Resident Version
SIRS and Septic Shock
created by Dr. Dana Davis
Objectives:
1. Define and differentiate bacteremia and the clinical spectrum of SIRS, sepsis,
severe sepsis, and septic shock.
2. Identify typical choices for empirical antibiotics for patients with sepsis.
3. Identify patient groups with increased risk for the development of sepsis,
increased morbidity or mortality, or uncommon etiologic organisms.
4. Describe the indications, contraindications and side effects of therapeutic agents
including fluids, vasopressors, antibiotics, steroids, and activated protein C in the
treatment of sepsis.
References:
1. Lorente JA, et al, Time course of hemostatic abnormalities in sepsis and its
relation to outcome., Chest, 1993, May, 103(1536-42)
2. McGill, Endothelial cells: role in infection and inflammation. World J Surg - 01FEB-1998; 22(2): 171-8
3. Levi M, Disseminated intravascular coagulation. N Engl J Med - 19-AUG-1999;
341(8): 586-92
(antibiotics)
4. Bernard GR . Efficacy and safety of recombinant human activated protein C for
severe sepsis. N Engl J Med - 8-MAR-2001; 344(10): 699-709
5. O’Brien JM. New approaches to the treatment of sepsis. Clinics in Chest
Medicine. Volume 24 • Number 4 • December 2003
6. The International Sepsis Forum. Guidelines for the management of severe sepsis
and septic shock. Intensive Care Med 2001;27(Suppl. 1):S1–134.
7. Simon D, Trenholme G. Antibiotic selection for patients with septic shock. Crit
Care Clin. 2000;16:215–230.
8. Annane D, Sebille V, Charpentier C, Bollaert PE, Francois B, Korach JM, et al.
Effect of treatment with low doses of hydrocortisone and fludrocortisone on
mortality in patients with septic shock. JAMA 2002;288(7):862-71.
9. Briegel J , Forst H , Haller M , et al: Stress doses of hydrocortisone reverse
hyperdynamic septic shock : A prospective, randomized, double-blind, single-center
study . Crit Care Med 1999 ; 27 : 723–732
10. 14th European Congress of Clinical Microbiology and Infectious Diseases, May
1–4, 2004
11. Kumar A, Roberts D, Wood KE, et al. Delays in antimicrobial therapy for sepsis.
Crit Care Med. 2004;32:A11.
12. Surviving Sepsis Campaign guidelines for management of severe sepsis and
septic shock. Crit Care Med 2004; 32:85.
CASE
History:
33 y/o F presents with Fever, non-productive cough, sore throat and head ache. URI sxs
X 5 days. Came in b/c feeling tired and a little SOB. Not eating or drinking much. . 2
kids at home both of whom have had recent URI/sore throat about 2 weeks ago.
PMH
MVA  spleenectomy at age 9
Immunization status unknown
No medications
G2 P2
NKDA
ROS
Neg. except as reported in HPI
T 35.8 P 98 R 20 (PaCO2 will be 30) BP 100/56, O2 sat 91% RA
A&O X 4. Skin is dry.
HEENT – pharynx injected. Neck supple. No adenopathy
CV – no murmurs
Lungs – L posterior crackles
Abdomen – benign
Skin – no rash
Lymph – no adenopathy
Normal genital/rectal exams
No muscle or joint swelling.
WBC 24.5 (85 PMN - automated(15 Bands, 70 Segs), 5 lymphs, 10 monos), H/H
13.6/40, Plt 166 K
Chem 10 Na 148, K 4.6, Cl 105, Bicarb 24, BUN 22, Cr 1.2 , Ca 9.4, PO4 5, Mg 2.0
CXR – Possible LLL pneumonia
Hospital course:
Patient admitted to the hospital with suspected pneumonia in an asplenic patient. Initial
blood cultures were taken, as were sputum and urine cultures. Antibiotics were ordered
in the Emergency Room, but were delayed for approximately 2 hours. Initially she was
started on cefotaxime and doxycycline.
She was started on IV fluids, bolused with lL of NS and infused with 1/2 NS at 150 cc
per hour.
At the time that the antibiotics were being administered it was noted that her pulse was
now 110 to 124 and her blood pressure was 98/46. The patient was complaining of
worsening headache and photophobia. The remainder of her vitals were unchanged.
Suspecting meningitis a CT was performed which was normal.
An LP was performed.
Gram stain showed Gram positive diplococci. WBC count was 1500 with 200 RBC.
Glucose 44 and protein 88. At that time a call from the lab was received that the patient
was noted to have Gram + diplococci on her peripheral blood smear.
Vancomycin was added to her antibiotics and she was switched from cefotaxime to
ceftriaxone and was given a single dose of dexamethasone.
Two hours later the patient began to complain of bilateral leg numbness and weakness.
She was noted to have diminished strength in both lower extremities, as well as decreased
pinprick sensation and reduced sphincter tone. The exam was also significant for a pulse
of 138, BP of 86/42, she appeared mottled with multiple bruises where she had been
stuck for lab draws and IVs, and she was oriented to person only.
Repeat labs were ordered:
Chem 10 – Na 144, K – 4.9, Cl – 98, Bicarb – 20, BUN – 32, Cr – 1.6, PO4 – 2.2, Mg –
1.7
CBC - WBC 12.5 (15 Bands, 55 Segs, 5 metamyelocytes, 12 Monos, 13 Lymphs), H/H
– 11/33, Plt - 70
PT – 28 (INR 9.2), PTT – 65
LFTs – AST 108, ALT 114, Alk. Phos 88, Total Bili. 5.2, Direct Bili. 1.1, Albumin 3.6,
Total Protein 8.6
MRI of L / S spine showed hematoma present in lumbar spinal cord.
The patient was transferred to the MICU and dopamine was instituted. Shortly after
transfer the patient became hypoxic and required mechanical ventilation. A repeat CXR
showed diffuse “white out” consistent with severe ARDS.
The following day the patient developed unrelenting seizures. Once the seizures were
controlled with lorazepam and fosphenytoin a repeat CT scan was done which showed
intracerebral hemorrhage. The patient also had bilateral dilated pupils and lacked
brainstem reflexes.
After discussions with her family life support was withdrawn and the patient died shortly
thereafter. Autopsy was performed. The blood cultures and spinal fluid grew out
pneumococcus which was sensitive to ceftriaxone. The official cause of death was
determined to be pneumococcal sepsis resulting in coagulopathy and subsequent
intracerebral hemorrhage
Discuss management of this patient including use of fluids, antibiotics, pressors,
steroids as well as significance of results from lab/diagnostic tests.
Outline for discussion
Definitions:
1)Bacteremia – presence of viable bacteria in circulating blood
2)SIRS - is a widespread inflammatory response to a variety of severe clinical insults.
This syndrome is clinically recognized by the presence of two or more of the following:
Temperature >38ºC or <36ºC
Heart rate >90 beats/min
Respiratory rate >20 breaths/min or PaCO2 <32 mmHg
WBC >12,000 cells/mm3, <4000 cells/mm3, or with >10 percent immature
(band) forms
Non-infectious causes of SIRS
Trauma / burns (34 %)
CVA (6%)
GI bleeding (5%)
Pancreatitis, vaginal delivery, CHF, TTP, malignancies, acute coronary syndrome,
thromboembolism, and DKA.
SIRS + infection = Sepsis  Severe Sepsis  Septic Shock
3) Sepsis - This is a systemic inflammatory response to a documented infection. The
manifestations of sepsis are the same as those previously defined for SIRS.
4) Severe Sepsis - This is sepsis and SIRS associated with organ dysfunction,
hypoperfusion, or hypotension.
5)Septic Shock A subset of people with severe sepsis develop hypotension despite
adequate fluid resuscitation, along with the presence of perfusion abnormalities that may
include lactic acidosis, oliguria, or an acute alteration in mental status.
6) MODS (multiple organ dysfunction syndrome) This is the presence of altered organ
function in a patient who is acutely ill and in whom homeostasis cannot be maintained
without intervention.
Epidemiology:
Patient characteristics which increase risk of sepsis:
Extremes of age, compromised immune system, prolonged hospitalization, disruption in
natural barriers to bacterial injury, malignancies.
Microorganisms: Prior to the introduction of antibiotics in clinical practice, gram-positive
bacteria were the principal organisms causing sepsis. More recently, gram-negative
bacteria and fungal infections have become key pathogens causing severe sepsis and
septic shock.
Pathophysiology:
SIRS results from a dysregulated inflammatory response.
Activation of the complement system leads to generation of bradykinin and nitric oxide
which have been implicated in the induction of hypotension and hyperdynamic shock.
Abnormalities of coagulation and fibrinolysis homeostasis in sepsis
An imbalance of homeostatic mechanisms lead to subclinical coagulopathy and
occasionally disseminated intravascular coagulopathy (DIC) and microvascular
thrombosis causing organ dysfunction and death. Activated protein C acts as an
antithrombotic in the microvasculature, but is decreased in sepsis.
The imbalance among inflammation, coagulation, and fibrinolysis results in widespread
coagulopathy and microvascular thrombosis and suppressed fibrinolysis, ultimately
leading to multiple organ dysfunction and death.
Circulatory pathophysiology of septic shock
The predominant hemodynamic feature of septic shock is arterial vasodilation.
Peripheral circulation during septic shock
An elevation of cardiac output occurs; however, the arterial-mixed venous oxygen
difference usually is narrow, and the blood lactate level is elevated. This is a result of
maldistribution of blood flow and oxygen delivery/extraction.
Diagnostic Tests
CBC
Chemistry - Na, Cl, HCO3, BUN, Cr, lactate, liver tests
Coagulation studies.
Blood and Urine cultures, preferably prior to initiation of antibiotics.
Chest x-ray
Abdominal films, possibly including CT if unable to localize site of infection, especially
if the patient has abdominal complaints.
Lumbar puncture if the patient has meningeal signs or altered mental status.
Treatment
General supportive care: Initial treatment includes support of respiratory and
circulatory function, supplemental oxygen, mechanical ventilation, and volume infusion.
Hemodynamic support of septic shock
Evidence of inadequate tissue perfusion and oxygenation:
MAP < 60 mmHg, or a decrease in MAP of greater than 40 mm Hg.
Elevated blood lactate.
Mixed venous saturation of less than 65%.
Evidence of end-organ damage – acute coronary syndrome, renal dysfunction (decrease
urine output or increase in creatinine), decreased level of consciousness, elevated
transaminases, ileus or malabsorption.
The hemodynamic support in septic shock is provided by restoring the adequate
circulating blood volume, and, if needed, optimizing the perfusion pressure and cardiac
function with vasoactive and inotropic support to improve tissue oxygenation.
Intravascular volume resuscitation
Up to 10 L in six hours. Frequent (2 to 3/hour) boluses of 10 to 20 ml/kg.
Reassess for clinical endpoints frequently
Vasopressor supportive therapy
When proper fluid resuscitation fails to restore hemodynamic stability and tissue
perfusion, initiate therapy with vasopressor agents. Typical agents are: dopamine,
norepinephrine, epinephrine, and phenylephrine.
Empirical antimicrobial therapy
Initiate this therapy early (prior to cultures if obtaining cultures would result in a delay in
administering antibiotics) in patients experiencing septic shock as appropriate antibiotic
therapy has been shown to have a survival benefit when compared to delayed, inadequate
or inappropriate antibiotic therapy, though antibiotics have little effect on the clinical
outcome in the first 24 hours
Surgery may be required for patients with localized foci of infections (abscesses) or
intraabdominal infections.
Recombinant human activated protein C
A recent publication by the Recombinant Human Activated Protein C Worldwide
Evaluation in Severe Sepsis (PROWESS) study group demonstrated that the
administration of recombinant human activated protein C (drotrecogin-alfa, activated)
resulted in lower mortality rates (24.7% versus 30.8%) in the treated group compared to
placebo.
High-dose glucocorticoids: While theoretical and experimental animal evidence exists
for the use of large doses of corticosteroids in those with severe sepsis and septic shock,
all randomized human studies (except 1 from 1976) found that corticosteroids did not
prevent the development of shock, reverse the shock state, or improve the 14-day
mortality rate. However, a study reported in JAMA in 2002 showed that 75% of patients
in the study who remained hypotensive despite adequate fluid resuscitation and
vasopressor therapy were adrenally insufficient and did benefit from hydrocortisone and
fludrocortisone.
Stress-dose glucocorticoids: Recent trials demonstrated positive results of stress-dose
administration of corticosteroids in patients with severe and refractory shock.
Review Question
A 71 year old man with a history of hypertension and chronic bronchitis who continues to
smoke presents with a complaint of increasing shortness of breath. He has felt feverish
and has had an increase in his usual cough, which is now productive of green, blood
tinged sputum. His medications prior to admission were an Albuterol inhaler PRN,
Atrovent inhaler every six hours, and he had increased his prednisone from his usual 5
mg per day to 40 mg per day this morning because, “That’s what his doctor usually does
when he has an exacerbation.” On exam the patient is pale, diaphoretic and appears
anxious. Vitals: P 122, BP 92/42, Temp. 38.2, Resp. 24, O2 Sat. 90% on RA. He
responds appropriately to questions, but is oriented only to person. He has no retractions
and has good air movement. Crackles are heard in the left posterior lung fields.
What intervention will have the most immediate impact on this patient’s mortality?
A) Initiate empirical antibiotics for community acquired pneumonia with a macrolide
and a third generation cephalosporin.
B) Obtain sputum and blood cultures prior to initiation of antibiotics.
C) Obtain a CXR to affirm the cause of the patient’s symptoms are due to pneumonia
rather than an exacerbation of CHF prior to any intervention.
D) Bolus with 1 L of NS immediately, then repeat boluses with 250 to 500 cc of
crystalloid solution until the patient is clinically volume repleted.
E) Administer norepineprhine, initial dose 0.5 mcg/kg/min, titrate to MAP of 60.
Post Module Evaluation
Please place completed evaluation in an interdepartmental mail envelope and address to
Dr. Wendy Gerstein, Department of Medicine, VAMC (111).
1) Topic of module:__________________________
2) On a scale of 1-5, how effective was this module for learning this topic? _________
(1= not effective at all, 5 = extremely effective)
3) Were there any obvious errors, confusing data, or omissions? Please list/comment
below:
________________________________________________________________________
________________________________________________________________________
________________________________________________________________________
________________________________________________________________________
4) Was the attending involved in the teaching of this module? Yes/no (please circle).
5) Please provide any further comments/feedback about this module, or the inpatient
curriculum in general:
6) Please circle one:
Attending
Resident (R2/R3)
Intern
Medical student