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Distributive Shock
Professor Magdy Amin RIAD
Professor of Otolaryngology.
Ain shames University
Senior Lecturer in Otolaryngology
University of Dundee
Background:
• Shock may be defined as a state in which
alterations in tissue perfusion result in endorgan dysfunction.
• Untreated or refractory shock leads to
permanent organ damage and, eventually, to
death.
Background:
• Distributive shock is characterized by
hypotension (systolic blood pressure <90
mm Hg) due to a severe reduction in
systemic vascular resistance (SVR), with
normal or elevated cardiac output in most
instances.
Causes of shock
• Septic shock is the most commonly
encountered form of distributive shock.
• Is now the most common cause of
noncardiac death in intensive care units
(ICUs) in the.
Other causes of distributive shock
• systemic inflammatory response syndrome (SIRS)
due to noninfectious inflammatory conditions.
• Toxic shock syndrome (TSS).
• anaphylaxis; drug or toxin reactions.
• Transfusion reaction.
• Addisonian crisis; hepatic insufficiency; and
neurogenic shock due to brain or spinal cord
injury
Pathophysiology:
• Decreased tissue perfusion in distributive
shock results primarily from arterial
hypotension caused by a reduction in SVR.
• In addition, a reduction in effective
circulating plasma volume often occurs due
to a decrease in venous tone and subsequent
pooling of blood in venous capacitance
vessels.
Pathophysiology:
• Loss of intravascular volume into the interstitium
due to increased capillary permeability also
occurs.
• Finally, primary myocardial dysfunction often is
present as manifested by ventricular dilatation,
decreased ejection fraction (despite normal stroke
volume and cardiac output), and depressed
ventricular function curves
Pathophysiology of septic shock
and SIRS
• The hemodynamic derangements observed
in septic shock and SIRS are due to a
complicated cascade of inflammatory
mediators released in response to infection,
inflammation, or tissue injury.
Pathophysiology of septic shock
and SIRS
• Tumor necrosis factor-alpha (TNF-alpha),
interleukin (IL)-1b, and IL-6 act
synergistically with other cytokines and
phospholipid-derived mediators to produce
the complex alterations in vascular and
myocardial function, which leads to
maldistribution of blood flow
Pathophysiology: In anaphylaxis
• In anaphylaxis, decreased SVR is due
primarily to massive histamine release from
mast cells after activation by antigen-bound
immunoglobulin E (IgE), as well as
increased synthesis and release of
prostaglandins.
Mortality/Morbidity:
• The overall death rate after development of septic shock is
35-50%. Recent data suggest that mortality due to septic
shock has decreased slightly over the past decade.
• Higher mortality rates have been associated with advanced
age, the finding of positive blood cultures, infection with
antibiotic-resistant organisms such as Pseudomonas
aeruginosa, elevated serum lactate levels, impaired
immune function, and poor functional status prior to the
onset of sepsis.
History:
• Patients with shock frequently present with
dyspnea or respiratory distress, mental status
changes, and obtundation.
• Patients with septic shock or SIRS may have prior
complaints suggesting infection or inflammation
of the respiratory tract, urinary tract, or abdominal
cavity.
• Septic shock occurs frequently in hospitalized
patients with risk factors, such as indwelling
catheters or venous access devices, recent surgery,
or immunosuppressive therapy.
History:
• Patients with anaphylaxis commonly have
recent iatrogenic (drug) or accidental (ie,
bee sting) exposure to an allergen and
coexisting respiratory complaints (wheezing
and dyspnea) and/or pruritus.
History:
Shock due to adrenal insufficiency may be observed in
patients with chronic adrenal insufficiency and recent
physiologic stress or in new-onset adrenal insufficiency.
– Long-term treatment with corticosteroids may result in inadequate
response of the adrenal axis to stress, such as infection, surgery, or
trauma, and subsequent onset or worsening of shock.
– Adrenal insufficiency also occurs in as many as 20% of patients with
AIDS.
– Adrenal insufficiency as a cause of shock should be considered in any
patient with hypotension who lacks signs of infection, cardiovascular
disease, or hypovolemia.
History:
• Streptococcal TSS is associated with recent
soft tissue injury, surgery, pharyngitis, and
nonsteroidal anti-inflammatory drug
(NSAID) use. Patients often have a history
of influenzalike illness (fever, arthralgias,
myalgias).
History:
• Staphylococcal TSS still is observed most
commonly in women who are menstruating,
but it also is associated with cutaneous
infections, postpartum and cesarean section
wound infections, and focal staphylococcal
infections, such as abscess, empyema,
pneumonia, and osteomyelitis.
Physical examination:
• Cardinal features of distributive shock include the
following:
– Hypotension - With systolic blood pressure less than 90
mm Hg or a reduction of 40 mm Hg from baseline
– Heart rate - Greater than 90 beats per minute
– Respiratory rate - Greater than 20 breaths per minute
– Extremities - Frequently are warm with bounding
pulses and increased pulse pressure (systolic minus
diastolic blood pressure)
Septic shock
– The most common sites of infection in
decreasing order are the chest, the abdomen,
and the genitourinary tract.
– When bacteria are present, approximately 70%
of infections are due to gram-negative bacteria
(Enterobacteriaceae, P aeruginosa) and 30%
are caused by gram-positive bacteria
(Streptococcus pneumoniae, Staphylococcus
aureus, Enterococcus species).
Toxic shock syndrome
• High fever
• Diffuse rash with desquamation on the palms and
soles over subsequent 1-2 weeks
• Hypotension (may be orthostatic) and evidence of
involvement of 3 other organ systems
• Streptococcal TSS more frequently presents with
focal soft tissue inflammation and less commonly
is associated with diffuse rash.
• Streptococcus pyogenes (group A Streptococcus)
• S aureus
Systemic inflammatory response
syndrome
–
–
–
–
–
Infection
Surgery
Trauma
Pancreatitis
Fulminant hepatic failure
Anaphylaxis
•
•
•
•
Respiratory distress
Wheezing
Urticarial rash
Angioedema
Lab Studies:
• All patients with evidence of shock should have the
following studies performed:
–
–
–
–
–
–
–
–
–
–
CBC with differential
Arterial blood gas
Serum lactate if metabolic acidosis or elevated anion gap is present
Electrolytes
BUN
Creatinine (CR)
Glucose
Urinalysis
Blood cultures
Urine cultures
Disseminated intravascular
coagulation (DIC)
• All patients with suspected disseminated
intravascular coagulation (DIC) should have
the following studies performed:
• Obtain PT, active partial thromboplastin
time (aPTT), fibrin split products, D-dimer
assay, fibrinogen level, and platelet count.
Imaging Studies:
• All patients should have a chest x-ray performed. The
chest is the most common site of infection causing septic
shock.
• Flat and upright abdominal radiographs may be omitted if
the abdomen is completely benign or if an obvious source
of extraabdominal sepsis noted.
• In suspected cases of cholecystitis or pancreatitis,
abdominal ultrasound is most useful to assess for
cholelithiasis, biliary dilatation, and fluid collections
around the gallbladder or the head of the pancreas.
• Consider abdominal CT scan with oral and/or intravenous
contrast for other abdominal sources for sepsis
Other Tests:
• ECG should be performed to examine for
evidence of underlying cardiac pathology
(left ventricular hypertrophy, cor pulmonale,
low voltage, bundle branch block) or acute
changes of ischemia or pericarditis
Treatment
• Nearly all patients with shock should be
admitted to an ICU.
• Vital signs and fluid intake and output
should be measured and charted on an
hourly basis.
• Adequate intravenous access should be
obtained.
Treatment
• A central venous access device should be
considered if vasoactive drug support is required.
• Most patients should have an indwelling urinary
catheter placed.
• All patients should be treated prophylactically
against thromboembolic disease, gastric stress
ulceration, and pressure ulcers of the skin.
Goals of treatment
• The 2 primary goals of treatment in patients
with shock are to reverse the initiating cause
of shock (e.g.treat infection) and to stabilize
the patient hemodynamically.
• The initial resuscitation of the patient with
shock should be accomplished within the
first hour of treatment.
Treatment
• Oxygen should be administered immediately by mask.
• In patients with altered mental status, respiratory distress,
or severe hypotension, elective endotracheal intubation and
mechanical ventilation should be considered strongly.
• This avoids emergency intubation in the event of
subsequent respiratory arrest.
• Mechanical ventilation also can aid in hemodynamic
stabilization by decreasing the demands posed by the
respiratory muscles on the circulation (as much as 40% of
the cardiac output during respiratory distress).
Treatment
• In all patients with suspected sepsis, empiric
antibiotic therapy should be initiated immediately.
• Patients who receive prompt effective
antimicrobial therapy are more likely to survive
than those whose antibiotic therapy is delayed.
• Because initial therapy necessarily must be
empiric, antimicrobial coverage should be broad,
though tailoring of therapy based on suspected site
of infection is appropriate.
Initial hemodynamic support
• Initial hemodynamic support should be in
the form of fluid resuscitation.
• Crystalloid fluids, such as 0.9% NaCl or
lactated Ringers solution, should be infused
rapidly in 250- to 500-cc boluses, with
frequent reassessment of blood pressure,
extremities, skin turgor, and urine output to
determine response to therapy.
Initial hemodynamic support
• A mean arterial pressure of 60 mm Hg or
systolic blood pressure of 90-100 mm Hg
should be the usual hemodynamic goal.
• Little evidence exists to support the use of
colloids, such as albumin, in most instances.
• If anemia is present, packed red blood cells
can be administered to achieve a
hemoglobin concentration of 8-10 g/dL
If the blood pressure fails to
improve:
• If the blood pressure fails to improve after 2-3 L of rapid
crystalloid infusion, vasoactive drug therapy should be
initiated with dopamine.
• If an adequate hemodynamic response is not achieved with
dopamine infusion rates of 15-20 mg/kg/min or if
excessive tachycardia or tachyarrhythmias develop,
norepinephrine or phenylephrine may be added to or
substituted for dopamine.
• Dobutamine may be added to the therapeutic regimen
when cardiac output is low, recognizing that this drug acts
primarily as a positive inotropic agent and may further
decrease SVR.
anaphylaxis
• If anaphylaxis is suspected, 0.2-0.5 mL of
1:1000 epinephrine should be administered
immediately subcutaneously, with repeated
doses every 20 minutes as needed.
• Epinephrine can be administered by
continuous infusion of 30-60 mL/h of
1:10,000 dilution in severe reactions.
anaphylaxis
• If the agent was administered by injection, a
tourniquet may be applied to the extremity to slow
absorption and 0.2 mL of 1:1000 epinephrine can
be injected at the site.
• Diphenhydramine 50-80 mg IM or IV may be
administered for urticaria or angioedema.
• Inhaled bronchodilators or IV aminophylline can
be administered for bronchospasm.
Adrenal insufficiency
• If adrenal insufficiency is suspected,
hydrocortisone should be administered IV at
an initial dose of 125 mg every 6-8 hours.
• Dexamethasone may be administered
immediately at 10 mg IV without interfering
with subsequent measurements of serum
cortisol levels
Drug Name
Adult Dose
Pediatric
Dose
Contraindic
ations
Ceftazidime (Ceptaz, Fortaz, Tazicef, Tazidime) -Third-generation cephalosporin with broadspectrum gram-negative activity, lower efficacy
against gram-positive organisms, and higher
efficacy against resistant organisms. Arrests
bacterial growth by binding to one or more
penicillin binding proteins.
2 g IV q8h
Not established
Documented hypersensitivity
Interactions
Nephrotoxicity may increase with aminoglycosides,
furosemide, and ethacrynic acid; probenecid may
increase ceftazidime levels
Pregnancy
Precautions
B - Usually safe but benefits must outweigh the risks.
Adjust dose in renal impairment
Drug Name
Nafcillin (Nafcil, Unipen) -- Initial therapy
for suspected penicillin G–resistant
streptococcal or staphylococcal infections.
Use parenteral therapy initially in severe
infections. Change to oral therapy as
condition warrants. Due to thrombophlebitis,
particularly in elderly patients, administer
parenterally only for short term (1-2 d);
change to oral route as clinically indicated.
Adult Dose
2 g IV q4h
Pediatric Dose
Not established
Contraindications
Documented hypersensitivity
Drug Name
Levofloxacin (Levaquin) -- For infections due to
multidrug-resistant gram-negative organisms.
Adult Dose
Pediatric
Dose
500 mg IV q24h
Not established
Contraindica
tions
Documented hypersensitivity
Interactions
Antacids, iron salts, and zinc salts may reduce serum levels; administer
antacids 2-4 h before or after taking fluoroquinolones; cimetidine may
interfere with metabolism of fluoroquinolones; levofloxacin reduces
therapeutic effects of phenytoin; probenecid may increase levofloxacin
serum concentrations; may increase toxicity of theophylline, caffeine,
cyclosporine, and digoxin (monitor digoxin levels); may increase effects of
anticoagulants (monitor PT)
Pregnancy
C - Safety for use during pregnancy has not been established.
Precautions
In prolonged therapy, perform periodic evaluations of organ system
functions (eg, renal, hepatic, hematopoietic); adjust dose in renal function
impairment; superinfections may occur with prolonged or repeated
antibiotic therapy
Drug Name
Clindamycin (Cleocin) -- Lincosamide for treatment of serious skin
and soft tissue staphylococcal infections. Also effective against
aerobic and anaerobic streptococci (except enterococci). Inhibits
bacterial growth, possibly by blocking dissociation of peptidyl
tRNA from ribosomes causing RNA-dependent protein synthesis to
arrest.
Adult Dose
600 mg IV q8h
Pediatric Dose
Not established
Contraindicatio
ns
Documented hypersensitivity; regional enteritis; ulcerative colitis;
hepatic impairment; antibiotic-associated colitis
Interactions
Increases duration of neuromuscular blockade induced by
tubocurarine and pancuronium; erythromycin may antagonize
effects of clindamycin; antidiarrheals may delay absorption of
clindamycin
Pregnancy
B - Usually safe but benefits must outweigh the risks.
Precautions
Adjust dose in severe hepatic dysfunction; no adjustment necessary
in renal insufficiency; associated with severe and possibly fatal
colitis
Drug Name
Gentamicin (Garamycin, Gentacidin) -- Aminoglycoside antibiotic for gram-negative
coverage. Used in combination with an agent against gram-positive organisms and
one that covers anaerobes.
Not the DOC. Consider if penicillins or other less toxic drugs are contraindicated,
when clinically indicated, and in mixed infections caused by susceptible
staphylococci and gram-negative organisms.
Dosing regimens are numerous; adjust dose based on CrCl and changes in volume of
distribution. May be administered IV/IM.
Adult Dose
2 mg/kg when using multiple daily dosing
5-7 mg/kg/d when once daily dosing used
Pediatric Dose
Not established
Contraindications
Documented hypersensitivity; non–dialysis-dependent renal insufficiency
Interactions
Coadministration with other aminoglycosides, cephalosporins, penicillins, and
amphotericin B may increase nephrotoxicity; aminoglycosides enhance effects of
neuromuscular blocking agents, thus prolonged respiratory depression may occur;
coadministration with loop diuretics may increase auditory toxicity of
aminoglycosides; possible irreversible hearing loss of varying degrees may occur
(monitor regularly)
Pregnancy
C - Safety for use during pregnancy has not been established.
Precautions
Narrow therapeutic index (not intended for long-term therapy); caution in renal
failure (not on dialysis), myasthenia gravis, hypocalcemia, and conditions that
depress neuromuscular transmission; adjust dose in renal impairment
Drug Name
Ampicillin (Marcillin, Omnipen, Polycillin) -- Bactericidal activity
against susceptible organisms. Alternative to amoxicillin when
unable to take medication orally.
Adult Dose
2 g IV q4h
Pediatric Dose
Not established
Contraindicatio
ns
Documented hypersensitivity
Interactions
Probenecid and disulfiram elevate ampicillin levels; allopurinol
decreases ampicillin effects and has additive effects on ampicillin
rash; may decrease effects of oral contraceptives
Pregnancy
B - Usually safe but benefits must outweigh the risks.
Precautions
Adjust dose in renal failure; evaluate rash and differentiate from
hypersensitivity reaction
Drug Name
Gentamicin (Garamycin, Gentacidin) -- Aminoglycoside antibiotic for gram-negative
coverage. Used in combination with an agent against gram-positive organisms and
one that covers anaerobes.
Not the DOC. Consider if penicillins or other less toxic drugs are contraindicated,
when clinically indicated, and in mixed infections caused by susceptible
staphylococci and gram-negative organisms.
Dosing regimens are numerous; adjust dose based on CrCl and changes in volume of
distribution. May be administered IV/IM.
Adult Dose
2 mg/kg when using multiple daily dosing
5-7 mg/kg/d when once daily dosing used
Pediatric Dose
Not established
Contraindications
Documented hypersensitivity; non–dialysis-dependent renal insufficiency
Interactions
Coadministration with other aminoglycosides, cephalosporins, penicillins, and
amphotericin B may increase nephrotoxicity; aminoglycosides enhance effects of
neuromuscular blocking agents, thus prolonged respiratory depression may occur;
coadministration with loop diuretics may increase auditory toxicity of
aminoglycosides; possible irreversible hearing loss of varying degrees may occur
(monitor regularly)
Pregnancy
C - Safety for use during pregnancy has not been established.
Precautions
Narrow therapeutic index (not intended for long-term therapy); caution in renal
failure (not on dialysis), myasthenia gravis, hypocalcemia, and conditions that
depress neuromuscular transmission; adjust dose in renal impairment
Drug Name
Tobramycin (Nebcin) -- Indicated in the treatment of staphylococcal
infections when penicillin or potentially less toxic drugs are
contraindicated and when bacterial susceptibility and clinical
judgment justifies its use.
Adult Dose
2 mg/kg bid/qid or 5-7 mg/kg IV/IM qd; subsequent dosing is
individualized based on renal function
Pediatric Dose
Not established
Contraindicatio
ns
Documented hypersensitivity
Interactions
Increases effects of neuromuscular blockers and potentiates effect of
extended-spectrum penicillins; concurrent administration with
amphotericin B, cephalosporins, and loop diuretics increases risk of
nephrotoxicity
Pregnancy
B - Usually safe but benefits must outweigh the risks.
Precautions
Avoid use in renal impairment, preexisting auditory or vestibular
impairment, and in patients with neuromuscular disorders;
aminoglycosides are associated with nephrotoxicity and ototoxicity
Drug Name
Amikacin (Amikin) -- Irreversibly binds to 30S subunit of bacterial
ribosomes; blocks recognition step in protein synthesis; causes
growth inhibition. Use the patient's IBW for dosage calculation.
Adult Dose
7.5 mg/kg bid/qid or 15 mg/kg/d qd; individualize subsequent
dosing based on renal function
Pediatric Dose
Not established
Contraindicatio
ns
Documented hypersensitivity
Interactions
Coadministration with other aminoglycosides, penicillins,
cephalosporins, and amphotericin B increases nephrotoxicity;
enhances effects of neuromuscular blocking agents; causes
respiratory depression; irreversible hearing loss may occur with
coadministration of loop diuretics
Pregnancy
C - Safety for use during pregnancy has not been established.
Precautions
Not intended for long-term therapy; caution in patients with renal
failure (not on dialysis), hypocalcemia, myasthenia gravis, and
conditions that depress neuromuscular transmission
Drug Name
Erythromycin (Erythrocin, Eryc, E-Mycin) -- Inhibits bacterial growth,
possibly by blocking dissociation of peptidyl tRNA from ribosomes causing
RNA-dependent protein synthesis to arrest. For treatment of staphylococcal
and streptococcal infections.
In children, age, weight, and severity of infection determine proper dosage.
When bid dosing is desired, half-total daily dose may be taken q12h. For
more severe infections, double the dose.
Adult Dose
15 mg/kg IV q6h, up to 4 g/d
Pediatric Dose
Not established
Contraindications Documented hypersensitivity; hepatic impairment
Interactions
Coadministration may increase toxicity of theophylline, digoxin,
carbamazepine, and cyclosporine; may potentiate anticoagulant effects of
warfarin; coadministration with lovastatin and simvastatin increases risk of
rhabdomyolysis
Pregnancy
B - Usually safe but benefits must outweigh the risks.
Precautions
Caution in liver disease; estolate formulation may cause cholestatic
jaundice; GI adverse effects are common (administer doses pc); discontinue
use if nausea, vomiting, malaise, abdominal colic, or fever occur
Drug Name
Azithromycin (Zithromax) -- Treats mild-to-moderate microbial
infections
Adult Dose
500 mg IV qd
Pediatric Dose
Not established
Contraindicatio
ns
Documented hypersensitivity; hepatic impairment; do not
administer with pimozide
Interactions
May increase toxicity of theophylline, warfarin, and digoxin; effects
are reduced with coadministration of aluminum and/or magnesium
antacids; nephrotoxicity and neurotoxicity may occur when
coadministered with cyclosporine
Pregnancy
B - Usually safe but benefits must outweigh the risks.
Precautions
Site reactions can occur with IV route; bacterial or fungal
overgrowth may result with prolonged antibiotic use; may increase
hepatic enzymes and cholestatic jaundice; caution in patients with
impaired hepatic function, prolonged QT intervals, or pneumonia;
caution in hospitalized, geriatric, or debilitated patients
Drug Name
Dexamethasone (Decadron) -- For various allergic and inflammatory
diseases. Decreases inflammation by suppressing migration of
polymorphonuclear leukocytes and reducing capillary permeability.
Adult Dose
0.4 mg/kg IV q12h for 48 h, first dose administered with or just before
antibiotics
Pediatric Dose
Not established
Contraindications Documented hypersensitivity; fungal infection
Interactions
Effects decrease with coadministration of barbiturates, phenytoin, and
rifampin; dexamethasone decreases effect of salicylates and vaccines used
for immunization
Pregnancy
C - Safety for use during pregnancy has not been established.
Precautions
Increases risk of multiple complications, including severe infections;
monitor adrenal insufficiency when tapering drug; abrupt discontinuation of
glucocorticoids may cause adrenal crisis; hyperglycemia, edema,
osteonecrosis, myopathy, peptic ulcer disease, hypokalemia, osteoporosis,
euphoria, psychosis, myasthenia gravis, growth suppression, and infections
are possible complications of glucocorticoid use
Drug Name
Dopamine (Intropin) -- Stimulates both adrenergic and dopaminergic receptors. Hemodynamic effect is
dependent on the dose. Lower doses predominantly stimulate dopaminergic receptors that, in turn, produce renal
and mesenteric vasodilation. Cardiac stimulation and renal vasodilation produced by higher doses.
After initiating therapy, increase dose by 1-4 mcg/kg/min q10-30min until optimal response is obtained. More
than 50% of patients are maintained satisfactorily on doses less than 20 mcg/kg/min.
Adult Dose
>10 mcg/kg/min, effects similar to norepinephrine
Pediatric Dose
Not established
Contraindications
Documented hypersensitivity; pheochromocytoma; ventricular fibrillation
Interactions
Phenytoin, alpha- and beta-adrenergic blockers, general anesthesia, and MAOIs increase and prolong effects of
dopamine
Pregnancy
C - Safety for use during pregnancy has not been established.
Precautions
Tachycardia may limit use; phenytoin, alpha- and beta-adrenergic blockers, general anesthesia, and MAOIs
increase and prolong effects of dopamine
Vasoactive Drugs in Sepsis and Usual Hemodynamic Responses
Cardiac
Output
Blood
Pressure
Systemic
Vascular
Resistance
Drug
Dose
Dopamine*
2.5-20 mcg/kg/min
+
+
+
Norepinephrine†
0.05-2 mcg/kg/min
+
++
++
Epinephrine
0.05-2 mcg/kg/min
++
++
+
Phenylephrine
2-10 mcg/kg/min
-
++
++
Dobutamine‡
2.5-10 mcg/kg/min
+
+/-
-