Corticosteroids may be used following fluid intake and treatment with vasoactive drugs if no improvement in lactate levels is seen after the first 6 h. The corticosteroids allow for the vasoactive drugs to be gently withdrawn from the system. It has also been shown that when low or high doses of corticosteroids are given over a long period of time, they reduce mortality rates and shortened the amount of time spent in shock (and thus reduce the time the patient needs to be on vasopressors).
Blood Glycemia Regulation
High blood sugar levels can promote the development of organ failure in extremely ill patients. Thus treatments to control blood sugar may be provided in conjunction with primary sepsis treatment. Glycemia is controlled by regulating nutrition and other blood sugar level influencers. Patients may also be treated with insulin infusion therapy that is both aggressive but maintains glycemia levels at 140 mg/dL. Just as hyperglycemia can be harmful to patients in critical condition, so can hypoglycemia. Low blood sugar increases mortality and can undermine glycemia regulation therapy. More important than preventing high or low blood sugar is to prevent major fluctuations in blood sugar.
In addition to adjunctive and primary therapies, support mechanisms are also needed to maintain the health of patients with sepsis or septic shock. Some of these mechanisms include:
- Mechanical ventilation (in the case of acute respiratory distress syndrome)
- enteral nutrition
- deep venous thrombosis prophylaxis
- renal replacement therapy (in the case of renal failure)
Therapies in Development
Despite the many therapies and management strategies available for sepsis, mortality is still high. Currently, there are many treatments in the pipeline for sepsis and septic shock. These treatments are primarily focused on modulating the inflammatory response to infection by utilizing different regulators such as inflammatory cytokines, cellular receptors, nuclear transcription factors, coagulation activators and apoptosis regulators. Personalized medicine is also being explored. Lipopolysaccharide or LPS contribute to the pathology of sepsis by acting as endotoxins. These endotoxins can be destroyed when bound by low-density lipoproteins (LDL) and high-density lipoproteins (HDL). Studies are currently looking at these and other antiendotoxin therapies (such as anti-CD 14 antibodies and lipid A analogs) to help treat sepsis. Hyperbaric oxygen, or HBO, has also been shown to be a promising method of treating sepsis. Phagocytic leukocytes fight against invading pathogens. Their activity depends on oxygen available to them. HBO increases the survival rate of hosts with aerobic septicemia, a type of blood infection. HBO also reduces production of reactive species such as NO and expression of NOS and eNOS. Fibrates or fenofibrate, a class of amphipathic carboxylic acids, act as antioxidant and anti-inflammatory molecules by activating the peroxisome proliferator-activated receptor alpha activation. Treatment with these chemicals reduced mortality rates by more than 12% in one study. Levosimendan, a calcium detecting therapy with inotropic properties has also been shown to be beneficial in improving the outcomes of patients with sepsis. However, it does not reduce the severity of organ damage or failure or reduce mortality rates. It also may have some side effects such as supraventricular tachyarrhythmia (an unusually fast heartbeat).
Treatments currently being investigated include:
- E5564 (Eritoran)
- TAK 242 (Resatorvid)
- Polymyxin B fiber column
- Plasma or whole blood exchange
- Coupled plasma filtration adsorption (CPFA)
- Recombinant thrombomodulin
- Inhibition of programmed cell death 1 (PD-1) and of its ligand (PD-L1)
- Inhibition of B- and T-lymphocyte attenuator (BTLA)
- Inhibition of cytotoxic T-lymphocyte antigen 4 (CTLA- 4)
Sepsis management team
Because sepsis is such a complex disease that affects many different organs and systems quickly and simultaneously, it is vital that the healthcare team is made up of a variety of professionals in all the systems that could potentially be affected.