JB, a 23-year-old female, presented to the emergency department with fever, chills, nausea and abdominal pain. She was diagnosed with sepsis and treated initially with antibiotics and IV fluids. Her condition deteriorated after being transferred to a non-emergency ward, as key safety parameters like hypotension and elevated lactate were missed during handover. By Sunday, her symptoms met the criteria for septic shock, including low blood pressure, increased heart rate, and elevated lactate levels, indicating critical organ dysfunction from sepsis.

1. Deteriorating Patient with Sepsis: Early Diagnosis and Intervention
First published April 2017
Part of test scenarios for implementation of new sepsis guidelines
On Friday night, JB, a 23-year-old Caucasian female, presented at the emergency department with fever,
chills, malaise, nausea, increasing confusion, and mild diffuse abdominal pain. Sepsis was suspected
because of elevated temperature at 38.9˚C, elevated respiratory rate at 20 breaths per minute, and
signs of generalized infection. The study follows the patient's condition, her development, diagnostic
steps, and significant findings that led to the establishment of the diagnosis and decision which
interventions to use. Full description of the patient’s condition at transfer to a non-emergency ward is
described in Identification, Situation, Background, Assessment, and Recommendation forms (ISBAR)
chart that is included in Appendices. In 2016, the Surviving Sepsis Campaign (SSC) prepared new revised
International Guidelines for Management of Sepsis and Septic Shock (2016) (Surviving Sepsis Campaign).
The progression and management of sepsis and septic shock are explained utilizing the new 2016
Surviving Sepsis Guidelines as published by Rhodes et al. (2017).
Sepsis: definition, assessment, and management
The definition of sepsis and septic shock has changed multiple times in the last three decades to reflect
new research and clinical observations. As of 2016, sepsis is defined as a "life-threatening organ
dysfunction caused by a dysregulated host response to infection" (Kleinpell, Schorr & Balk, 2016). The
new diagnostic criteria for sepsis consist of an alteration of mental status, expressed as GCS score at 13
or below, a decrease in systolic blood pressure below 100 mm Hg, and respiration rate higher than 22
breaths per minute. A patient with two or more qSOFA criteria should be examined for organ failure
(Seymour et al., 2016). The qSOFA tool is not meant to replace previously developed tools but to be
used in addition to them. Systemic Inflammatory Response Syndrome (SIRS) significantly overlaps with
sepsis and systemic infection (Vincent, Martin, & Levy, 2016).
The initial clinical assessment was made using the Australasian Triage Scale (ATS) approach. The Primary
survey is aimed at the identification of life-threatening conditions, whilst the Secondary Survey includes
a full set of vitals, comfort measures, and head-to-toe assessment (Brown, 2013). JB, a 23-year-old
Caucasian female, presented at the emergency department on Friday night with fever, chills, malaise,
nausea, and mild diffuse abdominal pain. The initial examination revealed heart rate at 92 bpm, SpO2 at
100%, blood pressure 140/70 mm Hg, respiratory rate 20 breaths per minute, and temperature 39.9˚C,
steady regular symmetric pulse, petechial rash and adequate skin perfusion with CRT 1.5 sec. Her
consciousness was assessed as 14 at the Glasgow Coma Scale (GCS) due to confusion and lethargy. The
patient appeared breathless and somewhat incoherent when talking. The patient was hemodynamically
stable. The condition was consistent with a generalized infection, although it did not meet the qSOFA
standard for sepsis.
Early recognition of sepsis is essential for treatment success through screening. Core sets of
recommendations issued by the Surviving Sepsis Campaign include routine obtaining microbiologic
cultures, including blood, before starting antimicrobial therapy, providing doing so results in no
substantial delay in care. Isolation of the pathogen allows the de-escalation of antimicrobial therapy
(Rhodes, 2016).
Initial management of a patient with sepsis includes the stabilization of hemodynamic parameters by
the administration of crystalloids and a concerted effort to identify the offending agent. The treatment

2. of sepsis is organized into two recommendations called "bundles": the initial management that takes
place within six hours after the presentation for care, and the management bundle that takes place in
the intensive care unit (Dellinger et al., 2013).
The goals of the initial bundle are to lessen the immediate impact of uncontrolled infection and to assist
the cardiac and respiratory systems through the use of intravenous administration of fluids and
vasopressors and administration of oxygen therapy. Early diagnosis and aggressive resuscitation therapy
are of critical importance — delayed or inappropriate antibiotic treatment results in higher mortality
rates (Paul et al., 2010).
Once the samples for blood cultures and other parameters are collected, intravenous antibiotics shall be
administered to cover all possible sources of infection. The choice of antibiotics depends on the
suspected pathogen and its virulence and resistance patterns. The revised guideline recommends the
administration of initial antibiotic treatment within an hour of diagnosis of sepsis or septic shock after
the blood culture samples were taken. The combination of antibiotics shall then be adjusted according
to the laboratory findings ("Surviving Sepsis Campaign").
Empiric broad-spectrum antimicrobial therapy is recommended to cover all likely pathogens.
Antimicrobial therapy shall be revised and narrowed once the offending agent has been identified and
sensitivity established, or if adequate clinical improvement occurs. The revised guideline suggests
lowering of doses of antimicrobials and adjustment to the patient’s organ functions to ensure optimal
pharmacokinetic and pharmacodynamics profile and decrease side effects (Rhodes, 2016).
The most common bacteria isolated from patients with sepsis include Staphylococcus aureus (S.
aureus), Streptococcus pyogenes (S. pyogenes), Klebsiella spp., Escherichia coli (E. coli),
and Pseudomonas aeruginosa (P. aureginosa). Pathogens isolated from seriously ill patients display a
wide array of virulence factors such as endotoxins, lipopolysaccharides, exotoxins and enterotoxins.
Bacterial toxins modulate host cell defenses and allow the spread of infection throughout the body
(Ramachandran, 2013).
JB was started on crystalloids at 30 mL/kg, a combination of two broad-spectrum antibiotics, and low
flow oxygen closely monitored for any changes in hemodynamic parameters. Blood cultures, taken
before the first administration of antibiotics, revealed the presence of Gram-positive cocci, eventually
identified as Streptococcus pyogenes. The initial procedures were aimed at the localization of the source
of infection. Ultrasound of abdomen, pelvis, and chest X-rays did not show any abnormalities.
Cerebrospinal fluid was sterile. During the initial series of examinations, the patient became increasingly
confused and lethargic. Chronic skin infection previously diagnosed as acne and unspecified joint pain
were suspected as the most likely sources of the generalized infection. At this stage, the patient was still
hemodynamically stable. The full description of the patient’s condition is in the ISBAR chart, Appendix 1.
Handover: diagnostic tests and safe parameters
Intra-hospital transfers of critically ill patients lead to increased risk of adverse events. Incidents were
most likely related to equipment failure and physiological deterioration of the patient, including
hypotension and hypoxia. The number of incidents can be reduced through the implementation of
standardized protocols, procedures, and checklists relating to patient condition, personnel roles and
responsibilities, and organization and equipment and information exchange (Brunsveld-Reinders,
Arbous, Kuiper, & de Jonge, 2015). An example of such a checklist presented by Silva and Amante (2015)

3. includes a comprehensive review of the patient’s condition before, during, and after the intra-hospital
transport.
Due to multiple other medical emergencies that night, some of JB’s essential readings were not
performed and recorded. The nurse who was accepting the transfer of the patient to her noticed that
there were no new test results and no record of monitoring from the night before. The two most
critically important measures in this particular instance were slowly progressing hypotension, significant
because of a trend rather than absolute value, and hypoxemia expressed as blood lactate level.
Mean arterial pressure is the critical indicator for the initiation of vasopressor treatment. Patients with
mean arterial pressure (MAP) below 65 mm Hg shall be started on vasopressors such as norepinephrine
and titrated up to 35-90 μg/min (Dellinger, Schorr, & Levy, 2017).
The high level of lactate is defined as > 4 mmol/L. In shock states, the elevation of lactate is caused by
hypoperfusion and resulting tissue hypoxia. The functional cause of hypoperfusion is macro and
microcirculatory dysfunction and mitochondrial dysfunction. The patient presentation shows a
hypermetabolic state (Andersen et al., 2013). Blood lactate levels in septic patients are the indicator of
cellular metabolic failure and low tissue oxygenation rather than global hypoperfusion. Lactate is the
most important indicator in patients with sepsis because of its implications on treatment decisions. All
patients with elevated lactate > 4 mmol/L (36 mg/dL) shall be treated for septic shock regardless of
blood pressure (Dellinger, Schorr, & Levy, 2017).
The rationale for transfer to a non-emergency ward was that the patient no longer met the MET criteria
while on medication that could be administered elsewhere. Her normalizing body temperature at 37˚C
was misinterpreted as a sign of recovery from the infection. Her blood pressure was 90/60 mm Hg,
respiratory rate at 18, and she was˚ alert. Ominous trends that would suggest otherwise were not
available. Accurate and current clinical assessment is essential for a clinician to be able to make a
decision whether or not the patient can be transferred to non-emergency care. In JB’s case, the patient’s
dropping temperature was misinterpreted as improvement and a sign of a clearing infection rather than
a symptom of developing sepsis. However, it would be incorrect to blame a nurse at ICU for failure that
is of organizational nature. Comprehensive checklists and protocols relevant to patient transfer would
substantially improve patient safety.
Septic shock: pathophysiology and assessment
“Septic shock is a subset of sepsis in which circulatory, cellular, and metabolic alterations are associated
with a higher mortality rate than sepsis alone” (“Surviving Sepsis Campaign”). Septic shock is the result
of the maldistribution of blood flow. Hypo-perfusion of tissues leads to tissue hypoxia, metabolic
acidosis, the release of cytokines and oxygen free radicals, and cell death. The dysfunction of multiple
organ systems is quickly followed by multiple organ failure if the process is not halted. Systemic
Inflammatory Response Syndrome (SIRS) is characterized by elevated or lowered white blood cell count
or an increase in immature neutrophils (bands). Resulting progressive sepsis-related organ dysfunction is
called Multiple Organ Dysfunction Syndrome (MODS) (Kleinpell, Schorr & Balk, 2016).
Septic shock is the most critical stage of sepsis and results in the highest mortality rates. When the
infection is cleared, and tissue recovers, organ injury and secondary infections may occur. It is important
to understand that sepsis involves inflammatory, hemodynamic, tissue-perfusion, and organ dysfunction
variables, with the potential to advance to organ dysfunction. The complexity of sepsis and the possible
deterioration of septic shock are dependent on the virulence and load of the causative pathogen and
the present state of health and genetics of the host. Pro-inflammatory reactions that attack the

4. pathogen are responsible for parallel tissue damage. Anti-inflammatory responses limit tissue injury, but
also promote susceptibility to secondary infection (Angus, & van der Poll, 2013).
Septic shock develops in patients who remain hypotensive despite the administration of vasopressors
and whose serum lactate levels increase above 2 mmol/L despite adequate fluid resuscitation. Tissue
hypo-perfusion results in hypoxia, which triggers a cascade of biochemical processes within the cell due
to anaerobic metabolism and the resulting production of lactate. Release of cytokines, namely tumor
necrosis factor-alpha (TNF-α), interleukin-1 (IL-1), and other pro-inflammatory mediators, leads to
increased permeability of membranes and leakage of intravascular fluid into interstitial space. Some
bacterial toxins activate the same cascade. Activation of interleukins 6 and 8 (IL-6 and IL-8) leads to the
release of platelet-activating factor and formation of micro-thrombi within the vascular system. The
combination of these factors results in the impaired distribution of blood volume, vasodilatation, and
hypoperfusion — resulting in tissue hypoxia, which further exacerbates and worsens the problem.
Activation of the central nervous system and hypophyseal-adrenocortical axis leads to hypermetabolic
state, increasing tissue demand for oxygen. The effect of TNF-α and IL-1 on the myocardium is the cause
of depressed myocardial function, decreased ejection volume, and worsening hypotension.
Hypovolemia leads to centralization of blood circulation, limiting the flow of blood in the kidneys and
mesenterium, causing additional complications such as acute kidney injury (Brown, 2013).
Indicators of septic shock include persisting hypotension below 65 mm Hg despite vasopressors use, and
blood lactate > 2 mmoL/L despite adequate volume resuscitation (Seymour et al., 2016). Lactate is the
product of anaerobic metabolism, produced by most cells in the human body. Under anaerobic
conditions, it is the end-product of glucose metabolism. Under normal conditions, lactate is rapidly
cleared from the bloodstream by the liver. Elevated lactate is defined as 2 to 2.5 mmol/L by different
sources. The high level of lactate is defined as > 4 mmol/L. The term lactic acidosis shall be used if the
patient has high lactate and pH<7.35. In shock states, the elevation of lactate is caused by hypoperfusion
due to macro and microcirculatory dysfunction, mitochondrial dysfunction, and the presence of a
hypermetabolic state (Andersen et al., 2013). Blood lactate levels in septic patients are the indicator of
cellular metabolic failure and low tissue oxygenation rather than global hypoperfusion. Although lactate
does not provide a full picture of metabolic status as blood gases do, it is considered as the most
important indicator in patients with sepsis because of its implications on treatment decisions. All
patients with elevated lactate > 4 mmol/L (36 mg/dL) shall be treated for septic shock regardless of
blood pressure (Dellinger, Schorr, & Levy, 2017).
Accurate and rapid assessment is vital to halt the progression of the sepsis into septic shock. The patient
may or may not present with symptoms of bacteremia with or without complications such as acute
respiratory distress syndrome (ARDS), acute kidney injury (AKI), disseminated intravascular coagulation
(DIC), myocardial ischemia and dysfunction, mesenteric ischemia and other complications relating to
hypo-perfusion and organ dysfunction (Kalil and Bailey, 2016).
Invasive monitoring of patient conditions in septic shock is possible through the use of transpulmonary
thermodilution (Saugel et al., 2016). The technique is performed through the insertion of a central
venous catheter into the inferior or superior vena cava; a thermistor-tipped arterial catheter is usually
placed through the femoral artery into the abdominal aorta (Bendjelid, Giraud, Siegenthaler, & Michard,
2010). Cooled saline is introduced into the central venous circulation and passes through the right heart,
pulmonary circulation, and the left heart. Then the thermistor detects the thermal indicator bolus of
sale at the end of the arterial catheter, allowing the realization of a curve that shows how the cold
indicator is diluted through the patient’s cardiopulmonary circulation. Other hemodynamic values

5. available are CO assessment, cardiac preload, myocardial contractility, and the extravascular lung water
index (Kiefer et al., 2012; Tagami et al., 2010 and Casserly, Read, & Levy, 2011).
After transfer, JB’s GCS was still 13; her blood pressure dropped to 90/60 mm Hg heart rate increased to
141 bpm, and the temperature dropped to 37˚C and continued to drop. Her pulse was weak and narrow,
and respiratory rate > 22 breaths per minute. Peripheral capillary oxygen saturation (SpO2) dropped to
90%. Her skin turned very pale and showed signs of hypo-perfusion and edema. Laboratory findings
included leukocytosis, neutrophilia with a left shift, and hyperglycemia. JB’s qSOFA score increased from
one on the Friday night to three by Sunday mid-day when she developed tachypnea and systolic
hypotension in addition to the Glasgow Coma Scale score (GCS) of 13. JB’s condition indicated that she is
developing septic shock. She was hypotensive, and her mean arterial pressure (MAP) was dropping, and
her lactate level was 3.5 mmol/L. By Sunday night, JB was unable to void despite high fluid intake.
Oliguria increased creatinine and blood urea nitrogen, and electrolyte imbalance pointed to kidney
dysfunction. Moreover, JB started showing signs of dyspnea. Using the Berlin Definition, her ADRS was
200 mm Hg and PaO2/FIO2 ≤ 300 mm Hg, which qualifies as mild (Ranieri, Rubenfeld, Thompson, & et
al., 2012).
Septic shock: management
It is essential to ensure good perfusion and oxygenation of tissues. It is key to halt the deterioration of a
patient with sepsis into septic shock and prevent additional tissue injury. A patient with sepsis-induced
hypotension or lactate above 4 mmol/L shall receive a rapid infusion of crystalloids and low flow oxygen.
Patients with pneumonia or acute lung-injury may require high flow oxygen and intubation or
mechanical ventilation. When large volumes of crystalloids are required, supplementation of albumin
fluid should be considered to maintain intravascular volume. The septic shock is characterized by
hypotension that has not responded to previous efforts at fluid resuscitation. The first consideration is,
therefore, the use of vasopressors. The current vasopressor of choice is norepinephrine to maintain a
MAP of ≥65 mmHg, followed by vasopressin, epinephrine, and phenylephrine (Rhodes et al., 2016 and
Pittman, 2016)
Patients with mean arterial pressure (MAP) below 65 mm Hg shall be started on vasopressors such as
norepinephrine and titrated up to 35-90 μg/min. Once stabilized, norepinephrine can be continued
alone or in combination with vasopressin at 0.03 units/min, and the dose of norepinephrine can be
gradually decreased. If the patient continues to deteriorate, epinephrine and phenylephrine can be
added to achieve the MAP target (Dellinger, Schorr, & Levy, 2017).
Care must be taken to avoid excessive fluid resuscitation, as a negative fluid balance is preferred with
sepsis patients; particularly in patients with ARDS, negative fluid balance improves organ function
(Saugel et al., 2016).
The new guidelines suggest the use of dobutamine only patients with low risk of tachycardia and only in
low doses for renal protection. Attempts to increase cardiac output with dobutamine did not improve
outcomes. Dobutamine, and to a limited extent some other inotropes, may improve tissue perfusion
through increasing oxygen delivery (Rhodes et al., 2016).
Recommended interventions include prophylaxis of gastric ulcers and venous thromboembolism and
insulin for glucose control. Other interventions, such as sedation or dialysis, are reserved for special
situations. It is of critical importance to locate the source of infection. Corticosteroids, immunoglobulins,

6. blood purification, administration of blood products, bicarbonates, parenteral nutrition, and inotropes
are not recommended in patients with septic shock (Rhodes, 2017).
JB did not initially respond to norepinephrine but eventually stabilized when vasopressin and
epinephrine were added to the infusion. Oxygen was administered per nasal cannula. Antibiotic
treatment was adjusted to kidney function and to target Gram-positive cocci. Because of a large volume
of crystalloids and continuing extravasation, she received albumin to maintain intravascular volume. A
central venous catheter capable of hemodynamic measuring was inserted to enable peripheral access
and administration of intravenous fluids. To normalize her blood glucose levels, she received insulin.
Conclusion
Sepsis is a serious condition that still has a high mortality despite advanced care. The key to successful
treatment is early diagnosis and aggressive treatment. Recently revised treatment guideline offers an
excellent opportunity to review hospital practices in regards to the diagnosis and early aggressive
treatment of sepsis and septic shock. Screening for infections, including blood cultures, facilitates early
diagnosis and enables timely intervention. The case scenario presents a relatively low-risk patient
demographic presented with symptoms that could have been easily misdiagnosed. The clinical
symptoms corresponded with sepsis and rapidly progressed into septic shock. The patient benefited
from early diagnosis and aggressive intervention based on newly revised guidelines, and the fact that
these guidelines were implemented in clinical practice with fidelity. However, the patient later
deteriorated during a poorly controlled intra-hospital transfer that was signed off by a nurse who used a
standard that should not have been applied in this situation, consequently causing a delay in the
detection of deterioration and delayed care. Whilst the case shows evidence-based medicine at its best,
more can be done at the organizational level to facilitate communication during transfers, hospital
information management during handovers, including the design of checklists and application of
appropriate standards as well as roles and responsibilities for standard situations.
References
Andersen, L., Mackenhauer, J., Roberts, J., Berg, K., Cocchi, M., & Donnino, M. (2013). Etiology and
Therapeutic Approach to Elevated Lactate Levels. Mayo Clinic Proceedings, 88(10), 1127-
1140. http://dx.doi.org/10.1016/j.mayocp.2013.06.012
Angus, D., & van der Poll, T. (2013). Severe Sepsis and Septic Shock. New England Journal of
Medicine, 369(9), 840-851. http://dx.doi.org/10.1056/nejmra1208623
Bendjelid, K., Giraud, R., Siegenthaler, N., & Michard, F. (2010). Validation of a new transpulmonary
thermodilution system to assess global end-diastolic volume and extra- vascular lung water. Critical
Care, 14(6), R209. http://dx.doi.org/10.1186/cc9332
Brown, D. (2013). Lewis's Medical Surgical Nursing (1st ed., pp. 1706-1729). Elsevier Health Sciences
APAC.
Brunsveld-Reinders, A., Arbous, M., Kuiper, S., & de Jonge, E. (2015). A comprehensive method to
develop a checklist to increase safety of intra-hospital transport of critically ill patients. Critical
Care, 19(1). http://dx.doi.org/10.1186/s13054-015-0938-1
Casserly, B., Read, R., & Levy, M. (2011). Hemodynamic Monitoring in Sepsis. Critical Care Nursing Clinics
Of North America, 23(1), 149-169. http://dx.doi.org/10.1016/j.ccell.2010.12.009
Dellinger, R., Levy, M., Rhodes, A., Annane, D., Gerlach, H., & Opal, S. et al. (2013). Surviving sepsis
campaign: international guidelines for management of severe sepsis and septic shock: 2012. Crit Care
Med., 41(2), 580-637. http://dx.doi.org/10.1097/CCM.0b013e31827e83af.

7. Dellinger, R., Schorr, C., & Levy, M. (2017). A users’ guide to the 2016 Surviving Sepsis
Guidelines. Intensive Care Medicine, 43(3), 299-303. http://dx.doi.org/10.1007/s00134-017-4681-8
Kalil, Andre, and Kristina L Bailey. "Septic Shock". Medscape (2016): n. pag. Web. 10 Apr. 2017.
Kiefer, N., Hofer, C., Marx, G., Geisen, M., Giraud, R., & Siegenthaler, N. et al. (2012). Clinical validation
of a new thermodilution system for the assessment of cardiac output and volumetric
parameters. Critical Care, 16(3), R98. http://dx.doi.org/10.1186/cc11366
Kleinpell, R., Schorr, C., & Balk, R. (2016). The New Sepsis Definitions: Implications for Critical Care
Practitioners. American Journal Of Critical Care, 25(5), 457-464. http://dx.doi.org/10.4037/ajcc2016574
Paul, M., Shani, V., Muchtar, E., Kariv, G., Robenshtok, E., & Leibovici, L. (2010). Systematic Review and
Meta-Analysis of the Efficacy of Appropriate Empiric Antibiotic Therapy for Sepsis. Antimicrobial Agents
and Chemotherapy, 54(11), 4851-4863. http://dx.doi.org/10.1128/aac.00627-10
Pittman, R. (2016). Regulation of Tissue Oxygenation, Second Edition (1st ed.). San Rafael: Biota
Publishing.
Ramachandran, G. (2013). Gram-positive and gram-negative bacterial toxins in sepsis. Virulence, 5(1),
213-218. http://dx.doi.org/10.4161/viru.27024
Ranieri, V., Rubenfeld, G., Thompson, B., & et al. (2012). Acute respiratory distress syndrome: the Berlin
Definition. JAMA, 307, 2526-2533. http://dx.doi.org/10.1001/jama.2012.5669
Rhodes, A., Evans, L., Alhazzani, W., Levy, M., Antonelli, M., & Ferrer, R. et al. (2017). Surviving Sepsis
Campaign. Critical Care Medicine, 45(3), 486-552. http://dx.doi.org/10.1097/ccm.0000000000002255
Saugel, Bernd et al. "Advanced Hemodynamic Management In Patients With Septic Shock". BioMed
Research International 2016 (2016): 1-11. Web.
Silva, R., & Amante, L. (2015). Checklist for the intrahospital transport of patients admitted to the
Intensive Care Unit. Texto & Contexto - Enfermagem, 24(2), 539-547. http://dx.doi.org/10.1590/0104-
07072015001772014
Seymour, C., Liu, V., Iwashyna, T., Brunkhorst, F., Rea, T., & Scherag, A. et al. (2016). Assessment of
Clinical Criteria for Sepsis. JAMA, 315(8), 762. http://dx.doi.org/10.1001/jama.2016.0288
Surviving Sepsis Campaign. (2017). Survivingsepsis.org. Retrieved 8 April 2017, from
http://www.survivingsepsis.org/About-SSC/Pages/default.aspx
Tagami, T., Kushimoto, S., Yamamoto, Y., Atsumi, T., Tosa, R., & Matsuda, K. et al. (2010). Validation of
extravascular lung water measurement by single transpulmonary thermodilution: human autopsy
study. Critical Care, 14(5), R162. http://dx.doi.org/10.1186/cc9250
Vincent, J., Martin, G., & Levy, M. (2016). qSOFA does not replace SIRS in the definition of sepsis. Critical
Care, 20(1). http://dx.doi.org/10.1186/s13054-016-1389-z