Distributive Shock Professor Magdy Amin RIAD Professor of Otolaryngology. Ain shames University Senior Lecturer in Otolaryngology University of Dundee

Distributive Shock

Professor Magdy Amin RIAD

Professor of Otolaryngology. Ain shames University

Senior Lecturer in OtolaryngologyUniversity of Dundee

Background:

• Shock may be defined as a state in which alterations in tissue perfusion result in end-organ 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

Ceftazidime (Ceptaz, Fortaz, Tazicef, Tazidime) -- Third-generation cephalosporin with broad-spectrum 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.

Adult Dose 2 g IV q8h

Pediatric Dose

Not established

Contraindications

Documented hypersensitivity

InteractionsNephrotoxicity may increase with aminoglycosides,

furosemide, and ethacrynic acid; probenecid may increase ceftazidime levels

Pregnancy B - Usually safe but benefits must outweigh the risks.

Precautions 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.


Pediatric Dose Not established

Contraindications Documented hypersensitivity

Drug Name Levofloxacin (Levaquin) -- For infections due to multidrug-resistant gram-negative organisms.

Adult Dose 500 mg IV q24h

Pediatric Dose

Not established

Contraindications


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


Contraindications

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


PrecautionsAdjust 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 Dose2 mg/kg when using multiple daily dosing 5-7 mg/kg/d when once daily dosing used


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)


PrecautionsNarrow 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 NameAmpicillin (Marcillin, Omnipen, Polycillin) -- Bactericidal activity against susceptible organisms. Alternative to amoxicillin when unable to take medication orally.



Contraindications


InteractionsProbenecid and disulfiram elevate ampicillin levels; allopurinol decreases ampicillin effects and has additive effects on ampicillin rash; may decrease effects of oral contraceptives


PrecautionsAdjust 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 Dose2 mg/kg when using multiple daily dosing 5-7 mg/kg/d when once daily dosing used


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)


PrecautionsNarrow 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 NameTobramycin (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 Dose2 mg/kg bid/qid or 5-7 mg/kg IV/IM qd; subsequent dosing is individualized based on renal function


Contraindications


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


PrecautionsAvoid use in renal impairment, preexisting auditory or vestibular impairment, and in patients with neuromuscular disorders; aminoglycosides are associated with nephrotoxicity and ototoxicity

Drug NameAmikacin (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 Dose7.5 mg/kg bid/qid or 15 mg/kg/d qd; individualize subsequent dosing based on renal function


Contraindications


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


PrecautionsNot 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


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


PrecautionsCaution 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


Contraindications

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


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 NameDexamethasone (Decadron) -- For various allergic and inflammatory diseases. Decreases inflammation by suppressing migration of polymorphonuclear leukocytes and reducing capillary permeability.

Adult Dose0.4 mg/kg IV q12h for 48 h, first dose administered with or just before antibiotics


Contraindications Documented hypersensitivity; fungal infection

InteractionsEffects decrease with coadministration of barbiturates, phenytoin, and rifampin; dexamethasone decreases effect of salicylates and vaccines used for immunization


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


Contraindications Documented hypersensitivity; pheochromocytoma; ventricular fibrillation

InteractionsPhenytoin, alpha- and beta-adrenergic blockers, general anesthesia, and MAOIs increase and prolong effects of dopamine


PrecautionsTachycardia 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

Drug Dose Cardiac Output

Blood Pressure

Systemic Vascular Resistance

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 + +/- -

Documents

Distributive Shock Professor Magdy Amin RIAD Professor of Otolaryngology. Ain shames University Senior Lecturer in Otolaryngology University of Dundee