Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock: 2. We recommend that administration of IV antimicrobials be initiated as soon as possible after recognition and within 1 h for both sepsis and septic shock (strong recommendation, moderate quality of evidence; grade applies to both conditions). Rationale The rapidity of administration is central to the beneficial effect of appropriate antimicrobials. In the presence of sepsis or septic shock, each hour delay in administration of appropriate antimicrobials is associated with a measurable increase in mortality . Further, several studies show an adverse effect on secondary end points (e. LOS . Despite a meta- analysis of mostly poor- quality studies that failed to demonstrate a benefit of rapid antimicrobial therapy, the largest and highest- quality studies support giving appropriate antimicrobials as soon as possible in patients with sepsis with or without septic shock . The majority of studies within the meta- analysis were of low quality due to a number of deficiencies, including small study size, using an initial index time of an arbitrary time point such as emergency department arrival, and indexing of outcome to delay in time to the first antimicrobial (regardless of activity against the putative pathogen) . Other negative studies not included in this meta- analysis are compromised by equating bacteremia with sepsis (as currently defined to include organ failure) and septic shock . Many of these studies are also compromised by indexing delays to easily accessible but nonphysiologic variables such as time of initial blood culture draw (an event likely to be highly variable in timing occurrence). While available data suggest that the earliest possible administration of appropriate IV antimicrobials following recognition of sepsis or septic shock yields optimal outcomes, 1 h is recommended as a reasonable minimal target. The feasibility of achieving this target consistently, however, has not been adequately assessed. Practical considerations, for example, challenges with clinicians’ early identification of patients or operational complexities in the drug delivery chain, represent poorly studied variables that may affect achieving this goal. A number of patient and organizational factors appear to influence antimicrobial delays . These can include an unacceptably high frequency of failure to recognize the potential existence of sepsis or septic shock and of inappropriate empiric antimicrobial initiation (e. In addition, unrecognized or underappreciated administrative or logistic factors (often easily remedied) may be found. Possible solutions to delays in antimicrobial initiation include use of “stat” orders or including a minimal time element in antimicrobial orders, addressing delays in obtaining blood and site cultures pending antimicrobial administration, and sequencing antimicrobial delivery optimally or using simultaneous delivery of key antimicrobials, as well as improving supply chain deficiencies. Improving communication among medical, pharmacy, and nursing staff can also be highly beneficial. Most issues can be addressed by quality improvement initiatives, including defined order sets. If antimicrobial agents cannot be mixed and delivered promptly from the pharmacy, establishing a supply of premixed drugs for urgent situations is an appropriate strategy for ensuring prompt administration. Many antimicrobials will not remain stable if premixed in a solution. ![]()
This issue must be taken into consideration in institutions that rely on premixed solutions for rapid antimicrobial availability. In choosing the antimicrobial regimen, clinicians should be aware that some antimicrobial agents (notably . If vascular access is limited and many different agents must be infused, drugs that can be administered as a bolus or rapid infusion may offer an advantage for rapid achievement of therapeutic levels for the initial dose. While establishing vascular access and initiating aggressive fluid resuscitation are very important when managing patients with sepsis or septic shock, prompt IV infusion of antimicrobial agents is also a priority. This may require additional vascular access ports. Thrombosis has long been recognized as a potentially life-threatening complication in children with congenital heart disease (CHD), children with acquired heart. Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock: 2016. Intraosseous access, which can be quickly and reliably established (even in adults), can be used to rapidly administer the initial doses of any antimicrobial . In addition, intramuscular preparations are approved and available for several first- line . Several additional first- line . Studies have not been conducted to evaluate the pharmacokinetics of eculizumab in special patient populations identified by gender, race, age (pediatric or geriatric. Sickle Cell News for September. Landmark Article in New England Journal of Medicine. Health experts have long believed that sickle cell gene variants. Guidelines for the Management of Spontaneous Intracerebral Hemorrhage A Guideline for Healthcare Professionals From the American Heart Association/American Stroke. Case Records of the Massachusetts General Hospital. Case 22-2016 — A 65-Year-Old Man with Syncope, Dyspnea, and Leg Edema. Merck and the Merck Manuals. Merck & Co., Inc., Kenilworth, NJ, USA is a global healthcare leader working to help the world be well. From developing new therapies. Intramuscular absorption and distribution of some of these agents in severe illness has not been studied; intramuscular administration should be considered only if timely establishment of vascular access is not possible. We recommend empiric broad- spectrum therapy with one or more antimicrobials for patients presenting with sepsis or septic shock to cover all likely pathogens (including bacterial and potentially fungal or viral coverage) (strong recommendation, moderate quality of evidence). We recommend that empiric antimicrobial therapy be narrowed once pathogen identification and sensitivities are established and/or adequate clinical improvement is noted (BPS). Rationale The initiation of appropriate antimicrobial therapy (i. Failure to initiate appropriate empiric therapy in patients with sepsis and septic shock is associated with a substantial increase in morbidity and mortality . In addition, the probability of progression from gram- negative bacteremic infection to septic shock is increased . Accordingly, the initial selection of antimicrobial therapy must be broad enough to cover all likely pathogens. The choice of empiric antimicrobial therapy depends on complex issues related to the patient’s history, clinical status, and local epidemiologic factors. Key patient factors include the nature of the clinical syndrome/site of infection, concomitant underlying diseases, chronic organ failures, medications, indwelling devices, the presence of immunosuppression or other form of immunocompromise, recent known infection or colonization with specific pathogens, and the receipt of antimicrobials within the previous three months. In addition, the patient’s location at the time of infection acquisition (i. Potential drug intolerances and toxicity must also be considered. The most common pathogens that cause septic shock are gram- negative bacteria, gram- positive, and mixed bacterial microorganisms. Invasive candidiasis, toxic shock syndromes, and an array of uncommon pathogens should be considered in selected patients. Certain specific conditions put patients at risk for atypical or resistant pathogens. For example, neutropenic patients are at risk for an especially wide range of potential pathogens, including resistant gram- negative bacilli and Candida species. Patients with nosocomial acquisition of infection are prone to sepsis with methicillin- resistant Staphylococcus aureus (MRSA) and vancomycin- resistant Enterococci. Historically, critically ill patients with overwhelming infection have not been considered a unique subgroup comparable to neutropenic patients for purposes of selection of antimicrobial therapy. Nonetheless, critically ill patients with severe and septic shock are, like neutropenic patients, characterized by distinct differences from the typical infected patient that impact on the optimal antimicrobial management strategy. Primary among these differences are a predisposition to infection with resistant organisms and a marked increase in frequency of death and other adverse outcomes if there is a failure of rapid initiation of effective antimicrobial therapy. Selection of an optimal empiric antimicrobial regimen in sepsis and septic shock is one of the central determinants of outcome. Survival may decrease as much as fivefold for septic shock treated with an empiric regimen that fails to cover the offending pathogen . Because of the high mortality associated with inappropriate initial therapy, empiric regimens should err on the side of over- inclusiveness. However, the choice of empiric antimicrobial regimens in patients with sepsis and septic shock is complex and cannot be reduced to a simple table. Several factors must be assessed and used in determining the appropriate antimicrobial regimen at each medical center and for each patient. These include: (a)The anatomic site of infection with respect to the typical pathogen profile and to the properties of individual antimicrobials to penetrate that site.(b)Prevalent pathogens within the community, hospital, and even hospital ward.(c)The resistance patterns of those prevalent pathogens.(d)The presence of specific immune defects such as neutropenia, splenectomy, poorly controlled HIV infection and acquired or congenital defects of immunoglobulin, complement or leukocyte function or production.(e)Age and patient comorbidities including chronic illness (e. In addition, the clinician must assess risk factors for infection with multidrug- resistant pathogens including prolonged hospital/chronic facility stay, recent antimicrobial use, prior hospitalization, and prior colonization or infection with multidrug- resistant organisms. The occurrence of more severe illness (e. Given the range of variables that must be assessed, the recommendation of any specific regimen for sepsis and septic shock is not possible. The reader is directed to guidelines that provide potential regimens based on anatomic site of infection or specific immune defects . Since the vast majority of patients with severe sepsis and septic shock have one or more forms of immunocompromise, the initial empiric regimen should be broad enough to cover most pathogens isolated in healthcare- associated infections. Most often, a broad- spectrum carbapenem (e. However, several third- or higher- generation cephalosporins can also be used, especially as part of a multidrug regimen.
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