Intraabdominal Lavage of Hypochlorous Acid

A New Paradigm for the Septic and Open Abdomen

Luis G Fernández, MD, KHS, KCOEG, FACS, FASAS, FCCP, FCCM, FICS; Marc R. Matthews, MD, FACS; Lawton Seal, MS, PhD

Disclosures

Wounds. 2020;32(4):107-114. 

In This Article

Discussion

Cutaneous wounds have plagued mankind for thousands of years, and the search for methods to combat infectious pathogens has been met with limited success. Nonetheless, the role of HOCl during the human acute inflammatory response has been well-documented.[2,3] Innate immunity, that which the human infant is typically born with, and acquired immunity both involve cells (eg, neutrophils) that can identify foreign pathogens by chemotaxis.[2] This results in phagocytosis of the prokaryotic pathogen. Following the attachment of the eukaryotic neutrophil membrane to the microbe's glycocalyx (a polysaccharide capsule), the prokaryotic microbe is engulfed and phagocytized into the intracellular phagosome.[3] The bacteria then are bathed in HOCl, destroying the bacteria's cell wall and ability to survive; it is the bacterial cell wall that protects the organism from the environment. Due to the aforementioned reaction, bacterial DNA is exposed, and its synthesis is inhibited by the effects of HOCl. Due to the disruption of DNA synthesis, bacteria cannot duplicate and will rapidly die. Without the ability to produce daughter cells, the bacterial colony cannot be sustained.[2,3]

In addition to activity against prokaryotic organisms, HOCl has demonstrated excellent activity against biofilm, which occurs when prokaryotes form a colony and develop a thin, slime-like film that allows for adherence to any surface.[4–7] Sakarya et al[8] demonstrated dose-related disruption and killing of biofilm-producing microorganisms at HOCl dilutions ranging from 1:32 to 1:16. The authors[8] concluded that HOCl not only penetrated the biofilm but actively killed the microorganisms within the biofilm. The current available data[4–15] confirm the bactericidal and sporicidal activity of HOCl at a 6-log10 challenge; HOCl killed no less than 999 990 of the bacteria in 15 seconds out of a 10[6] viable bacterial load. This means 10 or less of the 1 million microorganisms were alive after a 15-second exposure to HOCl. Furthermore, the rapid (within 15 seconds) sporicidal activity of the HOCl molecule produced less than 1000 Clostridioides difficile spores remaining from the initial 100 000-spore challenge.[4–15] The Table illustrates the large and critical antimicrobial range of HOCl, including a wide range of microorganisms, from gram-positive and gram-negative bacteria to yeast and bacterial endospores, that were completely eliminated with HOCl utilization.[7–15]

Hypochlorous acid has been shown to be an effective agent in reducing bacterial counts in open wounds utilizing ultrasound-enabled wound debridement at the time of definitive closure, the saline-irrigated wounds had bacterial counts return back to 10,[5] whereas the HOCl-irrigated wounds remained at 10[2] counts or fewer.[16] Also, more than 80% of patients in the saline group had postoperative closure failure, compared with 25% of patients in the HOCl group.[16] It is important to note that some HOCl solutions are formulated to remain within a pH range similar to intact skin, while others deliver a solution with a pH that is hostile to the epidermal cell layers and has a potential to induce epidermal cytotoxicity. Therefore, it can take twice as long for hypochlorite solutions to kill when pH increases from 6 to 8.[4–20] Studies[4–20] have demonstrated that lowering pH from 9 to 4.4 was not only effective against vegetative cells but bacterial endospores as well.

The septic abdomen is a life-threatening condition that requires immediate surgical intervention after hollow viscus leakage that has led to life-threatening peritonitis and sepsis. Management of the septic abdomen and the continued release of pro-inflammatory mediators (usually requiring that the abdomen be left open) requires rapid identification and surgical correction of the underlying intraabdominal process, administration of systemic antibiotics, IV resuscitation, and intensive supportive therapy with monitoring in the SICU. Early control of the septic source is mandatory in order to diminish the risk of subsequent multiple organ system failure and is most often achieved by operative means. Patient survival is contingent upon source control, with clearance of all residual infected intraabdominal collections at the index operation and resolution of the underlying sepsis.[21–25] Operative management remains to be the fundamental tool used to control the infectious source, and management of the OA has rapidly evolved over the last several decades, with lessons learned from more recent combat and civilian surgical experiences.[26] Clinical outcomes and decreased mortality in OA cases are largely due to the improved understanding of the underlying pathophysiology that affects patients with an OA, a broader adoption of the concept of DCS, and the use of TAC in this patient population.[26–29] The more prevalent use of OA techniques has generated an increased demand for improved TAC methods in protecting the viscera and fascia during this initial phase of surgical treatment.[30–38]

Negative pressure wound therapy is arguably the best OA management system utilized in the management of patients with an OA when the intestinal contents and other intraperitoneal organs are exposed.[25,29,34,36–47] Due to its ease of application and preservation of fascial tissue, the TAC system used herein has become the most commonly used NPWT technique for TAC in the patient with an OA.[25,29,34,36–47] Negative pressure wound therapy with instillation (also referred to as 2-way therapy) appears to offer superior results in enhanced wound healing in vivo.[44] Some reports[50,51] in the literature suggest instillation of a topical solution not only allows improved removal of wound debris but removes proinflammatory cytokines that may be detrimental to wound healing. In addition, wounds treated with NPWTi-d (V.A.C. VERAFLO Therapy; KCI) utilizing saline as the irrigant and a specialized reticulated open cell foam dressing (V.A.C. VERAFLO CLEANSE CHOICE Dressing; KCI) have increased granulation tissue formation compared with a standard NPWT dressing without irrigation (V.A.C. GRANUFOAM Dressing; KCI) after 7 days of therapy. This form of therapy has been successfully adapted to the abdominal cavity.[50,51]

Several clinical studies[52–64] of wounds in the skin envelope have shown positive results related to better proinflammatory source control, reduction of organ tissue edema, improved microcirculation, and maintenance of a more favorable local wound environment. Kubiak et al[45] suggested intraabdominal NPWT is superior in the reduction of cytokines in the abdominal fluid, thereby assisting in attenuating the systemic inflammatory response in patients receiving this form of therapy. Instillation into the peritoneal cavity, combined with intraabdominal NPWT, has been described with promising clinical success. Sibaja et al[51] described intraabdominal NPWT in 48 patients using 0.9 normal saline and found improved morbidity and mortality, as compared with the standard TAC system. D'Hondt et al[50] described an earlier and similar experience with the use of intraabdominal NPWT to treat abdominal sepsis secondary to a laparostomy after traditional management had failed. Recently, Matthews et al[65] utilized intraabdominal NPWT with instillation of HOCl in a cyclical fashion and after 72 hours noted the purulence and fibrin biofilm were significantly improved to near resolution, with no adverse events noted.

It is often stated that everything old is new again. This is true in the use of intraabdominal HOCl lavage. During World War I and the pre-antibiotic era, from 1915 to 1916, Bates and Fraser[66] studied intraabdominal HOCl placement in injured allied troops. The British military surgeons were desperately searching for ways to rid open wounds and body cavities of harmful prokaryotic pathogens and therefore used HOCl.[66] Smith et al[67] originally described and supported HOCl utilization in civilian wounds and septicemia, including the treatment for puerperal fever in women who were considered terminal by their treating physicians. Further, Bates and Fraser described[66] its use as a lavage irrigant with other war injured/infected anatomic sites, such as the brain, thorax, open joints, compound fractures, and wounds with gas gangrene (a notable killer in the pre-antibiotic era).

The experience of these early investigators utilizing HOCl, as well as the novel intraabdominal instillation techniques described by others,[50,51,65,68] formed the scientific and clinical basis of the application of continuous intermittent intraperitoneal instillation with HOCl in the case series presented. To assure a more thorough distribution of intraabdominal fluid instillation, the authors modified the TAC system with the application of the tube set. This configuration affords an effective method for irrigation delivery/fluid removal with a predetermined dwell time, frequency, and duration. The off-label use of this system allows for the efficient instillation of a topical solution, as described by Sibaja.[50] By virtue of its inherent properties, the use of HOCl to lavage the abdomen provides the surgeon with a more effective means to eliminate prokaryotic pathogens, associated biofilm, and exudate beyond the known limited effects of normal saline. However, if HOCl is not immediately available, the use of normal saline is an acceptable alternative.

Comments

3090D553-9492-4563-8681-AD288FA52ACE

processing....