Key facts:
Author: Sabina Moolla
Top Tip: Lack of temperature and/or normal/low WC can indicate a worse prognosis; also, lack of hypotension does not exclude diagnosis
Key Differential Diagnoses
- All causes of hypotension or shock (esp. hypovolaemia, cardiogenic shock, anaphylactic shock)
- Drug fever
- Vasculitis
Key Investigations
- BC
- Lactate (ABG, you need this as part of 'sepsis six')
- Urinalysis, MSU
- FBC, Clotting (DIC?), ESR, CRP
- U+E, LFT, Bone, Glucose, Amylase
- ECG, CXR
Key Treatment
Sepsis Six:
- High flow oxygen
- BC
- IV antibiotics within one hour
- Fluid resuscitation
- Lactate and Hb
- Catheterise, if necessary - and monitor urine output
Followed by Early Goal-Directed Therapy
Key Management Decisions
- ITU/ventilation – does patient need inotropic or ventilatory support?
- Source control (eg drainage of abscess or removal of foreign body)
Background
Hypotension, despite adequate fluid replacement, with no obvious cardiac cause, is an ominous sign; and should be be considered due to severe sepsis until otherwise proven, whatever the temperature and/or WC
Introduction
- Sepsis is defined as the presence or presumed presence of an infection accompanied by evidence of a systemic response (called 'systemic inflammatory response syndrome', SIRS, which is now being replaced by ‘Signs and Symptoms of Infection’, SSI)
- Severe sepsis is a common and commonly fatal disease and is essentially an exaggerated inflammatory response
- It has a high mortality (25-80%; ITU >50%)
- The Surviving Sepsis Campaign (see references) is trying to make us focus more on patients with serious infection
- Intravenous antibiotics should be given within 1h of diagnosis
- The prescription should be reviewed at 48h when results of cultures are to hand, and changes made if patient is not improving
[Ref] - Hypotension, tachycardia (bounding pulse), with warm peripheries, are hallmarks of severe sepsis; this is due to vasodilatation - making patient appear more well than they are
Definitions
- Bacteraemia = positive BC; but absence does not exclude diagnosis of:
- SIRS (systemic inflammatory response, aka SSI (symptoms and signs of infection))
= 2 or more of:
• Temperature >38.3°C or <36°C
• Heart rate >90
• Respiratory rate >20 or PaCO2 <4 kPa
• WC >12 or <4
• Acutely altered mental state
• Hyperglycaemia (without diabetes) - Sepsis = SIRS/SSI associated with documented or presumed infection
- Severe sepsis = sepsis associated with organ dysfunction + hypotension; and/or evidence of hypoperfusion including:
• SBP<90mmHg
• Urine output <0.5ml/kg/hr for 2hrs
• Lactate >2
• Need for oxygen to keep SpO2>90%
• INR>1.5
• Platelets <100
• Bilirubin >34
• Creatinine >177 - Septic shock = severe sepsis associated with hypotension (systolic blood pressure <90 mm Hg; or fall of >40 mm Hg from baseline), not responsive to fluid resuscitation
Note: to help you differentiate these syndromes, a screening tool (Sabina Moolla, 2007), pdf has been developed
Epidemiology
- Incidence 1/200,000 pa = 1000 pts admitted to every general or teaching hospital each year = ie 3/day
- Causes a third of hospital and intensive care unit bed days
>50% patients treated in hospital for severe sepsis are managed exclusively in general ward; and some elderly, chronically sick patients may be treated at home or in nursing homes - Mortality = 25-80% (>50% on ITU)
- Median hospital LOS = 18d; ITU length of stay (LOS) = 4-8d
Causes
- 50% respiratory
- 20% abdominal
- Rest = uro-genital sepsis, skin, bone, and soft tissue infections, and miscellaneous conditions, including meningococcaemia
- Multiple sites 10-15%
- Multiple organisms identified 10%
Risk factors
- Immunosuppression
- Chemotherapy
- Extremes of age
- DM
- Chronic failures (especially renal, liver)
Symptoms
- Very variable
- May be non-specific, or relate to the cause of sepsis
Key questions
- "When did you start feeling unwell?"
- "Is any other doctor treating you for any other serious disease at present?"
Signs
- Hypotension, tachycardia (bounding pulse), with warm peripheries, are hallmarks of severe sepsis
- Or, when more ill, can have cool peripheries (ie, do eventually become shut-down); with livedo reticularis type rash
- SOB (acidosis?)
- Listen to heart (murmurs?)
- Feel spine (discitis)
Note: severe sepsis can be present without hypotension, in fit young patients
Investigation
Blood
- BC essential
- FBC, ESR, CRP
- U+E, LFT, Bone, Glucose, Amylase, Clotting (DIC?)
- ABG – for lactate
Note: FBC and clotting may suggest DIC (guidelines regarding the diagnosis and management of DIC are in the references)
Other
- Urinalysis, MSU
- ECG
- CXR
- Sputum, stool (including C difficile) culture
Consider:
- LP
- Line tips (or foreign body), if removed
- If surgical: drain fluid, wound swab
- US abdomen (?collection, ?acalculous cholangitis)
- CT head, chest, abdomen (?emphysematous pyelonephritis) or pelvis, or combination
- ECHO (?endocarditis)
Key investigations
- BC (2 sets)
Differential diagnosis
- All causes of hypotension or shock (especially hypovolaemia, cardiogenic, hypoadrenalism, anaphylactic; can have more than one, eg hypovolaemia and sepsis)
- Drug fever
- Vasculitis (can have both, eg immunosuppression may cause severe sepsis)
Treatment
IV antibiotics should be given within 1h of the diagnosis; and, why are you not using O2, central line/inotropes, urinary catheter?
Treatment (first line)
Sepsis Six:
- High flow oxygen
- BC
- IV, within one hour
- Fluid resuscitation
- Lactate and Hb
- Catheterise, if necessary and monitor urine output
- Followed by Early Goal-Directed Therapy
- Central line – inotropic support. The use of routine corticosteroids is controversial: [Ref]
Key management decisions
- ITU
- Ventilation
Stop/reduce
- Immunosuppression, with knowledge of prescriber
Treatment (second line)
Drugs
- ?IV HYDRORTISONE 200 mg; 'nobody should die with low BP, without having been given 200 mg IV hydrocortisone' (ie is the patient hypoadrenal?)
Procedures
- Source control .. 'where there is pus, let it out'
- Ie, consider drainage of abscess or removal of foreign bodies; eg recent graft, prosthesis, cardiac valve, central line (after discussion with senior, and specialist team)
- Urinary catheter; maintain urine output > 0.5ml/kg/hr
- CVP line: large volumes (4-6L) of fluid may be required
Note: concerns over heart failure should not prevent adequate volume resuscitation; colloid and crystalloid are equivalent in terms of efficacy and adverse events - Arterial line
Maintain systolic BP at > 130 mmHg with fluids, noradrenaline (norepinephrine) and, if necessary, dobutamine - Ventilation:
If airway at risk, fails to respond to initial treatment or patient becomes exhausted or comatose, or develops ventilatory failure - Nasogastric tube
Prescribing issues
- Antibiotics are only part of the severe sepsis pathway; the other components are as or more important, especially fluid resuscitation
Admit?
- Almost always; unless returning to Nursing Home etc
Bed plan
- Medical Admission Ward
- ± Appropriate specialist ward
- ± ITU
Referrals
Medical
- Microbiology
- Infectious diseases, if available in your hospital
- Prescriber of immunosuppression/chemotherapy
- ITU
Other
- ITU outreach team, when leaves ITU, or if not taken
The Rest
Maxim No 1
- 'Nobody should die with low BP, without having been given 200 mg IV hydrocortisone'
Maxim No 2
- 'Where there is pus, let it out'
Complications
- Atrial fibrillation is common and may contribute hypotension
Note: fluid resuscitation and correction of electrolyte abnormalities takes precedence over antidysrhythmics
If not getting better, consider: - Abscess
- Wrong diagnosis
- Wrong antibiotic (eg, previosuly used by GP)
- Wrong dose
- Continued inflammatory response
- Advanced disease
- Viruses, fungi
Follow-up
- If on immunosuppression, within 2 weeks of discharge, with prescriber
Prognosis
- Mortality 25-80%; >50% ITU
Worse prognosis:
- Old
- Immunosuppression/chemotherapy
- Comorbidity
- Organ failure (3 = 70%, 4 = 80%, 5+ = 90%+)
- Hospital-acquired infection
- Leucopenia, hypothermia
- Gram negative organism
- Polymorphism for genes coding for elements of the inflammatory system
- Positive BC
- Hypoalbuminaemia
- DIC
[Ref]
2° Prevention + Health promotion
- If on immunosuppression/chemotherapy, report fever, and other symptoms, to prescriber ASAP
Don't forget
- Look for DIC
- Large volumes (4-6L) of fluid may be required
Note: concerns over heart failure should not prevent adequate volume resuscitation - Contact any prescriber of immunosuppression/chemotherapy ASAP
- Abscess (?operation), or wrong AB, if not getting better
- 200 mg IV hydrocortisone
Red flags
- Drowsiness
- Hypoxia
- Poor urine output
- Organ failure
