sepsis

Hey CTU.

I just wanted to post some of the information we covered about sepsis in case you wanted to give it a second look.  Some good references are linked throughout the text. Here is a link for current guidelines- click here
 

Why do we care?

Mortality rate is around 1/3 with severe sepsis

SIRS (2/4):

1.     HR > 90

2.     Temp. < 36 , > 38

3.     Resp rate > 20 or pCO₂ < 32

4.     WBC > 12 000 or < 4000

Sepsis:

Inflammatory reaction (SIRS) + probable evidence of infection

Severe Sepsis:

Sepsis + plus signs of hypoperfusion. i.e hypotension, oliguria ( < .5 ml/kg/hr), elevated lactate, elevated creatinine, elevated bilirubin, hypoxia

Septic Shock:

Sepsis + signs of hypoperfusion despite adequate resuscitation

So how do we resuscitate?

Based on Rivers 2001, NEJM (Rivers paper link)

·      RCT in one centre in Detroit, sample 263 with severe sepsis or worse

·      Randomized to early goal directed therapy v. usual care

·      Mortality 46.5 v. 30.5 %

·      Attempted to meet certain benchmarks within 6 hours of admission

1.     Inserted lines

2.     CVP 8 -12 mm Hg with fluids (CVP is pressure in SVC near R. atria = JVP + ~5 cm)

3.     MAP > 65 mm Hg with vasopressors preserves perfusion (MAP = 2/3 diastole + 1/3 systole)

4.     Scv0₂ < 70 %? (N.B Superior vena cava 0₂ saturation), check hematocrit!

Scv0₂ is a measure of how much oxygen is in blood after passing through body, so it could be low to either not enough delivery or too much consumption. We need to ensure enough delivery of oxygen to tissues.

a.     < 30 %, transfuse pRBCs

b.     > 30 %, use inotropic agents (in this case dobutamine)

·      So bottom line: using a protocol with hard outcomes works!

We try to do this, also target:

1.     Urine output > .5 ml /kg/hr

2.     Normalizing lactate, can be used instead of ScvO₂ , target >20% decrease in 2 hrs

Now we are thinking about resuscitation, what else should we be doing?

Treating the underlying infection!

1.     Diagnosis à head to toe: encephalitis, meningitis, ENT, influenza, pneumonia, GI, GU, hepatobiliary, skin, deep tissue, osteomyelitis, heart

·      Hx  / Physical

·      Imaging

·      Cultures (minimum 2 sets, peripheral and central)

·      Treat (within one hour is optimal): broad spectrum, generally combination therapy because better outcomes in the sickest patients (due to resistance?)

·      N.B: each hour delay increases mortality by 8%

Some Issues:

1.     What fluid should we use?

·      Remember Interstitial ¾ + Vascular ¼

·      Normal saline is salt water, it moves from intravascular to extravascular space according to Starling Forces: hydrostatic and oncotic pressure

·      Colloids are molecules that are too big to cross semi permeable membrane from vessels to interstitial space

·      Crystalloids: normal saline (Na 154 , pH 5.5), Ringer’s lactate (Na 131, lactate, K, Ca, pH 6.5)

·      NS is acidic because the ions decrease the concentration of CO₂ in blood.

·      Colloids: Albumin, Hydroxyethyl starch (HES)

·      Albumin has been shown to be SAFE (see SAFE study, link) in comparison to crystalloids, and may be better in severe sepsis (not a primary outcome)

·      HES have been shown to not offer much benefit compared to crystalloids and may cause harm (see CHEST study, link) as it leads to more RRT (renal replacement therapy)

2.     Which pressors should we use?

·      Norepinephrine is first choice (mainly vasoconstriction) compared to dopamine in meta-analysis, 2-40 mcg/min

·      Epinephrine is a great adjunct as no evidence of worse outcomes (theoretical splanchnic vasoconstriction), 1-20 mcg/min

·      Dobutamine is the first line ionotrope for low cardiac output

3.     Should we use corticosteroids?

·      Not in the initial resuscitation phase

·      Evidence is mixed. Major trial is CORTICUS (link): no mortality benefit, but not only patients non-responsive to pressors, and probably a less sick cohort

·      If resuscitation resistant shock trial IV hydrocort 200 mg/day

·      ACTH stimulation test not useful for deciding who to treat

4.     What is our hemoglobin level?

·      Our goal is a hb of 70, based on TRICC trial (link): transfusion level of 70 v 100 with no difference in mortality.

5.     Should we have tight glucose control?

·      We should aim for blood sugars between (10 - 6) to avoid hypoglycemia

·      Initial trial (leuven protocol) found reduced mortality with tight control (4-6)

·      NICE-SUGAR trial (link)found increased mortality with tight control from hypoglycemia

·      Subsequent meta-analyses have differed, may be due to sugar level of controls in each study

6.     Should we be using bicarbonate?

·      No if pH is > 7.15, as this has been studied in two small RCTs

·      Unclear if should be used in pH < 7.15. Remember bicarb will complex with hydrogen to make CO₂ and H₂O, and CO₂ can enter cells and cause worsening acidosis

Great Reference for Hemodynamic Parameters!

Link:
Normal Hemodynamic Parameters and Laboratory Values-Adult Patients

Necrotizing Pancreatitis!

We recently discussed Acute Pancreatitis along with some of it's local and systemic complications. Here is an article on Necrotizing Pancreatitis!

Perspectives in Clinical Gastroenterology & Hepatology

Treatment of Necrotizing Pancreatitis. 2012;10:1190-1201

Van Brunschot, S. et al. 

Treatment of Necrotizing Pancreatitis

Status Epilepticus

We recently discussed our approach to seizures, and reviewed the definition and management of seizures and status epilepticus. Here is an interesting read from Neurocritical Care:

Guidelines for the Evaluation and Management of Status Epilepticus

Gretchen M. Brophy et al.

 Neurocritical Care Society Status Epilepticus Guideline Writing Committee

http://www.neurocriticalcare.org/sites/default/files/pdfs/SE%20Guidelines%20NCS%200412.pdf

Guillain-Barre Syndrome (GBS)

Guillain-Barre Syndrome (GBS)

·    

•      Epidemiology: 1-2 per 100,000 per year; M>F
•      A heterogenous disease, with different variants; 
•         i.e. Miller Fisher syndrome — The typical presentation of MFS is that of ophthalmoplegia with ataxia and areflexia

Clinical Features: progressive, fairly symmetric muscle weakness accompanied by absent or decreased deep tendon reflexes (DTRs). Patients usually present a few days to a week after the onset of their symptoms. The weakness is variable (i.e. mild difficultly with walking to nearly complete paralysis of all extremity, facial, respiratory, bulbar muscles, etc).

·       

•      The weakness usually starts in the legs (NOTE: in 10% of patients, weakness starts in the arms or face)
•      Severe respiratory muscle weakness necessitating ventilator support occurs in 10-30%
•      Paresthesias in the hands and feet accompany weakness in >80% of cases
•      Pain (often in the back and extremities) can be presenting feature in the acute phase
•      Dysautonomia: tachycardia, urinary retention, HTN alternating with hypotension, orthostatic hypotension,  bradycardia, other arrhythmias, ileus, loss of sweating, etc. This can be associated with sudden death
•      Unusual Associations: SIADH, hearing loss, vocal cord paralysis, etc 

Course: progresses, usually over 2 weeks. At 4 weeks after the initial symptoms, 90% of patients have reached the nadir of their disease

Pathogenesis: thought to result from an immune response to a preceding infection that cross-reacts with peripheral nerve components because of molecular mimicry (immune response can be directed toward myelin or the axon of the peripheral nerveà resulting in demyelinating and axonal forms)

·       
       Most commonly identified precipitant: Campylobacter jejuni

o   Other: CMV, EBV, HIV

o   Triggers: after a immunization, surgery, trauma, bone marrow transplant

Investigations: diagnosis is confirmed with CSF and NCS/EMG; always do an LP!

1.LPàCSF: elevated protein with a normal WBC count (albuminocytological dissociation)—in up to 66% of cases, at 1 week after symptom onset

·       Elevated protein: may be due to increased permeability of the blood brain barrier (BBB) at the level of the proximal nerve roots

NOTE: a CSF pleocytosis is common in patients with GBS and HIV

2.EMG & NCS: help confirm diagnosis and provide prognostic info

Diagnostic criteria for GBS from the National Institute of Neurological Disorders and Stroke (NINDS) – based on expert consensus

• Progressive weakness of >1 limb, ranging from minimal weakness of the legs to total paralysis of all four limbs, the trunk, bulbar and facial muscles, and external ophthalmoplegia 
•  Areflexia (universal areflexia is typical): distal areflexia with hyporeflexia at the knees and biceps will suffice if other features are consistent.

Supportive features include:

•   Progression of symptoms over days to four weeks

•   Relative symmetry

•   Mild sensory symptoms or signs

•   Cranial nerve involvement, especially bilateral facial nerve weakness

•   Recovery starting two to four weeks after progression halts

•   Autonomic dysfunction

•   No fever at the onset

•   Elevated protein in CSF with a cell count <10/mm³

•   Electrodiagnostic abnormalities consistent with GBS

MANAGEMENT

*SUPPORTIVE CARE: up to 30% develop NM respiratory failure, requiring ventilation. Patient ought to be monitored for autonomic dysfunction (i.e. cardiac, respiratory, hemodynamic instability)
-PT/OT, wound care, DVT prophylaxis
-Adequate pain control

*RESPIRATORY FAILURE
-Vigilance is essential (deterioration can occur rapidly). Respiratory failure is common: 15-30% require ventilator support
-Measure vital capacity (VC) frequently; often measure Maximun Inspiratory Pressure (MIP) and Maximum Expiratory Pressure (MEP)

o   Warning, indication for intubation: FVC<20 mL/kg, MIP <30 cm H20, MEP<40 cm H20

·       -Bulbar dysfunction with swallowing problems and inability to clear secretions may add to the need for ventilator support

*AUTONOMIC DYSFUNCTION: dysautonomia occurs in 70% (i.e. tachycardia is the most common), urinary retention, hypertension/hypotension, bradycardia, orthostatic hypotension, ileus, arrhythmias, loss of sweating

*CARDIOVASCULAR MONTIORING: HR, BP, maintain intravascular volume

• Arrhythmias often occur with suctioning
• Avoid drugs that can drop BP
• Keep in mind that PLEX can cause hypotension and electrolyte abnormalities
•  Hypotension can be treated with IVF & phenylephrine (a pure alpha agonist!!)

*PAIN CONTROL: Neuropathic pain occurs in up to 50%

o   NSAIDS (don’t often work); consider gabapentin, carbamazepine

DISEASE MODIFYING TREATMENT: PLEX & IVIG

·       Plasmapharesis: removes circulating antibodies, complement & soluble biological response modifiers

o   Earlier improvement in mm strength, reduced need mechanical VE, better recovery

o   MA: most effective when started within 7 days of symptom onset

·       IVIG: precise MOA unknown; may provide anti-idiotypic antibodies, modulating expression and function of Fc RC, interfering with activation of complement & production of cytokines, interfering with activation and effector functions of T and B cells

o   As effective as PLEX

American Academy of Neurology (AAN)

o   Treatment with PLEX or IVIG hastens recovery from GBS

o   The beneficial effects of PLEX and IVIG are equivalent

o   Combining the two treatments is NOT beneficial

o   Glucocorticoid treatment alone is NOT beneficial

     Population:

o   PLEX: for non-ambulatory pts with GBS who start tx within 4 weeks of initial neuropathic symptoms;

o   For ambulatory pts who start tx within 2 weeks of onset of neuropathic sx

§  4 to 6 treatments, over 8-10 days; Side Effects- hypotension, sepsis, IV access issues

o   IVIG: non-ambulatory pts with GBS who start tx within 2 or possible 4 weeks of onset

o   0.4 mg/kg IV per day x 5 days. SE- aseptic meningitis, rash, AKI, rarely hyperviscosity

OUTCOME

• Poorer Prognosis: older age, rapid onset (<7 days), severe muscle weakness on admission, need for ventilator support, etc
• In the absence of disease modifying treatment, most patients show continued progression for up to 2 weeks, followed by a plateau phase of 2 weeks, then recovery phase (months)
• Disease Modifying treatment shortens time to walking by 50%
• Even with treatment, 5-10% have a prolonged course with very delayed and incomplete recovery

o   5% die despite intensive care

o   Relapses in 10%

IMMUNIZATIONS

o   AVOID in the acute phase of GBS and they are NOT suggested for 1 year or more after the onset of GBS

o   Future avoidance is suggested for any particular immunization that is followed within 6 weeks by the onset of GBS

RESOURCES: 
Indian Academy of Neurology. 2011 July; 14 (Suppl1): S73-S81. Treatment Guidelines for Guillain-Barre Syndrome. Meena, et al.
Treatment Guidelines for Guillain-Barre Syndrome