Sepsis Systemic Immune Response Health And Social Care Essay

Sepsis is defined by the clinical signs and symptoms of a systemic immune response to infection. (1-2) Currently, sepsis on a worldwide level creates a significant level of mortality; and results in approximately one third of all Intensive Care admissions. (3-5) In Victoria alone there are approximately 8500 admissions to Emergency Departments with patients suffering from sepsis (3) and this number is increasing. Sepsis treatment can be initiated with a broad spectrum antibiotic, and then transferred onto a specific antibiotic regimen. Currently the level of pre hospital data available on the management of sepsis is very limited and the most advanced model has been initiated in the United Kingdom; including a pre hospital screening tool and then the hospital management known as the ‘Sepsis six’. (6) Pre hospital management can be utilised to the full potential of paramedics training and knowledge with the administration of pre hospital antibiotics; however this is not without risk. Perhaps the resistance to hand over the authority to paramedics in the United States is the notion of creating a super bug; similar to Methicillin-resistant Staphylococcus aures. This paper proposes that the administration of antibiotics in the pre hospital field does carry some risk, but the research suggest that the benefits clearly outweigh these risks. A new pre hospital guideline must be created due to the sheer number of Emergency Department admissions. The potential to make a significant difference to a patient’s outcome is imperative.

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Epidemiology

It has been highly researched and reported across the world that sepsis is a major cause of morbidity, mortality and places an enormous financial burden on the respective health system. (2, 5, 7) Statistics from Australia, United States and the United Kingdom are similar in nature and provide a wealth of information regarding the epidemiology of sepsis. Sepsis in the United States has been recognised as a public health issue, (8) with studies reporting that there are 300 reported cases per 100,000 with approximately 40% mortality. (5, 7-9) Severe sepsis in the United kingdom accounts for 27% of Intensive Care Unit admissions (4) and this is comparable with 23.8% of Intensive Care admissions in Victoria, Australia. (3) However it may be noted that this data is not very recent and that in the time of study the incidence was increasing by approximately 9% per year; whilst also reporting a decrease in the number of deaths associated with sepsis from approximately 45% to 37.7%. (5, 7, 9) Whilst many studies report the number of admissions, few report the age distribution of patients presenting with sepsis. Sundararajan et. al. highlight that the age distribution within their study was bimodal which identified that the age brackets at the extremes of the spectrum were over represented; with children less than 1 and adults in the 70-79 age bracket. (3) Upon further investigation into the types of causative pathology causing sepsis in these patients; gram positive organisms account for 28%, gram negative for 20%, fungal infections 2% and other organisms for 49%. (3) These figures are comparable with a study conducted by MacArthur et. al. of approximately 2634 patients with approximately 30% identified as gram positive and 26% gram negative bacteria. (10)

Pathophysiology and clinical features

What is Sepsis?

Sepsis is an infection induced syndrome and the clinical appearance in nature is the consequences of cellular interactions between the host and invading pathogen. (2, 11-12) Sepsis may be initialised by prolonged local inflammation to eliminate and clear the invading pathogen. The second line of defence against invading pathogens involves the production and activation of leukocytes at the local site of infection. (13-14) Throughout this phase, immune cells identify the pathogen through pattern recognition protein receptors on the cells. (15) An example of one of these receptors are toll like receptors and these are among the recognition receptors which have the ability to activate immune cells, inducing the production of pro-inflammatory cytokines and chemokines by the stimulation with bacteria and viral proteins (depending on the infection). (15-16) The invading pathogen may initiate the complement pathway of the immune system, allowing leukocytes to phagocytose [digest] the pathogen. If the host fails to limit the invading pathogen to a local area, the pathogen may invade the bloodstream. (16) If phagocytosis continues in the blood stream, toxic substances released by the pathogen may leak directly into the bloodstream; these include endotoxins released by gram negative bacteria (17) and lipoteichoic acid and peptidoglycan released by gram positive bacteria. (18) These by-products of phagocytosis and death of the cell may trigger a systemic activation of the complement system and stimulate the production of inflammatory cytokines. (19) Subsequently leading to an increased excessive and prolonged inflammatory response. (20) The result of this prolonged response leads to Systemic Inflammatory Response Syndrome (SIRS) which is the result of either direct or indirectly through the production and activation of nitrous oxide, oxidants and proteolytic enzymes which is known to have the potential to lead to inflammation induced organ injury. An example of this would be Acute Respiratory Distress Syndrome. (16, 20) SIRS is characterised by two or more of the following: body temperature >38°C or <36°C, heart rate >90 beats per minute, respiratory rate >20 per minute or arterial CO2 >32mmhg or a need for artificial ventilation, and white blood count greater than 12,000/mm3 or <4000mm3 or >10% immature forms. (21) SIRS can be also initiated not only by infection, it may also develop as a result of trauma, ischemic injury or sterile inflammation. (22)

What is severe sepsis?

If SIRS is left untreated, this response then cascades into what is known as severe sepsis. Severe sepsis is defined as ‘sepsis associated with organ dysfunction, hypoperfusion or hypotension responsive to fluid resuscitation’. (23) This can progress to septic shock, which involves ‘persistent hypotension unresponsive to fluid administration’. (23) An example of severe sepsis is called Multiple Organ Dysfunction Syndrome (MODS). This occurs when the infection of the bloodstream leads to progressive failure of two or more organ systems which result from a prolonged and uncontrolled inflammatory response. This organ dysfunction can lead to potential organ failure and death. (19)

Analyse evidence relating to the prehospital management of sepsis to identify risks and benefits of paramedic-initiated antibiotic therapy;

Sibley and Sibley (23) suggest that if Emergency Medical Services (EMS) or Paramedics have a patient suffering from suspected sepsis, that they must be managed with oxygen therapy, well documented vital signs and IV access to initiate fluid resuscitation. (24) The goal for EMS is to maintain systolic blood pressure just above 90mm Hg, with a Mean arterial pressure of 65mm Hg as any higher has the potential to worsen cardiac output, with adverse reactions. (24-26) Other studies support the notion of maintaining Mean arterial pressure at 65mm Hg as there is no clinical benefit to increasing this value higher. (27-28) Sibley and Sibley (23) contradict many other studies which suggest that early empiric antibiotic treatment of patients suspected of having sepsis is a standard practice; and the earlier treatment is initiated, the more positive the outcome. (2, 6, 8, 10, 16, 25, 29-30)

Empirical antibiotic treatment is the use of a broad spectrum antibiotic whilst therapeutic treatment with antibiotics is the initiation of antibiotic treatment after blood cultures are taken and the specific pathogen is identified. (31) Whilst empirical antibiotic treatment in the management of sepsis may be the initial drug of choice, it is in the patient’s best interest that appropriate antibiotic therapy is continued within the hospital. Appropriate antibiotic therapy is defined as “the use of an antimicrobial agent that is correct on the basis of all available clinical, pharmacological and microbiological evidence.” (32) With respect to the pre-hospital administration of antibiotic therapy, a recent study concluded that, if a patient is suffering septic shock, with each hour of delay in antibiotic administration after the onset of hypotension was associated with an average decrease in survival of approximately 8%. (33) However, a potential problem with empirical antibiotic treatment is that because sepsis is not the result of a single pathogen, the use of empirical antibiotics may not cover the pathogen causing the disease or illness.

Broad spectrum antibiotics may ‘bide time’ until blood cultures and appropriate testing can be done within a hospital setting. The current research suggests that the antibiotic selection used to treat conditions such as sepsis has a profound impact on patient outcomes (34) and this is also the case with inadequate antibiotic therapy, where the invading pathogen is not being effectively treated. (31) With regard to the empirical treatment, there are many different forms of pathogens that can cause sepsis, including Staphylococcus aures, Streptococcus pneumoniae, Escherichia coli, Klebsiella pneumoniae and Pseudomonas aeruginosa. (10) With this in mind, the aforementioned figures that roughly 28% of septic patients are caused by a gram stain positive, and 20% of patients are gram stain negative, and the rest being approximately 52% (3, 10), the notion is that broad spectrum antibiotics may not cover these specific pathogens, therefore rendering treatment useless. Potentially this could lead to a negative or adverse outcome.

An International Initiative, the ‘Surviving Sepsis Campaign’ (30, 35) and the Critical Care Community in the United Kingdom (6) initially concentrated on educating emergency department staff to promote the introduction of management of sepsis known as ‘Early Goal Directed Therapy’. Upon review, poor implementation of this initiative and resuscitation lead the education staff involved to a move to target the staff working in areas outside of the emergency department, including the implementation of an operationalised resuscitation management plan referred to as the ‘Sepsis Six’. The ‘Sepsis Six’ involves the administration of high flow oxygen, blood cultures, IV antibiotics, fluid resuscitation, measure serum lactate and haemoglobin and the insertion of a urinary catheter to measure urine output. The ‘Sepsis Six’ can be implemented by hospital staff with different skill sets in the first hour following the diagnosis of sepsis and can make a significant contribution to decreasing mortality. (6)

With respect to the rationale of the ‘Sepsis Six’ Robson et. al. proposes that components of this treatment can be initiated pre hospital, and interestingly, the authors also highlight that pre hospital sepsis care is unusual, but pre hospital cardiac care is common. The question remains as to why that is. Given that all the literature available suggests that there is a significant decrease in morbidity and mortality associated with early antibiotic treatment.

Within Ambulance Victoria, the current management for the treatment of severe sepsis has not been established. Only a guideline is specifically written for meningococcal septicaemia which allows paramedics to administer Ceftriaxone in the pre hospital field in the suspected case of meningococcal septicaemia. (36) Walker (37) proposes that in the year 2003, meningococcal disease affected approximately 500 Australians with approximately 100 of these cases presenting in Victoria. It would seem logical that an appropriate guideline is established for sepsis and severe sepsis based on the available data from Sundararajan et. al. (3) which suggest within a 4 year time frame, approximately 34,000 admissions to hospital were identified as suffering from sepsis. However, it must be recognised that this only accounts for 1.1% of the total number of admissions to Victorian emergency departments. (3) This is considerably more hospital admissions when compared with meningococcal septicaemia, with similar, if not more deadly consequences.

Perhaps the thought of utilising empirical antibiotic therapy causing a ‘super bug’ with sepsis is debateable. Whilst many studies report that Methicillin-resistant Staphylococcus aures is developed within the hospital system (38) rather than the community based setting; this attitude is changing with larger numbers of community acquired Methicillin-resistant Staphylococcus aures being reported, (39) with an estimated 50% of the population being a carrier of the bacteria. (40) The concern of doctors and other health professionals to the thought of initiating treatment with an empirical antibiotic may be a result of previous dealings with Methicillin-resistant Staphylococcus aures. Methicillin-resistant Staphylococcus aures has evolved and mutated to be come ‘resistant’ over generations with different strains of antibiotic that were initially effective at eliminating the bacterial pathogen. (41) The thought that exposing such a broad spectrum antibiotic; for example ceftriaxone, (a cephalosporin antibiotic) is that the exposure of a drug like this may potentially initiate a genetic mutation in potentially a wide spread of different strains of pathogens.

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Many studies have investigated the use of empirical antibiotics and also the possibility of not only one pathogen causing disease, therefore developing an appropriate antibiotic regime. This makes logical sense however, with consideration to the potential to cause a genetic mutation, exposing a pathogen to several antibiotics may have the potential to produce a resistant strain to not only one antibiotic, but several. The surprising news is that these studies have proven to have little or no extra effect in reducing mortality. (42-43)

Walker (37) proposes that the administration of pre hospital antibiotics by paramedics does have the potential for complications, including adverse reactions such as anaphylaxis and vasomotor collapse. However, the risk of antibiotic administration is no different to the administration of any other drug, with potential side effects and adverse reactions specific to individual patients.

Synthesise recommendations for paramedic management of sepsis based on available evidence.

Pre hospital data available on the treatment and management of septic patients are scarce. It is evident that more research needs to be undertaken in order to correctly identify septic patients and initiate early treatment. However the question remains as to whether data will ever be available due to the potential adverse reactions and the ethical dilemmas surrounding the prospective withholding of treatment to patients. The data that is available suggest that paramedics can make a difference in the potential outcomes of these patients. A mortality rate of close to 40% is unacceptable. It is proposed that paramedics undertake a similar model to the ‘Sepsis Six’ with an available pre hospital screening tool; similar to what the United Kingdom propose. This involves the identification of systemic involvement of the immune system by utilising the classification for SIRS; whilst using this in conjunction with history of a new infection. Taking both of these into consideration, persistent hypotension, low oxygen saturation and lack of urine output classifies pre hospital patients as suffering from severe sepsis. (6)

Paramedics are an integral part of the health care team and within the United States they are being overlooked and potential skills are being disregarded and this is still not understood when the literature suggest that early treatment does make a difference in outcomes. With regard to the early administration of antibiotics, not all patients will call at the onset of symptoms. Many will wait until the condition is unbearable or they feel like they are deteriorating, therefore it is important that empirical antibiotic therapy is undertaken at the earliest opportunity.

From the available literature; the United Kingdom’s model is the gold standard in terms of pre hospital screening and management of sepsis. Paramedics are highly trained health professionals and are able to manage septic patients accordingly, and as previously mentioned, the sepsis six involves high flow oxygen, blood cultures, IV antibiotics, fluid resuscitation, measured serum lactate and haemoglobin and urinary catheter and measure urine output. This paper does not propose that paramedics undertake all of the treatment outlined, but instead have the ability to initiate oxygen therapy, deliver intravenous fluid and antibiotics; and potentially have the ability to take blood cultures to hand over to the hospital. However, it must be emphasised that extra on scene time to complete these assessments and treatment must be taken into consideration as well as how long till the nearest hospital. Also important to note that paramedics must notify a receiving hospital so that the hospital can appropriately triage (44) and utilise the pre hospital taking of blood in the commencement of faster treatment and provide the ability to initiate an appropriate antibiotic regime.

Perhaps a review of the current guideline in Victoria is needed to extend the scope of paramedic practice to screen for potential septic patients, as the literature suggest that this current proportion of patients are exponentionally increasing. However; it may be easy to speculate changes that need to be made to the system, and this will take time and money. Walker (37) proposes from a management perspective there are significant costs associated with the antibiotics, training and assessment and ongoing replacement of antibiotics on all vehicles. Therefore it is imperative to continue research and therefore implement a new guideline into ambulance practice; which will benefit the health of all invested parties.

The early recognition and management of sepsis has implications on potential patient outcome. Sepsis has an extremely high mortality associated with it and as mentioned previously the sooner antibiotics can be administered; the rapid decrease in patient morbidity and mortality. With respect to the high numbers of presentations to Victorian emergency departments and intensive care admissions; this is mirrored throughout the world. One of the important points to understand that the admissions to intensive care can be avoided if sepsis is recognised earlier and paramedics may have a significant impact on the recognition and administration of antibiotics, as septic patients have the potential to be very unwell. The financial burden on the health system is enormous with one study speculating that the United States approximate spend on sepsis alone to be sixteen billion dollars. (2, 7) Data is unavailable from Victoria and Australia; however the costs associated with providing antibiotics for the management of sepsis will cost less than treating in an Intensive Care Unit.

Conclusion

One of the main recurring themes throughout this paper is that sepsis and severe sepsis have a high association with morbidity and mortality, even though the number of presentations have increased. The point needs to be emphasised that current management is not good enough. The research within hospitals is evident, that early antibiotic treatment of patients suffering from sepsis has profound effects on survival and recovery. Paramedics are potentially the first line of health care workers exposed to patients suffering severe sepsis and have the ability to act with broad spectrum antibiotics. Within Victoria, ambulances already carry Ceftriaxone; an example of a broad spectrum antibiotic. A guideline specific to sepsis needs to be developed and implemented in the pre hospital field, potentially on the basis of the United Kingdom’s model of recognising severe sepsis. The cost benefit analysis of implementing a new guideline, with the possible administration of antibiotics to more patients would severely outweigh the costs associated with an admission to an intensive care facility. The notion of taking pre hospital blood and notifying a receiving hospital of the potential septic patient may initiate appropriate treatment faster. Paramedics have the ability to make a difference with this time critical patient.