Sepsis Flashcards
Define sepsis and septic shock
Sepsis is life-threatening organ dysfunction caused by a dysregulated host response to infection
Septic shock is a subset of sepsis with circulatory and cellular/metabolic dysfunction associated with a higher risk of mortality
Give a broad overview of the recomendation of suriviving sepsis campain (headings)
a) initial resus
b) Screening for sepsis
c) diagnosis
d)anti-microbial therapy
e) source control
f) Fluid therapy
G) vaso active medications
h) corticosteroids
I) blood products
J) immunoglubolins
k) blood purification
l) anticoagulatnats
m) mechanical ventilation
n) sedation and analgeisa
O)glucose control
p) renal replacement therapy
q)HCO3 therapy
r) VTE prophylaxsis
s) Stress ulcer prophylaxis
t) nutrition
Discuss intitial resuscitation of sepsis as per surviving sepsis
1) at least 30ml/kg bolus of crystaloid to be given within the first 3 hours – with guidance for further fluids by HD assessment
2) HD assessment and exam to ascertain cause of shock - use dynamic over static varibales for assessment of HD. Dynamic variables include (passive leg raise, fluid challenges against Stroke volume measurement or the variation in systolic pulse pressure or SV to chanbes in intrathoracic pressure induced by mechanical ventilation )
3) Target MAP of 65 for initial resus – nil improvement in mortality with higher MAP target but increase in arrythmias
4) Guide reuss to normalise lactate in patient with eleaveted lactate levels as a marker of tissue hypoperfusion
ABs as soon as possible – appropriate choice – consider candida in immunocompromised host
Culture before as long as not delaying antibiotics 30-40 minutes
AIM map 65
Discuss consideration for initial emperically ABs
a) The anatomic site of infection with respect to the typical pathogen profile and to the properties of individual antimicrobials to penetrate that site
b) Prevalent pathogens within the community, hospital, and even hospital ward
c) The resistance patterns of those prevalent pathogens
d) The presence of specific immune defects such as neutropenia, splenectomy, poorly controlled HIV infection and acquired or congenital defects of immunoglobulin, complement or leukocyte function or production
e) Age and patient comorbidities including chronic illness (e.g., diabetes) and chronic organ dysfunction (e.g., liver or renal failure), the presence of invasive devices (e.g., central venous lines or urinary catheter) that compromise the defense to infection.
Describe why mitochondria are the canaries of sepsis
Highest oxygen tension in the body - more than 95% of aerobic chemical energy comes from mitochondria. They are affected first in conditions of inadequate tissues perfusion. The cell then catabolizes fuels to lactate
Discuss major pathogens causing sepsis in children under 2months and those in children over 2 months
Under 2 (GELS + HSV)
- Escherichia coli
- Group B Streptococcus
- Listeria monocytogenes is uncommon
- HSV infection should be considered in differential diagnosis of sepsis
Over 2
- Neisseria meningitidis
- streptococcus pneumoniae
- Staphylococcus aureus (MSSA or MRSA)
- Group A Streptococcus (GAS)
Discuss time wise approach to a septic child
Within the first 5 minutes
- appropriate hands and environment
- Attach monitoring
- Address airway or breathing issues
- apply oxygen if required
Within 15 minutes
- Access whether IV or IO
- Bloods (Cultures x2, VBG with lactate and Glucose as prioity) Then fbc, u&E, LFT, coags, crp - urine and Puncture
- Administer Abs – consider IM if access difficult
Within 30 minutes
- Fluid bolus 20ml/kg normal saline repeat 10ml/kg boluses as needed upt to 40ml/kg - repeat fluid monitoring
- caution if worsening with fluids to consider heart failure or myocarditis
- Consider inotropes early if non responsive to fluids
Within 60 minutes
- start inotropes for persistant circulatory failure after 40ml/kg
- 0.05-0.2mic/kg adrenaline
- made 6mg in 1000ml 0.9% 1ml/kg/hr = 1mic/kg/min
Discuss antibiotic chose for children under 2months and for those over 2 months (Meningitis exclude)
Under 1 month
Amp 50mg/kg q12hourly + Gent 5 mg/kg up to 320mg + Vancomycin IV 15mg/kg/dose every 6 hourly
Under 1-2 months
-Amp 50mg/kg q6hourly + Gent 7.5 mg/kg up to 320mg + Vancomycin IV 15mg/kg/dose every 6 hourly
Over 2 months
- Ceftriaxone 50mg/kg 6 hourly + Vancomycin
or - cefotaxime 50mk/kg
If menigitis suspected in children under 2 months
- Ceftriaxone 50mg/kg + ampicillin 50mg/kg
If HSV suspected add 50mg/kg of aciclovir
Discuss the physiology of hemorrhagic shock in a healthy patient
Rapid haemorrhage generally leads to an increase in heart rate and cardiac contractility followed by activation of baro-receptors and peripheral vasoconstriction.
This leads to a rise in the diastolic pressure, narrowing of the pulse pressure and initial maintenance of the systolic
Blood flow directed away from non critical organs leads to the production of lactic acidosis. This is generally compensated for initially preventing acidosis. Earliest sign of significant bleeding can be the base access which is usually more +ve than -ve2 – under.
Brainstem chemoreceptors are activated leading to increase in resp rate and a decrease in arterial co2
With progressive blood lose these cardiovascular reflexes are overcome and systemic hypotension occurs. Coincidentally the buffer systems are overcome leading to acidosis
Commonly otherwise well patients with significant bleeding will have a lactate greater than 4, pco2 <35 and mild hyperglycaemia for stress hormones and mild hypokalaemia
Discuss second phase of organ injury from haemorrhagic shock
occurs from inflammatory mediators released after resus
Neutrophils become more aggressive to the endothelium and cause capillary leakage that characterises ARDS
Inflammatory cytokines are liberated causing additional cellular damage and compunded by persistant microischaemic caused by an imbalnce between nitrous oxide and endothelins
A growing body of evidence suggest that resus causes greater strain on the heart than the initial hypotensive injury
What are the three major affects that are caused by septic shock and need to be addressed in resus
1: Relative and absolute hypovolaemia
- - Absolute hypovolaemia occurs due to GI loss increase in insensible losses (tachypnoea, sweating) and decreased oral intake
- - Relative hypovolaemia occurs due to increase in capacitance vessels in conjunction with leaking capillaries and third space loss
2: Depressed cardiac function
- Cardiac contractility becomes impaired early in the course of sepsis even in the hyperdynamic phase
- circulating mediators, deranged metabolic interactions and specific cytokines (TNF A, ILB) act synergistically to injure the heart ‘
3) disregulated immune system
- aggressive neutrophils cause leaky capillaries and can lead to ARDS
- widespread inflammatory mediators play a role in the development and persistence of MOF
Discuss cardiogenic shock
Results when more than 40% of the myocardium becomes dysfunctional from ischaemia, inflammation, toxins or immune injury
Otherwise physiological response is similar to that of hemorrhagic shock -
Discuss neurogenic shock
is due to interrupted sympathetic and parasympathetic pathways from the spinal cord to the heart and peripheral vasculature usually from trauma
classically peripheral vasodilation and hypotension with bradycardia
given variable location and balance between dysrupted efferent sympathetic and paraympathetic tone can vary in degree of heart and hypotension
Discuss optimal dosing strategey for aminoglycosides and fluroquinolones
Peak concentration that matters
once daily dosing for aminoglycosides has similar efficacy and reduced toxic effects
An approacht that optimises the dose within the non toxic range should provide the highest probabiliy of facorable microbiological and clinical response
Discuss optimal dosing for B lactums
Key PD correleate to microbiological and clinical response is time that the plasma concentration of the drug is above the pathogen MIC. A minimun T>MIC of 60% is generally sufficient to allow a good clinical response for mild to moderate disease.
Discuss combination antibiotic choice in septic shock as per Sepsis 3
For septic shock empiric combination therapy (using at least two different antimicrobial calsses) aimed at the most likley bacterial pathogens for the initial management of septic shock – often used to increase clearance of a specific pathogen which is suscpected to be sensitive to both ABs
Do not continue combination therapy for ongoing treatment of serious infection including bacteremia and sepsis without shock
Dont use combination antibiotics for neutropenic sepsis.
De-escalation from combincation therapy within the first few days guided by patient improvement or rationilising of ABs
Due to increasing frequency of pathogen resistance ot anitmicrobials multidrug therapy is often required to ensure an appropriately broad spectrum of coverage
Define an uncomplivated bacteremia
1) exclusion of endocarditis
2) no impanted prostheses
3) negative follow-up BC drawn 2-4 days after the initial set
4) defervescence within 72 hours after the initation of effective antibiotic therapy
5) no evidence of metastatic infection
Discuss source control
As prompt as possible
Without appropriate source control some more severe presentation will not stabilize or improve despite appropriate ABs and resus
Discuss fluid therapy in sepsis
1) -It is reccommended that fluid challenge technique be applied where fluid administration is continued as long as HD factors continue to improve.
2) -crystaloids as a choice of fluid
3) - either balanced crystaloid or saline for fluid resus - nil direct comparison studies - one before and after showed increase in AKi and RRT in chloride liberal strategy
4) - use albumin in addition to crysaloid for intiial and subsequent intravascular replacement in patient with sepsis and septic shock when substantial amounts of crystaloid are neded - SAFE study showed albumin was safe and equally effective as normal saline
5) Dont use hydroxyehtel starches
Discuss fluid therapy in sepsis
1) -It is reccommended that fluid challenge technique be applied where fluid administration is continued as long as HD factors continue to improve.
2) -crystaloids as a choice of fluid
3) - either balanced crystaloid or saline for fluid resus - nil direct comparison studies - one before and after showed increase in AKi and RRT in chloride liberal strategy
4) - use albumin in addition to crysaloid for intiial and subsequent intravascular replacement in patient with sepsis and septic shock when substantial amounts of crystaloid are neded - SAFE study showed albumin was safe and equally effective as normal saline
5) Dont use hydroxyehtel starches
Discuss the use of vasoactive medications
1) norad as the first choice of vasopressure
2) vasopressin (up to 0.03U/min) or epi as next agent to increase MAP or decrease norad dose
- vasopressin levels in spetic shock have been reported to be lower thatn anticipated for a shock state
- Vasopressin may be effective in patients refractory to other pressors and have other physiological benefits
- vasopressin is elevated early in septic shock than reduces to normal levels (relative vasopressor defiency)n
3) Can use dopamine as an alternitive vasopressor to norad in only a very specific subset of people ( lor risk of tachyarrythmias and absolute or relative bradycardia)
4) Dont use low dose dopamine for renal protection (dopamine is more arrhythmogenic)
5) use dobutamine in patient with persistent hypoperfusion despite adequate fluid loading and the use of vasopressors – this is used if suspected myocardial dysfunction in the setting of infection
- alternatives to dobutamine are the phosphodiesterase inhibtoe which increased CAMP and those have inotropic effect independant of B agonists.
- These include milrinone and levosimendan
- Nil evidence to support superioty of levi to dobutamine and is more expensive and less widely availble.
Everyone on pressors or inotropes should have invasive monitoring - lower rates of complications with US and radial artery use
Discuss the use of corticosteroids in Sepsis
1) suggest against the use of IV hydrocort in septic shock if able to restore HD stability with fluids and inotropes - if not possible suggest IV hydrocort at a dose fo 200mg per day
Nil convincing evidence with contradictory meta-analysis
Theoretically works in vasopressor non responsive shock by addressing relative adrenoinsufficiency and adressing corticosteroids permissive effects to norad and adrenaline
Random cortisol levels can be useful to identify absolute adrenoinsuffiency but are not effective in identifying relative insuffiency
Hyperglycaemia and hypernatraemia can be side effects
- need to ween
Discuss blood product use in sepsis
1) transfusion threshold for HB is 70mg/dk
2) Reccomend against EPO
3) Dont use FFP to correct clotting abnormalities in teh absence of bleeding or planned invasisve procedures
4) Prophylactic platelet transfusion at 10 in the absence of apparent bleeding and 20 if the patient has a risk of bleeding. Higher counts >50 for active bleeding, surgery or invasive procedures.
Discuss the use of immnoglobulins in Sepsis
Poor evidence at present but nil role of IVIG in patients with septic shock
