Clinical Considerations for the Treatment of Sepsis - Research Paper Example

Sepsis and septic shock are related blood infections that often lead to inflammation, organ damage, and death if left untreated. A description of international efforts to improve treatment of sepsis are described below; in addition to diagnostic considerations and treatment modalities. The successful resolution of sepsis requires not simply antibiotic/antibacterial therapy, but also a clinical awareness of inflammatory consequences, lapses in normal blood-pressure, and the urgency that comes from imminent organ damage through delay, or improper treatment. International campaigns to improve outcomes have emerged based upon the efforts of 11 different organizations in the guise of the Surviving Sepsis Campaign. An international effort to increase awareness and improve outcome in severe sepsis. On the agenda are data from hospitals around the world, where the condition has been tackled by decades of dedicated work from a variety of researchers. Sepsis and related disorders are potentially life-threatening syndromes that occur in association with a suspected infections whose signs and symptoms match at least two conditions of a systemic inflammatory response syndrome (SIRS). The major SIRS conditions are an increased heart rate, fever, and rapid respiration; the young and the elderly often exhibit early signs and symptoms of sepsis sometimes before exhibiting the full scope of SIRS criteria. The majority of sepsis cases are the result of bacterial infection. Those hospitalized with sepsis are treated with intravenous antibiotics, and therapy to alleviate organ dysfunction. (Davis & Stöppler, 2011) Sepsis and systemic inflammation that arises as a result are still responsible for as much as 70% of mortality in some intensive care units. (Reidemann et al. 2003) The mortality rate of severe sepsis includes organ dysfunction as a result of infection or subsequent failure in blood pressure and septic shock. This is in cases where hypotension does not respond to fluid resuscitation and correlates with organ dysfunction or blood pressure issues is too high by the standards of any medical practitioner. (Dellinger et al. 2004) Even before signs of organ failure, the odds of mortality can still reach up to 30%. Prevention of infections in the first place and the expedient diagnosis and treatment of sepsis are the best ways to prevent sepsis and moderate sepsis syndromes. The prognosis depends on severity of sepsis, and can change rapidly unless answered with swift, effective treatment. Also influential is the underlying health status of the patient; typically, the elderly have the worst prognosis.(Davis & Stöppler, 2011) Amongst medical practitioners, There is broad consensus that sepsis and the systemic inflammatory response syndrome (SIRS) is associated with a physiological failure to regulate the inflammatory response. The essential origin of this deficiency is still unknown. Ultimately, there are no quick-fixes to acute blood-borne, septic infection once symptoms have manifested. Other findings reveal complications that can arise with standard, supportive care. The aforementioned hypotension is often treated with IV fluid boluses to boost lower patient blood-pressure, but in cases of severe septic shock, this standard treatment has been shown to increase mortality in African children. (Davis & Stöppler, 2011) It is critical to evaluate both standard, and novel techniques to maximize clinical options. Attempts to pharmaceutically impede the specific response mediators of septic inflammation have experienced drawbacks. Though a new ray of hope has been found with the approval of (APC), activated protein C, for treatment of severe sepsis. In adults and neonates it has been shown to reduce mortality. (Kylat & Ohlsson 2006) There is evidence of a strong, clinical linkage between sepsis and inflammation; while bacterial toxins and penetration of tissue may have some adverse effects; often the most dramatic symptoms derive from our own bodys response to the invasion. Nonetheless, approaches that have employed purely anti-inflammatory treatments have not been successful in terms of patient outcome where sepsis occurs. (Hotchkiss and Karl, 2003) Specifically, doctors observe a hyperactivity of the inflammatory system during the initial onset of sepsis; at a time before significant concentrations of bacteria can be found in blood cultures through normal means. Systemic inflammatory response syndrome leads to sepsis in 50% of patients thusly affected. (Reidemann et al. 2003) Sepsis is among those acute disorders where time is most critical in terms of the right diagnosis and effective administration of treatment. Speed and appropriateness of therapy is often the deciding factor in the initial hours for determining the outcome. DIAGNOSIS To that end, thorough diagnosis - not just of the condition, but in terms of the identification of the organisms themselves, becomes a crucial link in the chain. Cultures should always be obtained and appropriately characterized before antimicrobial treatment. Davis lists the symptomatic criteria for a putative diagnosis: abnormal white blood cell count (>12000 cells/µL or 10% banded cells. body temperature either high (>100.4F or 38C) or low (20 breaths per minute or a reduced PaCO2 (partial pressure of carbon dioxide in arterial blood level) (tachycardia) >90 beats per minute at rest (Davis & Stöppler, 2011) The adult patient should exhibit a suspected source of a bacterial infection and possess at least two of the following criteria: an elevated heart rate (tachycardia), either a high (fever) or lowered temperature (hypothermia), rapid breathing (>20 breaths per minute or a reduced PaCO2 level), or an unusual white blood cell count beyond healthy ranges; either high, low, or composed of >10% band cells. In most instances, it is fairly easy to measure heart rate or fever or hypothermia with a thermometer, and to count breaths per minute without the aid of medical professionals. It is far more difficult to definitively prove the correct source of infection, but if the person has symptoms of infection including productive cough, or dysuria, or a fever, or a pus-presenting wound, The assumption becomes reasonable that a person with an infection may have sepsis. However, determination of the white blood cell count and PaCO2 must occur in a lab. In most cases, the definitive diagnosis of sepsis is made by the physician armed with data from laboratory tests. It is a virtual certainty with any case of sepsis, that the patients will require hospitalization. Treatment with effective, intravenous antibiotics, is standard, in addition to specialized therapy to alleviate any organ dysfunction; as Sepsis can rapidly result in potentially fatal organ damage and death. Alacrity is essential in therapy, delays will only allow the pathogens a greater chance of irreversible organ damage. Data suggests a 7% mortality increase per hour should antibiotics be delayed in cases of severe sepsis. (Davis & Stöppler, 2011) Treatment typically occurs in the intensive care unit (ICU) of the hospital. To optimize positive identification of causative microbial agents, at least two blood cultures should be acquired with one of them drawn percutaneously and the other drawn through each vascular access device. This may not hold true if the device was inserted within 48 hours. Other cultures from areas including urine, wounds, phlegm, cerebrospinal fluid, or other body fluids should be required before initiation of antibiotic therapy for a thorough diagnostic picture; based on the specific needs of the clinical situation in question. For blood cultures, typically Two or more blood cultures are optimal (Edelstein, 2011). One blood culture should be drawn through each lumen of all blood-vessel access devices. Obtaining blood cultures from standard phlebotomy and via a sample taken from a vascular access device is an indispensable comparative strategy for diagnosis, But Where the same organism is cultured from both samples, it is a virtual certainty that this organism is a causative agent in the case of sepsis. In any event, if a clear iatrogenic vector is located, it should be drained and sanitized to the extent possible. In a time when nosocomial infections are far too prevalent, there is the probability that the access device itself is a vector for infection. Culturing a sample taken from such a device two hours earlier then (if positive) reveals that the vascular access device itself is the source of the infection. As soon as bacterial growth is detected, diagnosis should begin promptly to identify the causative organism. In cases of severe infection; of course it is possible that the patients condition may prove too unstable for invasive procedures of transport from the ICU; medical professionals should be mindful of the benefits of portable ultrasound techniques; in cases where imaging is desirable. TREATMENT Initially, the patient suffering severe sepsis will require resuscitation due to sepsis-induced tissue hypoperfusion, which may include lactic acidosis. Resuscitation should begin at the onset of diagnosis not be delayed pending admission to the ICU. An elevated serum lactate concentration is a positive indication of tissue hypoperfusion in at-risk patients who would otherwise not have low blood pressure. The goal of treatment is to bring the following physiological variables within these ranges: Urine output #0.5 mL·kg-hr, Central venous pressure: 8–12 mm Hg Mean arterial pressure 65 mm HG, Superior vena cava oxygen saturation=#70%. (Dellinger et al. 2004) Once initial stability of the target physiological parameters has been reached, aggressive treatment must begin. While inflammation is associated with sepsis, treating inflammation alone is insufficient. (Hotchkiss & Karl, 2003). Other researchers have enjoyed preliminary success via the use of a recombinant antagonist for human interleukin-1, in terms of survival benefit for patients suffering gram-negative infections; a common culprit for sepsis. Among gram-negative bacilli likely to produce the syndrome are E. coli, E. corrodens P. S. aureus, P. aeruginosa, Haemophilus influenzae, Streptococcus species and Enterococcus species; however, there are a large number of bacterial genera that have been known to cause sepsis opportunistically. (David & Stöppler, 2011) There may be some clinical presentations that appear to be bacterial-induced sepsis, yet in fact are due to non-infectious causes; for these cases antimicrobials are inappropriate, and should be suspended to discourage the proliferation of drug resistant pathogens. To this end, it is beneficial to cultivate an awareness of the role of inflammation, for the broadest clinical awareness. But adding to the challenge, there can also be presentation of septic symptoms where the cultures initially appear negative. Clinicians must weigh these and other likely factors in a broad-contextual sense during the treatment phase. (Dellinger et al. 2004) But when those gram-negatives are detected, they must be engaged with antimicrobial/antibiotic therapies. The antibiotic intravenous administration should begin within one hour after the characterization of the causative organisms via cultures. But even in cases of strongly established, acute infection, the proper antimicrobials can still yield advantages in survival outcomes of ten percent over those that do not receive antibiotics. (Macarthur et al. 2004) Severe septic shock involving organ failure has exhibited a fatality range from 40-60% (Davis & Stöppler, 2011) Dellinger recommends pre-mixed antibiotics for use in emergency/critical care departments, although certain drugs may require more extensive preparation or infusion time than others. When drugs effective against the culprit organisms are identified; treatment must be calculated for adequate penetration into the effected tissues as well. Effective antibiotics to treat sepsis are combinations of two or three antibiotics given at the same time; (Dellinger et al. 2004), (David & Stöppler, 2011) many pre-mixture-combinations often include vancomycin to treat many MRSA infections. (methicilin-resistant staphylococcus aureus) Upon isolation of the infecting organism, laboratory analysis can determine which antibiotics are most potent in treatment of the pathogens, and thus prescribed. Use of antimicrobial drugs must be planned with specificity in order to reduce the probability that the patient will develop superinfection with inherently drug-resistant organisms; or with mutant resistant variants should the entire bacterial population not be eradicated. This must be balanced with the need to give a full-course of treatment sufficient to suppress the primary infection and likely opportunistic pathogens. Among resistant organisms, medical practitioners should be wary of vancomycin-resistance from Enterococcus species. (faecium), Candida-fungal species, and opportunistic, gram-positives saporophytes, such as Clostridium difficile. Initially, most physicians agree that a broad-spectrum antibiotic approach is valid in the early hours of acute sepsis. The strategy should be one of the aggressive elimination of all probable organisms; with every minute counting, and every hour in non-treatment measurably worsening survival odds. Most of us have been advised to avoid using antibiotics loosely, due to the possibility of encouraging the dominance of resistant strains, save in emergencies; but it is acute septic shock that constitutes just such an emergency. Yet here too, hypotension becomes an issue; with fluid volume and blood pressure too low; the ability of the appropriate antimicrobial agent to disseminate where needed in the body may be compromised. It is important that a team of doctors collaborate with a pharmacist to devise the most effective dosage tailored to the patients unique readings to ensure that the right treatment is delivered in sufficient amount in the right tissues. It is sound practice to reevaluate the antimicrobial strategy after a maximum of 72 hours for effectiveness based on bacteriological and clinical data, so that after the broad-spectrum first-wave has had a chance to work, a more narrowed tactic can be adopted. After 24-48 hours, it is probable that the lab will have viable cultures for taxonomic identification, and then a tailored regimen can be devised that is targeted to the offending species in particular. (Dellinger et al. 2004) Of course, there may be rare cases where a narrowed, specified antibiotic approach is not warranted; for patients suffering from neutropenia, (as in a deficiency of neutrophil/white blood cells) this deficiency in the immune system will not permit narrow-spectrum drugs to be effective; particularly bacteriostatic drugs; should the patients own defenses not be up to the task of repelling even invaders that are no longer replicating. For these patients, broad-spectrum antibiotics will likely be maintained throughout the duration of the septic condition. (Dellinger et al, 2004)​​ Concurrently, attempts are made to support the hypotension often exhibited during the treatment for sepsis. There are two standards means of fluid resuscitation, with inconclusive support for either the colloid or crystalloid method as being superior. But studies by Davis as mentioned above have demonstrated that fluid support efforts may yield questionable results and – in some cases worsen mortality odds. Vasopressor therapy may be indicated should fluid support methods fail to yield improvements in blood pressure. Below a certain point, the bodys autonomic ability to regulate pressure may be lost; as can often be the case where complications set in during acute sepsis. External, vasopressor support may prove essential to maintain adequate flow via minimal perfusion pressure. Blood lactate concentration may also serve as a useful benchmark for measuring progress of global blood perfusion. (Dellinger et al. 2004) In terms of pharmacological support besides antibiotics there is no irrefutable definitive evidence to recommend one catecholamine over the other, for the purpose of volemic maintenance. research suggests modest advantages of norepinephrine and dopamine over epinephrine, due to tachycardia risk, possibly dangers to splanchnic circulation; leading to decreases in stroke volume. Phenylephrine is the adrenergic agent with the lowest risk of inducing tachycardia; whereas Dopamine can raise mean arterial pressure and cardiac output, essentially due to an increase in stroke volume and heart rate. Either dopamine or Norepinephrine may be employed as the opening salvo to mediate hypotension during sepsis. Norepinephrine can increase mean arterial pressure due to vasoconstriction, with minimal change in heart rate and a smaller increase in stroke volume when compared with dopamine. Norepinephrine can be more potent than dopamine and thus more effective at eliminating hypotension during cases of acute septic shock. Dopamine may have inotropic benefits, but does carry a greater risk of cardiac valve regurgitation. (Kars et al. 2008) , (Schade et al. 2007), But this leads us into a comprehensive strategy with yet more options. With low heart output, and when efforts to boost perfusion pressure have been unsuccessful, dobutamine can be combined with vasopressor therapy as another arrow in the physicians quiver against the deadly consequences of sepsis. Dobutamine is a potent inotrope that has proven attractive due to the tendency of sepsis patient to experience erratic cardiac outputs. Their exact usage may depend upon whether the physician currently possesses the instrumentation to measure cardiac output in real-time. If not, dobutamine is often used in conjunction with norepinephrine and dopamine. With precise cardiac-monitoring; these drugs are often deployed separately to control specific levels of arterial pressure and heart output. (Dellinger et al. 2004) Steroids can be another option, for patients suffering septic shock despite fluid resuscitation; when vasopressor therapy is still required. This is due to findings that relative adrenal-gland insufficiency has been found in some cases to reverse septic shock. Adjustment of steroid levels and adrenal function then, can be used as a clinical tool to affect positive outcomes. SUMMARY Sepsis is a blood-borne infection, typically bacterial-induced with accompanying inflammation. The symptoms of sepsis are linked, but not entirely a product of the infection; Septic syndromes and like conditions are also a result of the bodies response to invasion, as much as a direct consequence of microbial activity. While supportive care can alleviate discomfort, the inflammation will not be fully treated until the bacterial infection can be successfully resolved. An application of this knowledge and other case studies tells us that treating only the inflammation, or the decreases in blood-pressure can be deleterious to the patient. Supportive care is needed to minimize damage from the symptoms while simultaneous, timely efforts are made to treat the underlying bacterial infection with effective antibiotic therapy. A treatment modality can then be devised in which symptoms are monitored; without their management constituting the entirety of the procedure. With bacterial infection being the root cause, one must marshal antibiotic use to eliminate infection as quickly as possible, while limiting opportunities for resistant strains to proliferate in a hospital setting without competition. CONCLUSION There is a plethora of evidence-based strategies documented herein and elsewhere published in the annals of medical literature. But comparative analysis of the impact of certain novel recommendations is not yet complete. In addition to the ongoing, vital research towards antibiotics; in terms of the arms-race between drug and bug, there is additional need for work towards comprehensive hypoperfusion remediation strategies. More studies could be done in this area to gain a more thorough picture of patient outcomes by comparison. Ways to build fluid volume safely and effectively could still be areas of needed, active research. In terms of the next phase of the aforementioned Surviving Sepsis Campaign is targeted to implement a core set of the available recommendations in hospital settings with the best chance of monitoring and comparing clinical impacts under safe, controlled conditions. "Change bundles" will be released in association with Healthcare reform organizations to achieve an ongoing collaborative process of improvement in healthcare. It is important to build motivational strategies to enhance compliance with the recommendations of joint agencies, as networks are built to better facilitate the monitoring of patient outcomes. REFERENCES Davis, Charles P. M.D. Stöppler, Melissa C. MD. 2011. What causes sepsis? Medicinenet.com ©1996-2011 MedicineNet, Inc. All rights reserved.  Dellinger, Phillip R. MD; Carlet, Jean M. MD; Masur, Henry MD; Herwig Gerlach, MD, PhD;Calandra, Thierry MD; Cohen, Jonathan MD; Gea-Banacloche, Juan MD, PhD; Keh, Didier MD; Marshall, John C. MD; Parker, Margaret M. MD; Ramsay, Graham MD; Zimmerman, Janice L. MD;Vincent, Jean-Louis MD, PhD; Levy, Mitchell M. MD; 2004 Surviving Sepsis Campaign guidelines for management of severe sepsis and sep.18092.E4 Copyright © 2004 by the Society of Critical Care Medicine DOI: 10.1097/01.CCM.0000117317.18092.E4 Edelstein, P. 2011. GUIDELINES FOR BLOOD CULTURE COLLECTION University of Pennsylvania Medical Center Guidelines for Antibiotic Use Penn Medicine, Philadelphia, PA. The Trustees of the University of Pennsylvania. http://health.upenn.edu/bugdrug/antibiotic_manual/table%20of%20contents.htm. Updated 2/24/2011. Accessed 10/9/2011 Hotchkiss, Richard S. M.D., Karl, Irene E. Ph.D. 2003 The Pathophysiology and Treatment of Sepsis. N Engl J Med 2003; 348:138-150 January 9. Kars, Marleen. Delgado, Victoria. Holman, Eduard R. Feelders, Richard A. Smit, Johannes W. A. Romijn, Johannes. Bax Jeroen J. and Pereira Alberto M. 2008. Aortic Valve Calcification and Mild Tricuspid Regurgitation But No Clinical Heart Disease after 8 Years of Dopamine Agonist Therapy for Prolactinoma. The Journal of Clinical Endocrinology & Metabolism September 1, 2008 vol. 93 no. 9 3348-3356 Kylat RI, Ohlsson A, 2006. Recombinant human activated protein C for severe sepsis in neonates. The Cochrane Library, Issue 2, 2006. http://www.thecochranelibrary.com Reidemann, Niels C. Guo, Ren-Feng. Ward, Peter A. 2003. Novel Strategies for the Treatment of Sepsis. 05/20/2003; Nat Med. 2003;9(5) © 2003 Nature Publishing Group. Schade, René M.D., Andersohn, Frank M.D., Suissa, Samy Ph.D., Haverkamp, Wilhelm M.D., Ph.D., and Garbe, Edeltraut M.D., Ph.D. 2007. Dopami ne Agonists and the Risk of Cardiac-Valve Regurgitation. N Engl J Med 2007; 356:29-38January 4, 2007 Read More