most highly associated with risk of death (OR, 8.99; 95% CI, 6.60 to 12.23). Inappropriate initial antimicrobial therapy for septic shock occurs in about 20% of patients and is associated with a fivefold reduction in survival. Efforts to increase the frequency of the appropriateness of initial antimicrobial therapy must be central to efforts to reduce the mortality of patients with septic shock.
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                Author and article information

                Contributors
                +43-662-448257780 , M.Duenser@salk.at
                Journal
                Intensive Care Med
                Intensive Care Medicine
                Springer-Verlag (Berlin/Heidelberg )
                0342-4642
                1432-1238
                14 February 2012
                14 February 2012
                April 2012
                : 38
                : 4
                : 557-574
                Affiliations
                [1 ]Department of Anesthesiology, Perioperative and General Critical Care Medicine, Salzburg General Hospital and Paracelsus Private Medical University, Müllner Hauptstrasse 48, 5020 Salzburg, Austria
                [2 ]Department of Critical Care Medicine, Mayo Clinic, Jacksonville, FL USA
                [3 ]Mahidol Oxford Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand
                [4 ]Department of Paediatrics and Emergency Medicine, BCCH and UBC Global Child Health, University of British Columbia and the Child and Family Research Institute, Vancouver, Canada
                [5 ]Department of Anesthesiology and Critical Care Medicine, Central State University Hospital, Ulaanbaatar, Mongolia
                [6 ]Department of Anaesthesia, Intensive Care Unit, Makerere University College of Health Sciences, Mulago Hospital, Kampala, Uganda
                [7 ]Department of Anaesthesia and Intensive Care, University College London Hospitals, London, UK
                [8 ]Department of Physiology and Pharmacology, Section for Anaesthesia and Intensive Care, Karolinska Institute, Karolinska University Hospital, Stockholm, Sweden
                [9 ]Department of Intensive Care Medicine, Laboratory of Experimental Intensive Care and Anesthesiology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands
                Article
                2468
                10.1007/s00134-012-2468-5
                3307996
                22349419
                8f07bddd-335a-4899-bc90-9ac4865b368b
                © Copyright jointly held by Springer and ESICM 2012
                History
                : 16 August 2011
                : 4 January 2012
                Categories
                Special Article
                Custom metadata
                © Copyright jointly held by Springer and ESICM 2012

                Emergency medicine & Trauma
                resource-limited settings,recommendations,management,middle-income countries,intensive care,low-income countries,sepsis

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