A prospective treatment for sepsis

Abstract

The present paper proposes a prospective auxiliary treatment for sepsis. There exists no record in the published media on the subject. As an auxiliary therapy, efficacious extracorporeal removal of sepsis-causing bacterial antigens and their toxins (BATs) from the blood of septic patients is discussed. The principal component to this approach is a bacterial polyvalent antibody-column (BPVAC), which selectively traps wide spectrum of BATs from blood in an extracorporeal circuit, and detoxified blood returns back to the patient's body. BPVAC treatment would be a device of targeted medicine. Detoxification is performed under supervision of trained personnel using simple blood-circulating machines in which blood circulates from the patient to BPVAC and back to the patient aseptically. BPVACs' reactive sites consist of carbon nanotubes on which a vast spectra of polyvalent BATs-antibodies are bond to. The devise acts as a biological filter that selectively immobilizes harmful BATs from intoxicated blood; however, no dialysis is involved. For effective neutralization, BPVAC provides large contact surface area with blood. BPVAC approach would have advantages of: 1) urgent neutralization of notorious BATs from blood of septic patients; 2) applicability in parallel with conventional treatments; 3) potential to minimize side effects of the malady; 4) applicability for a vast range of BATs; 5) potential to eliminate contact of BATs with internal tissues and organs; 6) tolerability by patients sensitive to antiserum injections; 7) capability for universal application; 8) affectivity when antibiotic-resistant bacteria are involved and the physician has no or limited access to appropriate antibiotics; and 10) being a single-use, disposable, and stand-alone device. Before using it for clinical trials in human beings, it should pass animal evaluations accurately; however, research works should optimize its implementation in human beings. For optimization, it needs appropriate investments, collaboration of scientists in many fields of research, and development through several interdisciplinary sciences such as medical engineering, nanotechnology, immunology, biochemistry, emergency medicine, internal, and infectious diseases.

Keywords: antibiotic; blood; detoxification; infection; polyvalent antibody; targeted medicine.

Figure 1

Schematic diagram of proposed setup for prospective auxiliary treatment of sepses. Notes: It uses BPVAC for removing BATs from the blood of septic patients. BPVAC would work aseptically with the aid of a blood pump in a closed circuit. Main features of the treatment would include (A) hand of septic patient, (B) blood removed from artery, (C) arterial pressure monitor, (D) inflow sampling to detect BATs titer before processing, (E) heparin pump (to prevent clotting), (F) peristaltic blood pump, (G) pressure monitor indicating outflow pressure from the blood pump, and (H) BPVAC, the central component of the treatment, designed to trap and immobilize BATs from infected blood. BATs would adhere to BATs-antibodies, and hence, would be trapped inside the column. (I) pressure monitor indicates outflow pressure from BPVAC, (J) air detector and air trap, (K) outflow sampling to monitor BATs titer by appropriate serological tests, and (L) detoxified blood returns to the vein. All tubing and BPVAC would be applied aseptically; however, they are single-use and would be properly disposed of after treatment. Abbreviations: BPVAC, bacterial polyvalent antibody-column; BATs, bacterial antigens and their toxins.

Figure 2

Prospective structural components of a BPVAC. Notes: BPVAC traps and withdraws BATs in an extracorporeal manner from the blood of septic patients with the help of a blood-circulating machine. (A) Dissected BPVAC, consisting of (a) inlet (intoxicated blood from septic patient enters the column by the help of blood-circulating machine), (b) outlet (detoxified blood leaves the column to return back to the patient), (c) column cylinder, (d) MAPs, and (e) center axis (stacks MAPs in place). (B) A MAP (manufactured from biocompatible organic polymers consisting of an extensive lattice); it bears center spacer (f) and lateral spacers (g) (to keep the MAPs apart). Lattice frame is composed of subunits. (C) A lattice subunit (h). (C′) Cross-section of a lattice subunit bearing millions of nano carbon-rods (i) on its surface. (D) Surface topology of a nano carbon-rod (antibody–antigen reaction platform). (D′) Cross-section of a nano carbon-rod harboring antibody conjugated moieties (j). (E) Antibodies conjugated to supporting moieties. (E′) Monovalent antibodies (k) adhered to moieties. (F) BATs (l) trapped to their antibodies and removed from the blood. Detoxified blood returns back to the patient. Abbreviations: BPVAC, bacterial polyvalent antibody-column; BATs, bacterial antigens and their toxins; MAPs, monovalent antibody plates.