1. Pediatric Septic Shock Collaborative
Educational Content (Sepsis, Septic Shock, & QI Primer)

2. Goals Review the impact of sepsis on patient outcomes
Define the sepsis disease spectrum
Review the evidenced based guidelines for the management of severe sepsis/septic shock
Outline quality improvement strategies for change
The goals of this talk will be to review the impact of sepsis on patient outcomes, to define the sepsis disease spectrum, to review the evidence based guidelines for the management of severe sepsis/septic shock, and finally to outline quality improvement strategies for change.

3. Impact of Sepsis on Patient Outcomes
Let’s begin with the impact of sepsis on patient outcomes.
Educational Content

4. Epidemiology Over 18 million cases worldwide each year
The annual incidence in the US of severe sepsis is approximately 3.0 cases per 1,000
Sepsis kills approximately 1,400 people worldwide EVERYDAY
According to the Surviving Sepsis Campaign, there are over 18 million cases of sepsis worldwide annually. In the US, the incidence of severe sepsis is approximately 3 cases per Finally, sepsis kills approximately 1400 people worldwide everyday!

5. Epidemiology-Pediatric
Sepsis is a leading cause of illness & death among U.S. children
> 42,000 cases annually (4th leading cause behind asthma, appendicitis, and poisonings)
5-10% overall mortality (0-5% healthy children; 10% if underlying medical conditions)
7-9 % of all childhood deaths are due to sepsis (more common than cancer)
Pediatric sepsis accounts for approximately 42,000 cases annually and is the leading cause of illness and death among children in the US, behind asthma, appendicitis, and poisonings. Overall mortality ranges from 5-10%, with increased mortality in children with underlying medical conditions. 7 to 9% of all childhood deaths are due to sepsis—it is more common than death from cancer.
Watson Am J Respir Crit Care Med :
Kutko Pediatr Crit Care Med 2003; 4:
Carcillo Crit Care Med (6):

6. Conditions Associated with High Hospital Resource Use
Mean Cost
Mean LOS
Severe Sepsis
~$40,600
31 days
IRDS
~$35,000
25 days
Spinal cord injury
~$25,000
16 days
Prematurity
~$24,000
22 days
Heart valve disease
~$23,000
9 days
In addition, sepsis represents the leading condition associated with high hospital resource use, in terms of costs and length of stay.
Watson RS et al, Am J Respir CCM 2003

7. Sepsis Disease Spectrum
Presentation of sepsis reflects a spectrum
SIRS
Sepsis
Severe Sepsis
Septic Shock
It is important to realize that the presentation of sepsis is a disease continuum—from SIRS to Sepsis, Severe Sepsis, and finally septic shock. Let’s review some definitions.

8. Definitions
Systemic Inflammatory Response Syndrome (SIRS): 2 of 4 criteria
Temp <36 or >38.5
HR >2 SD above normal for age (or bradycardia if <1 year old*)
RR > 2 SD above normal for age
Abnormal WBC or > 10% immature neutrophils
Sepsis: SIRS with suspected or confirmed infection
Severe sepsis: Sepsis + organ dysfunction or failure
SIRS, systemic inflammatory response syndrome, is a condition defined as meeting 2 of the following 4 criteria: temperature instability, tachycardia 2 standard deviations above normal for age, tachypnea 2 standard deviations above normal, and either abnormal white blood cell count or immature neutrophil count. Note the importance of hypothermia for any age and bradycardia for less than 1 year olds.
Sepsis is defined as SIRS in the face of suspected or confirmed infection, while severe sepsis is sepsis with organ dysfunction or failure.
Goldstein Pediatr Crit Care Med (1):2-8

9. Definitions
Septic shock= Hypothermia or hyperthermia and signs of cardiovascular organ dysfunction including
Altered or decreased mental status (inconsolable irritability, lack of interaction with parents and inability to be aroused)
Capillary refill ≥3sec (cold shock) or flash capillary refill (warm shock)
Diminished (cold shock) or bounding peripheral pulses (warm shock)
Mottled cool extremities (cold shock)
Decreased urine output <1 mL/kg/hr
Hypotension
Septic shock is defined as condition associated with hypothermia or hyperthermia, along with signs of cardiovascular organ dysfunction. Associated signs and symptoms include altered mental status, delayed capillary refill or flash refill, diminished or bounding peripheral pulses, mottled extremities, and decreased urine output.
Carcillo Crit Care Med (6):

10. 2 Major Types of Septic Shock
Warm Shock
Warm extremities
Flash capillary refill
Vasomotor Paralysis
High CI and low SVRI
Hyperdynamic heart with vasodilation
Cold Shock
Cold extremities
Capillary refill ≥ 3 sec
Myocardial Dysfunction
Low CI and high SVRI
Sick heart with significant vasoconstriction to maintain perfusion to organs
Septic shock can be further divided into cold shock, which is associated with low cardiac output and high systemic vascular resistance, and warm shock where there is high cardiac output and low systemic vascular resistance. Cold shock patients present with cold extremities and delayed cap refill while warm shock patients have warm extremities and flash capillary refill.

11. Definitions Compensated shock: Decompensated shock:
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Definitions
Compensated shock:
Systolic blood pressure within normal range with signs and symptoms of inadequate perfusion
Children more often present in compensated shock
Decompensated shock:
Signs of shock associated with systolic hypotension
Finally, shock can further be divided into compensated versus decompensated shock. In compensated shock systolic blood pressure is maintained with signs and symptoms of inadequate perfusion while in decompensated shock, patients have systolic hypotension.
Children are more likely to present in compensated shock.

12. Further Definitions Fluid-refractory shock: Dopamine-resistant shock:
Shock despite 60 cc/kg in 1st hour
Dopamine-resistant shock:
Shock despite adequate fluid resuscitation and 10 mcg/kg/min
Catecholamine-resistant shock:
Shock despite epinephrine or norepinephrine
Refractory shock:
Shock despite goal-directed use of inotropic agents, vasopressors, vasodilators, and maintenance of metabolic and hormonal homeostasis
(ANIMATION)
Just a few more definitions.
Fluid-refractory shock is shock despite 60 cc/kg in 1st hour of resuscitation.
Dopamine resistant shock is shock despite adequate fluid resuscitation and 10 mcg/kg/min
Catecholamine resistant shock is shock despite use of epinephrine or norepinephrine
And refractory shock is shock despite all interventions and goal directed therapy.
Carcillo Crit Care Med (6):

13. Sepsis: A Disease Continuum
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Sepsis: A Disease Continuum
Patients with life-threatening infection often present with fever and excessive, persistent tachycardia
Tachycardia, tachypnea, and signs of worsening perfusion precede hypotension
Hypotension is a late, ominous sign in pediatrics
Often followed by cardiopulmonary collapse
Stopping progression to hypotension (decompensated shock) via early aggressive interventions improves outcomes
(ANIMATION)
In summary, it’s important to remember that sepsis to septic shock is a continuum. Patients with life-threatening infections often present with fever and excessive, persistent tachycardia. This tachycardia along with tachypnea and worsening perfusion precede hypotension. Hypotension is a late, ominous sign in pediatrics that’s often followed by cardiopulmonary collapse. Evidence shows that stopping this progression to hypotension improves outcomes.

14. The Evidence
So what does the evidence show?
Educational Content

15. Each hour of delay associated with 50% increased odds of mortality
p < .001
Each hour of delay associated with 50% increased odds of mortality
In 2003, Han looked at pediatric transports to a tertiary pediatric center. They found that each hour of delay in following the guidelines was associated with a 50% increased odds of mortality.
Han et al., Pediatrics 112: 2003

16. Adult Mortality Reduced by 15% with Early Goal Directed Therapy
For every 6 adults with septic shock who are treated effectively, 1 death is prevented
In the adult population, Rivers, et al demonstrated that early, aggressive, goal-directed resuscitation reduced mortality by ~15%. For every 6 adults with septic shock who are treated effectively, 1 death is prevented
Rivers et al., NEJM 2001

17. Early Rapid Fluid Resuscitation in Pediatric Septic Shock is Associated with Improved Outcomes
Fluid-sensitive
% Mortality
Time-sensitive
(ANIMATION)
In addition, the guidelines call for early and aggressive fluid resuscitation. It has been shown that mortality is both fluid-sensitive, where mortality increases with decreased amount of fluids given.
And is time sensitive, where mortality increases with delays to fluid administration.
Oliveira et al, Ped Emergency Care 24:2008

18. Every hour delay in receiving effective antibiotics is associated with a 7.6% decrease in survival in adults with septic shock
In adults, it has been shown that each hour of delay to receiving effective antibiotics was associated with an almost 8% decrease in survival.
Kumar et al, Crit Care Med 34: 2006

19. Evidenced Based Guidelines
Let’s now review the actual guidelines.
Educational Content

20. Pediatric Septic Shock Guidelines
Early aggressive fluid resuscitation (up to 60 cc/kg in the first 15 minutes)
Proportionally larger quantities of fluid in children
Initial volume resuscitation commonly requires cc/kg but can be as much as 200 cc/kg in the 1st hour
Reassess between boluses for signs of volume overload—hepatomegaly, rales, gallops
Vasoactive agents for fluid refractory shock
Can be given through peripheral IV until central access is obtained
Initiate dopamine for fluid-refractory shock
Initiate norepinephrine (warm shock) or epinephrine (cold shock) for fluid-dopamine-refractory shock
Remember short half life therefore rapid titrations are needed
Hydrocortisone for adrenal insufficiency
Identify need for invasive cardiovascular monitoring for fluid-refractory shock
(ANIMATION)
The American College of Critical Care Medicine in 2002 introduced practice guidelines for the treatment of septic shock. It was revised in 2007 and published in They are internationally recognized, translated into multiple languages and incorporated in the Pediatric Advanced Life Support algorithm.
First, the guidelines call for early aggressive fluid resuscitation, up to 60 cc/kg in the 15 min minutes. Compared to adults, children require proportionally larger quantities of fluid. It is not uncommon that for children to require more than 60 cc/kg, sometimes up to , even 200 cc/kg. It is important to reassess children between each bolus to monitor for signs of volume overload—hepatomegaly, rales, gallop.
Second, if shock persists despite fluids, vasoactive agents should be utilized. Agents can be started through a peripheral iv until central access is established. In general, dopamine is recommended for fluid-refractory shock. For dopamine resistant shock, norephinephrine is recommended for warm shock and epinephrine is recommended for cold shock. As these pressors have a short half life, rapid titrations are needed to gain effect.
For patients with adrenal insufficiency, stress dose hydrocortisone should be given.
Finally, in children identified as having fluid refractory shock, invasive cardiovascular monitoring may be needed.
Care should coordinated early with critical care services on timing and location (ED vs ICU) of invasive monitoring to help facilitate goal directed therapy.
Carcillo Crit Care Med (6):

21. Pediatric Septic Shock Guideline
Therapeutic goals include:
Capillary refill time ≤ 2 seconds
Normal pulses with no differential between peripheral and central pulses
Warm extremities
Urine output > 1 cc/kg/hr
Normal mental status
Normal blood pressure for age
Therapies should be aimed at improving perfusion to the body. Specific goals include return of normal mentation, blood pressures, capillary return, and pulses. One important goal should be presence/improvement of urine output.

22. ACCM Guidelines: 60 cc/kg in 15 minutes PALS Guidelines:
The ACCM guidelines have been incorporated into the PALS algorithm. However, one major difference exists between the two. While ACCM guidelines call for 60 cc/kg within 15 minutes, PALS recommends 60 cc/kg within 60 minutes. 22

23. The PSSC Clinical Pathway
Let’s walk through a modified algorithm based on PALS algorithm.

24. 0-20 min
(ANIMATION)
Within the 1st 20 minutes, the algorithm calls for recognizing signs of poor perfusion.

25. TRIAGE TRIGGER TOOL High Risk Conditions Vital Signs
At risk identification tools can be started from triage and utilized throughout the ED stay. Above is an example utilizing vital signs, signs of perfusion, and consideration for the presence of high risk conditions.
Signs of Perfusion

26. TRIAGE TRIGGER TOOL Identify as at risk for sepsis if: Hypotension or
Meets 3/8 criteria or
Meets 2/8 criteria if high-risk
At risk identification tools can be started from triage and utilized throughout the ED stay. Above is an example utilizing vital signs, signs of perfusion, and consideration for the presence of high risk conditions.

27. 0-20 min
(ANIMATION)
In children identified as having signs of poor perfusion, access should be quickly obtained via a peripheral IV or IO and oxygen should be placed on child. It should be noted that PALS recommends establishing an IO if unsuccessful IV attempt within 90 seconds. Appropriate laboratory and radiographic evaluation should be conducted to identify the possible source of infection. Finally, rapid administration of fluids should be started in 20 ml/kg aliquots via push-pull system, a pressure bag, or through a rapid infuser. Antibiotics should also be ordered with goal of delivery within 60 minutes.

28. 20-60 min
(ANIMATION)
If there is no clinical improvement, subsequent boluses in 20 ml/kg aliquots, up to and over 60 ml/kg should be given until perfusion improves or signs of fluid overload develop- rales or hepatomegaly. Metabolic abnormalities such as hypoglycemia and hypocalcemia should be corrected.

29. >60 min
(ANIMATION)
For fluid refractory shock, dopamine or epinephrine is recommended for cold shock and norepinephrine for warm shock. These pressors can be started through a peripheral iv until central access is gained. Transfer to intensive care unit should be considered.
For catecholamine resistant shock, begin hydrocortisone if at risk for adrenal insufficiency.

30. Intubation and Septic Shock
Low threshold for ET intubation even without primary respiratory failure
Up to 40% of cardiac output may be devoted to work of breathing; this can be unloaded
Atropine, ketamine preferred agents for sedation
Caution with etomidate
For patients with septic shock, there should be a low threshold for endotracheal intubation even without primary respiratory failure. Up to 40% of cardiac output may be devoted to work of breathing. Atropine and ketamine are the preferred agents for intubation. Etomidate should be used with caution due to concerns for adrenal suppression.

31. Pediatric Septic Shock Collaborative
Educational Content (Quality Improvement Primer)

32. QI BASICS Create a mission statement Identify specific aims
Identify measures
Gather key stakeholders
Needs assessment
Rapid cycle change
The following slides will introduce the use of standard QI tools to identify the problem, implement improvement strategies and determine what your institution will use to measure and track progress. An example of an institutional sepsis intervention will be used to demonstrate use of these tools.
We will focus on creating a mission statement, identifying specific aims, creating effective measures, gathering a team of stakeholders, performing a needs assessment and engaging in rapid cycle change.

33. Plan-Do-Study-Act
In the model of improvement, one must identify the aims by determining what it is you would like to accomplish, identify measures to know what changes represent an improvement and identify further changes that need to be made to result in continued improvement
These three questions are incorporated in the Plan Do Study Act Cycle which tests the changes you have made in a systematic way. As we go through an example of how to use QI tools for a sepsis improvement project, note which component of the PDSA cycle is being used as illustrated by the PDSA symbol in the corner of each slide.

34. Example of qi initiative
The following slides follow the quality improvement effort at improving care of septic shock at one hospital.
Quality Improvement Primer

35. Mission Statement
To improve the care of children with severe sepsis and septic shock in a pediatric emergency medicine department
The mission statement allows everyone as part of the project to be on the same page. It is broader than the aim statement to follow. People often fall back on to the mission statement when during the quality improvement intervention the granular details detract from the overall goal of the project and re-focusing is needed.

36. Background
PALS (2006)
Recognize altered mental status and poor perfusion
Establish vascular access and begin resuscitation
5 min
5 min
1st hour
1st hour: Push repeated 20 mL/kg IVF up to 3
Administer antibiotics STAT
60 min
60 min
As in the aforementioned slides guidelines exist for ideal septic shock care.
((Firstly, one must identify the relevant literature to determine which components the group should focus on. Here this institution used the PALS 2006 guidelines.
Adherence to the 5 time points within the algorithm was evaluated: time to recognition (click for animation), time to vascular access (click for animation), time to delivery of 60ml/kg within 60 minutes (click for animation) , time to delivery of antibiotics (click for animation) and time to initiation of a vasoactive drug (click for animation) .
Fluid responsive (i.e. normalization of BP and/or perfusion)? no
yes
Consider ICU monitoring
Begin vasoactive drug therapy and titrate to correct hypotension / poor perfusion
60 min
Modified from Pediatric Advanced Life Support Manual. American Heart Association

37. Needs Assessment
A needs assessment was then performed. This is done by attempting to generate data for the problem. This allows for objective reasons to undertake change. Here institutional adherence to the 5 components of the PALS guidelines was examined.
One can see that for the recognition, vascular access and antibiotic intervention we adhered to the goal in the majority of cases and the median time to the intervention was below goal. Fluid and vasoactive drug delivery however were more problematic and thus where future interventions would focus upon.

38. Total algorithm adherence Total algorithm non-adherence
Needs Assessment
Fluid
adherence
n= 29
(mean # days)
non-adherence
n= 98
% decrease
P value
Hospital
LOS
8.0
11.2
57%
0.039
ICU LOS
5.5
7.2
42%
0.024
Total algorithm adherence
n= 15
(mean # days)
Total algorithm non-adherence
n= 112
% decrease
P value
Hospital
LOS
6.8
10.9
57%
0.009
ICU LOS
5.5
59%
0.035
As part of the needs assessment one should use specific institutional outcome data if available. For example here poor outcomes were identified from under-resuscitation. Hospital and ICU length of stay increased with poor fluid and (click for animation) total algorithm adherence. This data highlights the importance and relevance for the primary stakeholders.

39. Aim Statement
Increase adherence to the Pediatric Advanced Life Support Guidelines
for severe sepsis and septic shock in the Children’s Hospital Boston Emergency department
from 19% overall adherence to the 5 component bundle to > 90% adherence
within one year
An Aim statement should follow, which attempts to narrow down the mission statement by asking
What? Where? By how much? And By when?
Your goal should be a stretch number as you are aiming for near perfection.
In this example, this institution wished to READ SLIDE

40. Secondary Aims COMPONENTS OF THE BUNDLE:
Improve recognition: > 90 % of patients are recognized within 5 minutes of meeting definition of SS
Improve attainment of vascular access: (peripheral, intraosseous or central): >90% of patients have access within 5 minutes of meeting definition of SS
Improve delivery of fluid: > 90% of patients have 60 ml/kg of isotonic fluid delivered within 60 minutes of meeting definition of SS
Improve delivery of antibiotics: >90% of patients have antibiotics delivered within 60 minutes of meeting definition of SS
Improve delivery of vasoactive agents: > 90% of patients have a vasoactive agent begun at 60 minutes of meeting definition of SS
You can further breakdown the AIM statement into secondary aims which are more granular. These secondary aims are often what process measures will be followed, that is the small components that need to be improved in order to achieve improvement in the larger aim and outcome measures.
Here goals were identified for the 5 components of the algorithm: recognition, vascular access, fluid delivery, antibiotics and vasoactive agents.

41. Measures Outcome Measures Mortality Length of stay in ICU, hospital
Days on vasoactive agents
Multiorgan dysfunction syndrome
Process Measures
Adherence to recognition, vascular access, IV fluid, antibiotic and vasoactive agents
Balancing Measures
ED length of stay
Increased respiratory support due to pulmonary edema
3 types of measures should be followed as the intervention is carried forth. Outcome measures (click for animation) are the final measures that are clinically important such as mortality and days on vasoactive agents. Process measures (click for animation) are the smaller goals that need to be met such as adherence to the 5 components of the bundle. With improvements in one’s process measures, outcomes should ideally improve. Balancing measures (click for animation) finally ensure that no other clinical processes are suffering from the intervention such as no increased ED length of stay or increases in pulmonary edema cases from aggressive fluid resuscitaiton.

42. Upper Level Management
Team Members
Middle Management
Frontline workers
Physicians
Nursing
Respiratory
Nursing assistants
Pharmacists
Research Assistants
Upper Level Management
Physician Leadership
Nursing Leadership
Hospital Leadership
Pharmacy Head
Identify the relevant team members who should represent all the major stakeholders. They should be present for the initial meetings strategizing improvement and all PDSA cycles where changes are implemented as the process continues. Here there was identification of frontline workers, including those that had direct patient contact, those from middle management and those from upper level management. This latter component is crucial for implementation, as this group can remove administrative obstacles and provide necessary organizational and financial support as needed.
Statistical Support
Computer Support

43. Equipment People Methods Environment 60ml/kg within 60 minutes
Holding for other procedures
MD’s are too busy with patient to put in orders
CA’s cannot be reached
Need labels to sent labs
CA’s usually get labels but are busy holding for IV
CA phones numbers not uniformly posted, some don’t have phones
Can’t find pressure bag
Hesitance to use IO
Waiting for IV team
Don’t know how to use pressure bag
People don’t know pharmacy number
No IV access
Wrong
fluid device
used
Access tenuous
Pharmacists difficult to get a hold of
Don’t know to use pressure bag
60ml/kg within 60 minutes
No pocket cards for bedside reference
Too many patients
Not enough MDS
Poor knowledge of protocol
MD’s don’t know who the nurses are
Too busy to recognize septic patients
No educational sessions
No visible algorithms
The team, once identified should use the QI tools available to identify the primary barriers to care.
Here is an example of use of an Ishikawa fishbone diagram used as part of the needs assesment. The goal is identified on the right. The barriers are compartmentalized into subgroups. First and second order barriers are then identified to really determine the specific possibilities for why a process is underperforming.
For example in this institution it was identified that there was poor knowledge of septic shock protocols (click for animation) . This was postulated to be due to lack of available references (click for animation), lack of educational support (click for animation) and no personal accountability of feedback (click for animation) .
No accountability/feedback
Poor RN/MD communication
No trigger system
Many trainees to educate, many adult trainees
Many trainees
Methods
Environment

44. Needs Assessment: Pareto
The pareto diagram is based upon the pareto principle that 80% of the problem is caused by 20% of the issues. There are specific methods to generate this chart.
Here it was identified that non-adherence to inotropes, fluid delivery and poor vascular access were contributing to 80%of the problem. This allows one to focus their interventions to key problems that will generate the most change.

45. Change Hypotheses Educational sessions MDs Educational sessions RNs
Didactics
Net learning
Skills Day (pressure bags)
Computer Orderset
Visible algorithm
Posters
Pocket cards
Clock
Bedside Survey
October 6
September 21, October 2
Ongoing
October 12
September 26
October 16
Determine your change hypotheses. This refers to the possible changes you will make as you work through the PDSA cycles. These changes should be based upon the institutional barriers that have been identified.
October 27
October 19
October 10

46. One of the change hypothesis was providing a posted bedside algorithm that was clear and concise.

47. Another change was distribution of pocket cards with expansion of the details of the algorithm to all physicians and nurses

48. Utilize unique “gimmicks” that people will remember and associate with the protocol. Here this institution utilized a countdown clock once a patient was identified to ensure that all providers carried out the time-sensitive interventions in the time recommended.

49. ED Septic Shock Orderset
Use of electronic ordersets were also a change hypothesis that automated the process. If available, the electronic medical system should be utilized to standardize care.

50. Personal Feedback
Hi,
This is to let you know that your patient  AT (24 year old Asperger's, panhypopit, vomiting and diarrhea)  met the criteria for septic shock. He had fever, tachycardia (SIRS) and hypotension.
You met the recognition in 5 minute goal!
You met the IV access in 5 minute goal!
You met the 60cc/kg in 60 minute goal for IVFs!
You met the antibiotics in 60 minute goal!
You met the pressor initiation at 60 minute goal!
A final change hypothesis included personal feedback and this allowed for accountability for individual providers. Individual accountability is a key component of any quality intervention.

51. MEASURE: Run Chart
The run chart allows us to learn about the performance of a process with minimal statistical complexity. Specifically, it provides a simple method to determine if a process is demonstrating non-random patterns. The x axis represents time and the y axis represents the measure one is interested in.

52. MEASURE: SPC Chart Upper Control Limit Lower Control Limit
However, run charts are not capable of determining if a process is stable, ie if there is variation in a process a regular run chart will not pick it up. One must use an statistical process control chart or Shewart chart.
Essentially the normal curve is flipped on its side and upper and lower control limits (click for animation) are calculated using several software applications. One can then plot adherence rates or whatever it is being measured over time.
As soon as a point goes above the upper and lower control limit lines something has arisen from a a special circumstance that needs to be investigated.

53. Example SPC chart
This is an example of a statistical process control chart demonstrating improvement after the initial intervention.

54. The Improvement Guide: 1996
Further PDSA cycles will now have to be carried out, acting on the information gathered from the first cycle.
The Improvement Guide: 1996

55. Sepsis and Septic Shock
Early, timely goal directed therapy improves patient outcomes and mortality
A systematic approach is necessary for a successful quality improvement project