Pitfalls in the Treatment of Sepsis




Sepsis is a challenging, dynamic, pathophysiology requiring expertise in diagnosis and management. Controversy exists as to the most sensitive early indicators of sepsis and sepsis severity. Patients presenting to the emergency department often lack complete history or clinical data that would point to optimal management. Awareness of these potential knowledge gaps is important for the emergency provider managing the septic patient. Specific areas of management including the initiation and management of mechanical ventilation, the appropriate disposition of the patient, and consideration of transfer to higher levels of care are reviewed.


Key points








  • There have been recent changes in the diagnostic criteria for sepsis due to criticism of prior definitions.



  • The diagnosis of sepsis is challenging in special patient populations (eg, the elderly, children, patients taking medications that alter typical physiologic responses).



  • There is significant controversy in “bundled” care for septic patients because it is unclear which aspects are most helpful and which aspects may pose the potential for harm.



  • The disposition of a septic patient out of the emergency department may be one of the most consequential decisions the treating clinician can make. It should be approached considering not only the patient’s condition in the emergency department but also their likely trajectory following admission.



  • Strong consideration for transfer to a higher level of care should be made if it is not clear the resources required for the severity of illness can be met at their present institution.






Introduction


Emergency departments (ED) and emergency providers (EPs) have a vital role to play in the treatment and management of septic patients. Indeed, presentation and admission via the ED have been associated with more favorable outcomes. However, sepsis care in the ED has also been shown to have quality concerns, which include incorrect antimicrobial choice, delay to diagnosis, and failure to implement evidence-based treatments. In this article, the authors describe potential pitfalls in ED sepsis diagnosis and treatment and how to avoid or mitigate them. It should be noted that to avoid redundant content, this is not exhaustive.




Introduction


Emergency departments (ED) and emergency providers (EPs) have a vital role to play in the treatment and management of septic patients. Indeed, presentation and admission via the ED have been associated with more favorable outcomes. However, sepsis care in the ED has also been shown to have quality concerns, which include incorrect antimicrobial choice, delay to diagnosis, and failure to implement evidence-based treatments. In this article, the authors describe potential pitfalls in ED sepsis diagnosis and treatment and how to avoid or mitigate them. It should be noted that to avoid redundant content, this is not exhaustive.




Difficulty in diagnosis


Systemic Inflammatory Response Syndrome


The original definition of sepsis relied on the presence of 2 or more criteria outlined in the systemic inflammatory response syndrome (SIRS). In fact, the SIRS criteria acted as the building blocks for identifying and diagnosing sepsis, severe sepsis, and septic shock. SIRS incorporated changes in heart rate, body temperature, respiratory rate, and white blood cell count. If there was a known or suspected infection in a patient with 2 or more SIRS criteria, the patient was diagnosed with sepsis ( Box 1 ).



Box 1





  • Two or more of the following:



  • Temperature greater than 38°C or less than 36°C



  • Heart rate greater than 90 beats per minute



  • Respiratory rate greater than 20 breaths per minute or Pa co 2 less than 32 mm Hg



  • White blood cell count greater than 12,000/mm 3 or less than 4000/mm 3 or greater than 10% immature bands



Systemic inflammatory response syndrome

Data from Bone RC, Balk RA, Cerra FB, et al. Definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. The ACCP/SCCM Consensus Conference Committee. American College of Chest Physicians/Society of Critical Care Medicine. Chest 1992;101:1644–55.


It is known that systemic inflammation can occur in several different noninfectious conditions, decreasing the specificity of SIRS. Fig. 1 illustrates the presences of SIRS in some of the more common noninfectious conditions, including trauma and pancreatitis.




Fig. 1


Spectrum of infection, SIRS, sepsis, and severe sepsis.

( Data from Bone RC, Balk RA, Cerra FB, et al. Definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. The ACCP/SCCM Consensus Conference Committee. American College of Chest Physicians/Society of Critical Care Medicine. Chest 1992;101:1644–55.)


A diagnostic error may occur when the clinician prematurely excludes the diagnosis of sepsis in a patient where one of these other noninfectious systemic inflammatory states is present. This premature closure may result in delayed identification and treatment of a concurrent infection. The converse is also true; not all patients with systemic inflammation are infected and, in these patients, antibiotics are not indicated. In the ED, the undifferentiated nature of the patient and lack of initial clinical data compound these issues.


In addition, a recent study showed that SIRS criteria also lacked sensitivity for defining sepsis. Diseases like sepsis that are associated with significant morbidity and mortality demand a highly sensitive screening tool for diagnosis. Kaukonen and colleagues showed that 1 in 8 patients in the intensive care unit (ICU) with infection and organ dysfunction did not have 2 or more SIRS criteria. These SIRS-negative patients had a lower, but substantial, mortality associated with severe sepsis. Because of the shortcomings of the SIRS criteria as well as a better understanding of the pathophysiology of sepsis, the Sepsis 3.0 definition was developed.


Quick Sequential Organ Failure Assessment


It remains to be seen if the new sepsis definition will result in a more accurate and rapid diagnosis of sepsis. The authors of the new definition propose stepping away from using the SIRS criteria because they were considered to be unhelpful and confused both the adaptive and the maladaptive physiologic response to infection. They introduced the Quick Sequential Organ Failure Assessment (qSOFA) score to be used as a clinical score in patients outside the ICU with suspected infection that are more likely to have poor outcomes typical of sepsis. The qSOFA score consists of 3 variables: respiratory rate, altered mentation, and systolic blood pressure ( Box 2 ).



Box 2





  • Respiratory rate greater than or equal to 22 breaths per minute



  • Altered mentation



  • Systolic blood pressure less than 100 mm Hg



Quick sequential organ failure assessment

From Singer M, Deutschman CS, Seymour CW, et al. The third international consensus definitions for sepsis and septic shock (sepsis-3). JAMA 2016;315(8):805.


Concerns have been raised about the qSOFA score and its ability to provide useful guidance in patients with infection and suspected sepsis. It should also be noted that the qSOFA score was designed to predict worse outcomes in sepsis and not as a screening tool to be deployed in the ED.


Lack of a Gold-Standard Test


Another reason the diagnosis of sepsis can be difficult to make and may be missed is the lack of a reliable gold-standard test. The gold standard for identifying an infection is positive microbiological data, which is almost never available in the ED. EPs encountering a patient for the first time need to rely on other elements of the clinical picture in conjunction with the sepsis diagnostic criteria. There has been a great deal of investigative work into the role of various biomarkers aiding in the diagnosis of patients presenting with SIRS. Despite many publications, the role of a single biomarker has yet to be incorporated into daily clinical practice.


Special Populations and Effects of Medication


There are particular populations of patients that manifest subtle signs and symptoms of infection. This subtlety can lead to making the diagnosis of infection, and therefore sepsis, challenging. The elderly, the severely malnourished, and the immunosuppressed have abnormal responses to infection. It has been reported that fever will be absent in 20% to 30% of elderly patients with a known infection. They are more likely to present with nonspecific symptoms, such as altered mental status, fatigue, and anorexia.


The clinician often faces similar challenges with the immunosuppressed patient. Once again, typical responses to infection may be absent and mislead those caring for the patient. In addition, patients who are taking medications that blunt typical physiologic responses or alter clinical data due to their effect may have a delay to diagnosis. For example, β-blockade can limit tachycardia, whereas leukocytosis in a patient using steroids can be falsely attributed to the medication rather than an underlying infection.


Sepsis Is a Dynamic Process


Patients with an infection may decompensate while undergoing evaluation in the ED. For this reason, constant reassessment is necessary. The young college student with cough who had normal triage vital signs and initial suspicion of a simple upper respiratory infection may develop tachycardia, fever, and tachypnea, raising concern for pneumonia. The patient is now manifesting signs of sepsis and will likely need more care than initially thought. Sepsis is a dynamic process, and for this reason, patients require frequent reassessment by both nurses and EPs. Failure to do so may result in missing the diagnosis of sepsis.


Assuming a Bacterial Cause


Not all sepsis is caused by a bacterial infection. Failing to consider other causes of infection, such as fungal or viral causes, can result in a delay to diagnosis and ultimately a delay in appropriate treatment.


Fig. 2 , from Martin and colleagues, demonstrates that the incidence of sepsis is increasing, but also highlights an increase in the frequency of fungal causes of sepsis. The most common fungal infections in humans are species of Candida and Aspergillus. However, depending on the patient’s risk factors, other fungal infections may be present such as Cryptococcus, Pneumocystis jirovecii , or regionally prevalent organisms. The EP must review the history of the septic patient (eg, immunosuppression, travel, previous infectious causes), carefully consider if there is risk for either fungal or viral sepsis, and initiate the appropriate empiric treatment. Consultation with an infectious disease specialist may also be prudent in unclear or high risk cases ( Box 3 , Table 1 ).




Fig. 2


Number of sepsis cases by cause.

( Data from Martin GS, Mannino DM, Eaton S, et al. The epidemiology of sepsis in the United States from 1979 through 2000. N Engl J Med 2003;348(16):1546–54.)


Box 3





  • Immunosuppression (see Table 1 )



  • Exposure in endemic regions (Ohio and Mississippi River valleys, the desert Southwest)



  • Use of invasive indwelling vascular catheters (peripherally inserted central catheter, hemodialysis catheter, tunneled central lines)



  • Use of long-term urinary catheters or presence of nephrostomy/urostomy



  • Use of total parenteral nutrition



  • Widespread burns



  • Intestinal injury or conditions that weaken intestinal mucosal barriers



Risk factors for invasive fungal infection

Data from Refs.


Table 1

Examples of immunosuppression



















Pathogenesis Condition
Physiologic


  • Extremes of age



  • Pregnancy

Acquired


  • HIV/AIDS



  • Diabetes



  • Malnutrition



  • Malignancy/chemotherapy



  • Radiation treatment



  • Medications (steroids)

Congenital Inherited immunodeficiencies
Other


  • Cystic fibrosis



  • Systemic inflammation


Adapted from Leach R. The immune compromised patient. In: Leach R, Editor. Critical care at a glance. Hoboken: Wiley-Blackwell; 2014. p. 133–4.


End Organ Failure as the Initial Presentation of Sepsis


End organ failure may be the only presenting sign of sepsis. Although EPs are accustomed to searching for end organ failure if sepsis is already suspected, what happens if incidental end organ failure is noted in the absence of suspected sepsis? These patients could easily be overlooked in terms of a concurrent infection if the apparent new abnormality is viewed in isolation. In the ED, this presentation of sepsis is especially challenging because data supporting whether the changes are acute or chronic processes may not be accessible. In their publication defining the new definition of sepsis and septic shock, Singer and colleagues caution that even in the setting of a negative qSOFA screen, if there is suspicion for sepsis, further examination of end organ function should be performed. The EP should also view this in the opposite direction as well: if unexplained end organ failure is discovered, then underlying sepsis should be considered.


Sepsis can be a difficult diagnosis to make. Both failure to make the diagnosis and overdiagnosing sepsis can have significant consequences. When the diagnosis is missed, there is a delay in early interventions, including intravenous fluids (IVF) and antibiotics, which can lead to worse outcomes. Conversely, overdiagnosing sepsis can result in inappropriate antibiotic administration or IVF, resulting in complications such as the development of resistant organisms, Clostridium difficile colitis, or iatrogenic volume overload.




Pitfalls in the treatment of sepsis


Failure to Communicate to the Treatment Team


The management of sepsis is a team sport. The clinician may order fluids, antibiotics, and diagnostic studies, but unless the whole treatment team is aware of the concerns about the patient and their risk for decline, other patients or tasks may take priority. ED crowding, a proxy measure for how busy the clinical environment is, has been implicated as a factor causing delays to antibiotic treatment. Similarly, ED crowding has been associated with decreased sepsis resuscitation protocol compliance and contamination of bacterial blood cultures. Ensuring that each member of the treatment team has a shared mental model of how to manage the seriously ill patient is the responsibility of the treating EP as well as the department.


Invasive Mechanical Ventilation


Introducing the element of invasive mechanical ventilation adds complication to the treatment of sepsis and septic shock. Which patients that are septic or in septic shock require invasive mechanical ventilation? If mechanical ventilation is required, when is the ideal time to do it?


Type IV respiratory failure is found in patients who are in shock. These patients are placed on invasive mechanical ventilation during the resuscitation process with the goal of reducing the effort exerted by respiratory muscles, thereby lowering their oxygen consumption. Animal studies have shown that roughly 20% of cardiac output can be expended on the respiratory muscles. Invasive mechanical ventilation may benefit patients in septic shock by reducing respiratory muscle work and lowering total oxygen consumption, therefore increasing oxygen delivery to other vital organs, such as the heart, brain, and kidneys. The patient with septic shock may also have other types of respiratory failure, which can be supported by mechanical ventilation. These benefits need to be weighed against the potential adverse events that may occur during the process of intubation or while the patient remains intubated. Fig. 3 illustrates the risks and benefits of mechanical ventilation in septic shock.


Dec 13, 2017 | Posted by in Uncategorized | Comments Off on Pitfalls in the Treatment of Sepsis
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