Distributive Shock Medication
- Author: Lalit K Kanaparthi, MD; Chief Editor: Michael R Pinsky, MD, CM, FCCP, FCCM more...
Medication Summary
Because initial therapy must be empiric, antimicrobial coverage should be broad, with good penetration to all suspected sites of infection. Other important factors in choosing an agent include history, suspected site of infection, comorbid diseases, and pathogen susceptibility patterns in the hospital and community. Avoid antibiotics recently received by the patient.
Antimicrobial regimens should be tailored once the causative pathogen and its susceptibility are identified, because narrow-spectrum treatment decreases the risk of superinfection with resistant organisms.
The role of corticosteroids as an adjunct treatment for septic shock has been an area of debate. Recommendations from the Surviving Sepsis Campaign (SSC) support giving hydrocortisone only to hypotensive patients who are poorly responsive to fluid resuscitation and vasopressors. Hydrocortisone is the steroid of choice.[59]
The use of systemic vasopressors is indicated in patients with hypotension due to sustained septic shock in whom fluid resuscitation does not reverse hypotension. Systemic vasopressors are used to restore blood flow to pressure-dependent vascular beds (eg, the heart and brain). Either norepinephrine or dopamine should be used as first-line treatment; no evidence suggests the use of one over the other.
Antibiotics
Class Summary
Empiric antimicrobial therapy must be comprehensive and should cover all likely pathogens in the context of the clinical setting.
Ceftazidime (Fortaz, Tazicef)
Ceftazidime is a third-generation cephalosporin with broad-spectrum, gram-negative activity; lower efficacy against gram-positive organisms; and higher efficacy against resistant organisms. It arrests bacterial growth by binding to 1 or more penicillin-binding proteins.
Nafcillin
Nafcillin is the initial therapy for suspected penicillin G–resistant streptococcal or staphylococcal infections. Use parenteral therapy initially in severe infections, and change to oral therapy as the condition warrants. Because of thrombophlebitis, particularly in elderly patients, administer nafcillin parenterally for only a short period (1-2 d); change to the oral route as clinically indicated.
Levofloxacin (Levaquin)
Levofloxacin is used for infections caused by multidrug-resistant, gram-negative organisms.
Ampicillin
Ampicillin has bactericidal activity against susceptible organisms. It serves as an alternative to amoxicillin when the patient is unable to take medication orally. It is rarely used in septic shock.
Clindamycin (Cleocin)
Clindamycin is a lincosamide for the treatment of serious skin and soft-tissue staphylococcal infections. It is also effective against aerobic and anaerobic streptococci (except enterococci). Clindamycin inhibits bacterial growth, possibly by blocking the dissociation of peptidyl transfer ribonucleic acid (tRNA) from ribosomes that cause RNA-dependent protein synthesis to arrest. It also counteracts bacterial toxins.
Gentamicin
Gentamicin is an aminoglycoside antibiotic for gram-negative coverage. It is used in combination with an agent against gram-positive organisms and one that covers anaerobes.
Gentamicin is not the drug of choice (DOC). Consider using it if penicillins or other less-toxic drugs are contraindicated, when it is clinically indicated, and in mixed infections caused by susceptible staphylococci and gram-negative organisms.
Dosing regimens for gentamicin are numerous; adjust the dose based on creatinine clearance (CrCl) and changes in the volume of distribution. It may be administered intravenously or intramuscularly.
Tobramycin (TOBI)
Tobramycin is 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.
Amikacin
Amikacin irreversibly binds to the 30S subunit of bacterial ribosomes. It blocks the recognition step in protein synthesis, causing growth inhibition. Use the patient's ideal body weight (IBW) for the dosage calculation.
Vancomycin
Vancomycin is a potent antibiotic that is directed against gram-positive organisms and is active against Enterococcus species. It is useful in the treatment of septicemia and skin structure infections. Vancomycin is indicated for patients who cannot receive or have failed to respond to penicillins and cephalosporins or who have infections with resistant staphylococci. For abdominal penetrating injuries, vancomycin is combined with an agent that is active against enteric flora and anaerobes.
To avoid toxicity, the current recommendation is to assay vancomycin trough levels after the third dose, drawn 0.5 hour prior to the next dosing. Use creatinine clearance to adjust the dose in patients diagnosed with renal impairment.
Vancomycin is used in conjunction with gentamicin for prophylaxis in patients allergic to penicillin who are undergoing gastrointestinal or genitourinary procedures.
Erythromycin (Erythrocin, E.E.S., Ery-Tab, EryPed)
Erythromycin inhibits bacterial growth, possibly by blocking dissociation of peptidyl tRNA from ribosomes that cause RNA-dependent protein synthesis to arrest. It is used for the treatment of staphylococcal and streptococcal infections.
In children, age, weight, and the severity of infection determine proper dosage. When twice-daily dosing is desired, the half-total daily dose may be taken every 12 hours. For more severe infections, double the dose.
Azithromycin (Zithromax, Zmax)
Azithromycin is used to treat mild to moderate microbial infections.
Corticosteroids
Class Summary
These agents have anti-inflammatory properties and cause profound and varied metabolic effects. Corticosteroids modify the body's immune response to diverse stimuli.
Hydrocortisone (Solu-Cortef, Cortef)
Hydrocortisone is the corticosteroid of choice in shock because of its mineralocorticoid activity and glucocorticoid effects. It may be given to hypotensive patients who are poorly responsive to fluid resuscitation and vasopressors.
Vasopressors
Class Summary
These agents augment coronary and cerebral blood flow present during a state of low blood flow.
Vasopressin (ADH, Pitressin)
Vasopressin has vasopressor and antidiuretic hormone (ADH) activity. It increases water resorption at the distal renal tubular epithelium (ADH effect). It promotes smooth muscle contraction throughout the vascular bed of the renal tubular epithelium (vasopressor effects). Vasoconstriction is also increased in splanchnic, portal, coronary, cerebral, peripheral, pulmonary, and intrahepatic vessels.
Dopamine
Dopamine stimulates adrenergic and dopaminergic receptors. Its hemodynamic effect is dose dependent. Lower doses predominantly stimulate dopaminergic receptors that, in turn, produce renal and mesenteric vasodilation. Cardiac stimulation and renal vasodilation are produced by higher doses.
After initiating therapy, increase the dose by 1-4mcg/kg/min every 10-30 minutes until the optimal response is obtained. More than 50% of patients are maintained satisfactorily on doses of less than 20mcg/kg/min.
Norepinephrine (Levarterenol, Levophed)
Norepinephrine is used in protracted hypotension following adequate fluid replacement. It stimulates beta1- and alpha-adrenergic receptors, which, in turn, increases cardiac muscle contractility and heart rate, as well as vasoconstriction. As a result, it increases systemic blood pressure and cardiac output. Adjust and maintain infusion to stabilize blood pressure (eg, 80-100 mm Hg systolic) sufficiently to perfuse vital organs.
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| Diagnosis | Pulmonary Capillary Wedge Pressure | Cardiac Output |
| Cardiogenic shock* | Increased | Decreased |
| Extracardiac obstructive shock 1. Pericardial tamponade† 2. Pulmonary embolism | Increased Normal or decreased | Decreased Decreased |
| Hypovolemic shock | Decreased | Decreased |
| Distributive shock 1. Septic shock 2. Anaphylactic shock | Normal or decreased Normal or decreased | Increased or normal Increased or normal |
| *In cardiogenic shock due to a mechanical defect, such as mitral regurgitation, forward cardiac output is reduced, although the measured cardiac output may be unreliable. Large V waves are commonly observed in the pulmonary capillary wedge tracing in mitral regurgitation. †The hallmark finding is equalization of right atrial mean, right ventricular end-diastolic, pulmonary artery (PA) end-diastolic, and pulmonary capillary wedge pressures. | ||
| Drug | Dose | Principal Mechanism | Cardiac Output | Blood Pressure | SVR |
| Inotropic agents | |||||
| Dobutamine | 2-20 mcg/kg/min | Beta 1 | ++ | + | + |
| Dopamine (low dose) | 5-10 mcg/kg/min | Beta 1, dopamine | ++ | + | + |
| Epinephrine (low dose) | 0.06-0.20 mcg/kg/min | Beta 1, beta 2 >alpha | ++ | + | + |
| Inotropic agents and vasoconstrictors | |||||
| Dopamine (high dose) | >10 mcg/kg/min | Alpha, beta 1, dopamine | ++ | ++ | + |
| Epinephrine (high dose) | 0.21-0.42 mcg/kg/min | Alpha >beta 1, beta 2 | ++ | ++ | + |
| Norepinephrine | 0.02-0.25 mcg/kg/min | Alpha >beta 1, beta 2 | + | ++ | ++ |
| Vasoconstrictors | |||||
| Phenylephrine | 0.2-2.5 mcg/kg/min | Alpha | + | ++ | ++ |
| Vasopressin | 0.10-0.40 U/min | V1 receptor | + | + | ++ |
| Vasodilators | |||||
| Dopamine (very low dose) | 1-4 mcg/kg/min | Dopamine | +/- | +/- | - |
| Milrinone | 0.4-0.6 mcg/kg/min after loading dose; 50 mcg/kg bolus over 5 min | Phosphodiesterase inhibitor | + | +/- | - |
| Alpha and beta refer to agonist activity at these adrenergic receptor sites. Beta 1-adrenergic effects are inotropic and increase contractility. Beta 2-adrenergic effects are chronotropic.[47] | |||||
| Suspected Source | Recommended Antibiotic Therapy | Alternative Therapy |
| No source evident in a healthy host | Third-generation cephalosporin, eg, ceftriaxone 2 g IV q12h, ceftizoxime, ceftazidime | Nafcillin and aminoglycoside, imipenem, piperacillin/tazobactam |
| No source evident in an immunocompromised host | Ceftazidime 2 g IV q8h plus aminoglycoside | Imipenem or piperacillin/tazobactam plus aminoglycoside |
| No source evident in a user of intravenous drugs | Nafcillin 2 g IV q4h plus aminoglycoside | Vancomycin plus aminoglycoside, ceftazidime, imipenem, or piperacillin/tazobactam |
| Bacterial pneumonia, community acquired | Ceftriaxone 2 g IV q12-24 h plus macrolide | Levofloxacin 750mg IV q24h, cotrimoxazole or imipenem plus macrolide |
| Bacterial pneumonia, hospital acquired | Piperacillin/tazobactam 4.5 g IV q6h plus aminoglycoside, plus levofloxacin 750 mg IV q24h | Imipenem plus aminoglycoside, plus macrolide |
| Urinary tract infection | Ampicillin 2 g IV q4h plus aminoglycoside | Fluoroquinolone or third-generation cephalosporin plus aminoglycoside |
| Mixed aerobic and anaerobic abdominal sepsis, aspiration pneumonia, pelvic infection, and necrotizing cellulitis | Third-generation cephalosporin or ampicillin 2 g IV q4h plus aminoglycoside plus clindamycin 600 mg IV q8h or metronidazole 500 mg IV q6h | Fluoroquinolone plus clindamycin, imipenem, piperacillin/tazobactam |
| Meningitis | Ceftriaxone 2 g IV q12h plus vancomycin | Meropenem plus vancomycin, chloramphenicol plus cotrimoxazole plus vancomycin |
| Cellulitis/erysipelas | Nafcillin 2 g IV q4h | Cefazolin, vancomycin, clindamycin |
| Toxic shock syndrome (TSS) or streptococcal necrotizing fasciitis | Clindamycin 600 mg IV q8h | Cephalosporin, vancomycin, nafcillin |
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