Multiple Organ Dysfunction Syndrome in Sepsis Medication

The proven medical treatments for septic shock are restoration of intravascular volume and broad-spectrum empiric antibiotic coverage. All other medical therapies, though theoretically attractive, have not been shown to reduce morbidity or mortality.

Class Summary

Isotonic crystalloids are the standard for initial volume resuscitation. These fluids expand the intravascular and interstitial fluid spaces. Typically, approximately 30% of administered isotonic fluid remains intravascular; therefore, large quantities may be required to maintain an adequate circulating volume.

Normal saline and lactated Ringer solution

Both normal saline (NS) and lactated Ringer solution (LR) are essentially isotonic and have equivalent volume restorative properties. Whereas some differences exist between the 2 solutions with respect to the metabolic changes observed with administration of large quantities, for practical purposes and in most situations, the differences are clinically irrelevant. No demonstrable difference in hemodynamic effect, morbidity, or mortality exists between resuscitation with NS and resuscitation with LR.

The amounts of intravascular fluid required are related to the degree of vascular endothelial injury and impaired vasomotor tone; thus, not only may very large quantities of fluids be required initially, but continual fluid resuscitation also is often required during the initial days of management.

Class Summary

Colloids are used for resuscitation because they provide an oncotically active substance that expands plasma volume to a greater degree than isotonic crystalloids do while reducing the tendency toward pulmonary and cerebral edema. Approximately 50% of the administered colloid remains intravascular.

Albumin 5% (Albuminar, Buminate, Kedbumin)

Albumin is used for treatment of certain types of shock or impending shock. It is useful for plasma volume expansion and maintenance of cardiac output. A solution of NS and 5% albumin is available for volume resuscitation.

Class Summary

Besides resuscitation fluids, empiric antibiotics that cover the infecting organism and are started early are the only other proven medical treatment for septic shock. Administer all initial antibiotics intravenously (IV) in patients with septic shock.

The necessary coverage is achieved by giving a single broad-spectrum agent or multiple antibiotics. In adults who are not immunocompromised, monotherapy with either an antipseudomonal penicillin or a carbapenem is possible. Combination therapy in adults involves either a third-generation cephalosporin plus anaerobic coverage (clindamycin or metronidazole) or a fluoroquinolone plus clindamycin.

Cefotaxime (Claforan)

Cefotaxime is used for treatment of bloodstream infection (BSI), as well as for treatment of gynecologic infections caused by susceptible organisms. It is a third-generation cephalosporin with enhanced gram-negative coverage, especially of Escherichia coli, Proteus species, and Klebsiella species. It has variable activity against Pseudomonas species.

Ceftriaxone (Rocephin)

Ceftriaxone is used because of the increasing prevalence of penicillinase-producing microorganisms. It inhibits bacterial cell wall synthesis by binding to 1 or more of the penicillin-binding proteins. Bacteria eventually lyse as a consequence of the ongoing activity of cell wall autolytic enzymes while cell wall assembly is arrested.

Cefuroxime (Zinacef, Ceftin)

Cefuroxime is a second-generation cephalosporin that maintains the gram-positive activity of the first-generation cephalosporins and adds activity against E coli, Klebsiella pneumoniae, Proteus mirabilis, Haemophilus influenzae, and Moraxella catarrhalis. The condition of the patient, the severity of the infection, and the susceptibility of the microorganism determine the proper dose and route of administration.

Ticarcillin-clavulanate (Timentin)

Ticarcillin-clavulanate is a combination of an antipseudomonal penicillin with a beta-lactamase inhibitor that provides coverage against most gram-positive organisms (variable coverage against Staphylococcus epidermidis and none against methicillin-resistant Staphylococcus aureus [MRSA]), most gram-negative organisms, and most anaerobes.

Piperacillin-tazobactam (Zosyn)

Piperacillin-tazobactam inhibits the biosynthesis of cell wall mucopeptide and is effective during the stage of active multiplication. It has antipseudomonal activity.

Imipenem-cilastatin (Primaxin)

Imipenem cilastatin is a carbapenem with activity against most gram-positive organisms (except MRSA), gram-negative organisms, and anaerobes. It is used for treatment of polymicrobial infections in which other agents do not have wide-spectrum coverage or are contraindicated because of their potential for toxicity.

Meropenem (Merrem)

Meropenem is a carbapenem that, compared with imipenem, has slightly increased activity against gram-negative organisms and slightly decreased activity against staphylococci and streptococci.

Clindamycin (Cleocin)

Clindamycin is primarily used for its activity against anaerobes. It has some activity against streptococcus and methicillin-sensitive S aureus (MSSA).

Metronidazole (Flagyl)

Metronidazole is an imidazole ring-based antibiotic that is active against various anaerobic bacteria and protozoa. It is usually employed in combination with other antimicrobial agents, except when it is used for Clostridium difficile enterocolitis, in which case monotherapy is appropriate.

Ciprofloxacin (Cipro)

Ciprofloxacin is a fluoroquinolone that inhibits bacterial DNA synthesis and, consequently, growth by inhibiting DNA gyrase and topoisomerases, which are required for replication, transcription, and translation of genetic material. Quinolones have broad activity against gram-positive and gram-negative aerobic organisms. Ciprofloxacin has no activity against anaerobes. Continue treatment for at least 2 days (typically, 7-14 days) after signs and symptoms have disappeared.

Class Summary

Activated protein C analogues exert antithrombotic effects, have indirect profibrinolytic activity, and may have anti-inflammatory effects.

Drotrecogin alfa (Xigris)

October 25, 2011: Withdrawn from worldwide market. Drotrecogin alfa was indicated for reduction of mortality in patients with severe sepsis associated with acute organ dysfunction and at high risk of death.

Drotrecogin alfa is a recombinant form of activated protein C that exerts antithrombotic effects by inhibiting factors Va and VIIIa. It has indirect profibrinolytic activity by inhibiting plasminogen activator inhibitor-1 and limiting formation of activated thrombin-activatable fibrinolysis inhibitor. It may exert anti-inflammatory effects by inhibiting human tumor necrosis factor production by monocytes, blocking leukocyte adhesion to selectins, and limiting thrombin-induced inflammatory responses within microvascular endothelium.

Class Summary

If a patient does not respond to several liters of isotonic crystalloid (usually 4 L or more), or if evidence of volume overload is present, the depressed cardiovascular system can be stimulated by inotropic and vasoconstrictive agents.

Dopamine

Dopamine is used to treat hypotension in fluid-resuscitated patients. It stimulates both adrenergic and dopaminergic receptors. The hemodynamic effect depends on the dose. Lower doses stimulate mainly dopaminergic receptors that produce renal and mesenteric vasodilation in healthy volunteers but probably have no measurable effect in patients who are critically ill. Higher doses produce cardiac stimulation, tachycardia, and vasoconstriction.

Norepinephrine (Levophed)

Norepinephrine, like dopamine, is used to treat hypotension after adequate fluid resuscitation. It stimulates beta1-adrenergic and alpha-adrenergic receptors, which increase arterial tone and cardiac contractility. As a result, systemic blood pressure and coronary blood flow increase with norepinephrine, though myocardial oxygen demand also may increase.

Once a response has been obtained, adjust the infusion rate to maintain a mean arterial pressure greater than 60 mm Hg. Blood pressures below this threshold are insufficient to perfuse vital organs; however, raising pressures much above 70 mm Hg with vasopressors does not further increase tissue blood flow.

Vasopressin (Pitressin)

Vasopressin has vasopressor and antidiuretic hormone (ADH) activity. Although it does not increase blood pressure in healthy subjects, it markedly increases vasomotor tone in patients with septic shock. It also increases water resorption at the distal renal tubular epithelium (ADH effect) and promotes smooth muscle contraction throughout the vascular bed of the renal tubular epithelium (vasopressor effects). Vasoconstriction also is increased in splanchnic, portal, coronary, cerebral, peripheral, pulmonary, and intrahepatic vessels.

Vasopressin is not yet routinely used to treat hypotension in septic shock. The dosage of vasopressin used for hypotension is 10% of that used to treat upper gastrointestinal bleeding from varices.