LMHER May 31, 2016 Prepared by Shane Barclay Sepsis update LMHER May 31, 2016 Prepared by Shane Barclay

Objectives Review the 2016 Sepsis 3 guideline definitions. Review the current sepsis protocol/treatment guidelines. Practice scenario of sepsis.

Sepsis definition Medical definitions of a disease should provide two goals: Provide rapid screening. Provide a definitive diagnosis. To date, neither of these goals have been very well achieved by sepsis definitions.

Sepsis definition 2016 Definition of sepsis: ‘a potentially life threatening organ dysfunction due to dysregulated host response to infection’. Does this provide a rapid screening or enable a definitive diagnosis?

Sepsis definition The original ‘definition’ of sepsis came out of a 1991 consensus meeting of the American College of Chest Physicians/Society of Critical Care Medicine (ACCP/SCCM). This is now known as the ‘SIRS 1’ Definition.

SIRS Stands for Systemic Inflammatory Response Syndrome, which was thought the be the pathophysiological process underlying Sepsis. SIRS Criteria: 2 of the following: Temperature > 38 degrees or < 36 degrees Heart Rate > 90 Respiratory rate > 20 or PaCO2 < 32 mm Hg WBC > 12,000 or < 4,000 or > 10% bands

Then came the ‘modified Sirs’ criteria Temperature > 38 degrees or < 36 degrees Heart Rate > 90 Respiratory rate > 20 or PaCO@ < 32 mm Hg 4. MAP < 65 5. New altered mental status 2 or more of these, plus suspected infection = sepsis

Then came the ‘modified Sirs’ criteria The problems was that this was defined more for research protocols that clinical use. Even using the modified SIRS, you will miss 1 in 8 patients with severe sepsis.

And now ‘Sepsis 3’ Definition Sepsis 3 came out of a consensus group in 2015. JAMA. 2016 Feb 23;315(8):801-10

‘Sepsis 3’ Definition Organ dysfunction under the new sepsis definition is defined as an increase of 2 points or more in the ‘Sequential Organ Failure Assessment’ (qSOFA) score: Hypotension: SPB < 100 mmHg Altered Mental Status (any GCS < 15) Tachypnea: RR > 22 With suspected infection.

Patients with 2 SOFA points denotes an overall mortality rate of 10% ‘Sepsis 3 Definition Patients with 2 SOFA points denotes an overall mortality rate of 10%

‘Septic Shock’ Definition Septic shock is now defined as a subset of sepsis wherein there is ‘sepsis’ as described previously AND both: Persistent hypotension requiring vasopressors to keep MAP > 65 and Lactate greater than 2 mmol/l Under these parameters, mortality is over 40%.

The problem with these ‘definitions’ The issue with all the ‘sepsis’ definitions is that they are consensus definitions using what has been called “threshold decision making”. They use biomarkers to predict sensitivity and specificity. They do not actually define what sepsis is from a clinical basis. In many ways they are merely predictors of mortality.

The Problem with sepsis definitions

The Problem with sepsis definitions

Sepsis 3 In short, Sepsis 3 criteria really only increased the specificity of predicting mortality while decreasing sensitivity from SIRS. And overall sensitivity of Sepsis 3 for patients OUTSIDE of the ICU is less than 55%.

Lactate ? The authors of Sepsis 3 determine that lactate measurement did not improve the predictive validity of qSOFA but might be helpful in identifying patients at ‘intermediate risk’?

Some of the problems with Sepsis 3 Fever and other SIRS criteria have a low specificity. There are no clinical signs of sepsis. Elderly, immunocompromised and malnourished patients often do not manifest signs of sepsis or SIRS. Some of the ‘clinical criteria’ apply to adult physiological variables. Actual infection may never be confirmed. qSOFA has never been prospectively validated.

Some of the problmes with sepsis 3 Increases in WBC is a marker of stress not just infection. Biomarkers such as CRP, procalcitonin, IL-6 have limited sensitivity and specificity and cannot/should not be used in isolation.

Sepsis is a dynamic process Sepsis is a dynamic condition and none of the prior nor current ‘definitions’ account for change in time. As well, all the criteria for ‘diagnosing’ sepsis may not be present at a single time in any one patient.

The problem with these ‘definitions’ There are really two categories of medical diagnosis definitions: Static Dynamic

The problem with these ‘definitions’ Elderly woman falls on outstretched hand at 9:08 am:

The problem with these ‘definitions’ This is a ‘static’ diagnosis. You know exactly when the ‘medical condition’ happened…9:08 am However what if the same woman presented with a 2 - 3 day history of mild fever, malaise, decreased appetite, changes in her mentation. She may be on a ‘continuum’ if infection/sepsis.

The problem with these ‘definitions’ Single bacteria invading body Sepsis, shock and death

So what can we conclude? There needs to be a highly sensitive screening test for sepsis. There needs to be a highly specific confirmatory test for sepsis. There needs to be some means of collating continuous data on a suspected patient rather than an ‘all or none’ dichotomous diagnosis. To date there are none of these.

Bottom line Consider sepsis as a possible cause whenever a patient develops new organ dysfunction. If you suspect sepsis, but qSOFA criteria are not met, do not withhold therapy. If qSOFA criteria are met, there should be prompt consideration of infection, further investigation and definite sepsis management initiated.

Current approach to Sepsis treatment

Sepsis treatment Give supplemental oxygen, monitor response via SpO2. Start antibiotics early and pick appropriately. Do blood cultures, MSU, CXR and other swabs/tests as appropriate. 3. Give fluids, but usually no need to exceed 2 - 3 liters. If BP is still ‘soft’ after 3 liters, consider pressors, not more fluid. Consider vasopressors anytime you suspect pulmonary edema developing 4. Be prepared for hypotension, either have pressors ready or started ahead of time. Even ONE episode of transient hypotension can be a warning sign of impending hypotensive crisis.

Sepsis treatment 5. Choice of pressor? Usually use norepinephrine infusion. If patient has tachycardia or arrhythmias then consider phenylephrine. 6. If still hypotensive after vasopressors, you can consider inotropic therapy with Dobutamine. 7. Try NOT to intubate. Patients are hypercapnic (helps venous return) and hyper-adrenergic (maintains their blood pressure). If you sedate/intubate you take away this and they can crash. 8. If you need to intubate use ketamine and have a pressor ready.

Types of shock

Sepsis treatment 11. Remember, sepsis is a state of hypotension of the ‘distributive type’ (ie not pump failure, hypovolemia etc). The resulting vasodilation that occurs causes hypoperfusion. However with sepsis, you can have hypoperfusion without hypotension. 12. In early sepsis, the skin may be warm and flushed. As sepsis progresses the skin may become cool and pale.

Sepsis treatment 13. Use lactate as a marker of severity. Lactate > 2 mmol/L can be a sign of organ hypoperfusion in the absence of hypotension. Lactate > 4 mmol/L can be (but is NOT diagnostic of) a sign of severe sepsis. There is debate as to what constitutes ‘appropriate’ lactate clearance. Generally speaking if it doesn’t drop after 6 hours or if it has risen, then this should prompt a reevaluation of the patient’s perfusion status. Once perfusion is established, lactate is a poor marker of tissue perfusion.

Questions ?

Scenario A 68 year old male presents to the ER with a 2 day history of chills, mild fever and urinary frequency. He tells you he is awaiting surgery on his ‘big prostate’. Past history: Type 2 diabetes, HTN, BPH, mild intermittent claudication. On exam: BP 125/70, HR 100/min, RR 25/min. Temp 37.7 He is alert and oriented. He tells you his blood pressure is usually around 140/85. He feels warm and his face is flushed but his hands feel cool.