Intraabdominal Lavage of Hypochlorous Acid: A New Paradigm for the Septic and Open Abdomen

Introduction. Management of the open abdomen (OA) has rapidly evolved over the last several decades due to the improved understanding of the underlying pathophysiology of patients with an OA, adoption of damage control surgery, and the use of temporary abdominal closure (TAC) techniques for this patient population. The TAC utilizing negative pressure has been successful for managing patients with an OA with improved time to closure. Recent studies have started to examine the use of TAC in conjunction with negative pressure wound therapy with instillation and dwell time (NPWTi-d) for the management of the OA. Objective. This case series illustrates the capability, safety, and clinical effectiveness of TAC/NPWTi-d with hypochlorous acid (HOCl) solution. Materials and Methods. Three successfully treated cases describe the use of NPWTi-d using HOCl solution for the management of patients with a septic OA. Results. This initial experience suggests instillation of HOCl through the tubing set, in conjunction with the TAC device, is safe and easy to use. This technique decreased the need for more frequent OA lavages in the operating room (OR) after the index procedure, as well as the associated concomitant risks of transporting patients who are critically ill between the SICU and OR. No acute complications related to the TAC device with HOCl were noted. Conclusions. Based on the results of this study, the authors believe instillation through the TAC device may be the next evolution in the use of abdominal NPWT and programmed intermittent lavage of the peritoneal cavity represents an effective method in the care of patients with a septic OA.

Direct fluid irrigation of fluid into the peritoneal cavity (abdominal washout) has been an integral part of the management of the septic open abdomen (OA). This approach has been shown to assist in the removal of bacteria, some inflammatory mediators, and other contaminants commonly found in this setting.¹ Abdominal washout is best performed in the operating room (OR). In some patients who are critically ill with a septic OA, this may not be feasible. The authors present 3 cases that describe the use of negative pressure wound therapy with instillation and dwell time (NPWTi-d) using hypochlorous acid (HOCl) solution combined with temporary abdominal closure (TAC) for managing patients with a septic OA. 

The authors routinely use TAC NPWTi-d for all patients with a septic OA. After a careful and thorough assessment of the known efficacy and safety of Vashe Wound Solution (Urgo Medical North America, Fort Worth, TX), this was selected as the preferred HOCl irrigant in this clinical setting.

The Maricopa Integrated Medical System’s Institutional Review Board (Phoenix, AZ; now known as Valleywise Health) approved an expedited review of this case series.

Materials

The authors present 3 cases of patients with septic OAs that were managed with intraabdominal NPWTi-d utilizing a tubing set (V.A.C. VERAT.R.A.C. DUO Tube Set; KCI, San Antonio, TX) in conjunction with a TAC device (ABTHERA Open Abdomen Negative Pressure Therapy System; KCI). Wounds were instilled with the aforementioned HOCl solution. 

Technique

The techniques described in this report are of off-label uses from the manufacturers’ (KCI and Urgo) recommendations. The authors have developed a proposed TAC with NPWTi-d Protocol.

The initial experience, as demonstrated by this case series, suggests instillation of HOCl through the tubing set in conjunction with the TAC device is safe and easy to use. This technique allowed for the use of a timed, pre-programmed, and repeated instillation of a defined quantity of topical solution in the surgical intensive care unit (SICU). This decreased the need for more frequent OA lavages in the OR after the index procedure, as well as the associated concomitant risks of transporting patients who are critically ill between the SICU and OR. No acute complications related to the TAC device with HOCl were noted.

Case 1

A 59-year-old man with diabetes presented to the emergency department (ED) with generalized abdominal pain and lactic acidosis, coupled with multisystem organ failure, including acute respiratory failure (ARF), acute kidney injury (AKI), hepatic encephalopathy, and septic shock. The patient was emergently intubated; an emergent abdominal/pelvis computerized tomography (CT) with oral contrast showed a thickened small bowel and sigmoid colon (Figure 1A). The patient underwent a lower gastrointestinal endoscopy for colonic decompression and was diagnosed with ischemic colitis. 

Despite initial stabilization with intravenous (IV) resuscitation and a trial of nonoperative management, the patient developed abdominal compartment syndrome within 72 hours of SICU admission. The patient underwent an emergent exploratory laparotomy at 72 hours post admission. A gangrenous, toxic megacolon and gangrenous cholecystitis were noted (Figure 1B-1D). The patient required small bowel adhesiolysis, subtotal colectomy, open cholecystectomy, and 1 L of HOCl abdominal washout followed by placement of sodium hyaluronate and carboxymethylcellulose bioresorbable membrane (Seprafilm Adhesion Barrier; Sanofi-Aventis US LLC, A Sanofi Company, Bridgewater, NJ) (Figure 1C). Damage control surgery (DCS) devices were applied to the OA (Figure 1E) for TAC for subsequent 3-L lavage of normal saline with a 10-minute dwell time using the aforementioned protocol. 

The patient returned to the SICU for continued resuscitation. On postoperative day (POD) 5, the patient underwent an end ileostomy with an abdominal washout. Pink, healthy small bowel and distal sigmoid stumps were noted, and no intraperitoneal abscesses or fibrin depositions were found. The abdominal cavity was closed by primary fascial closure. The skin was left open, and a sterile dressing was applied. The patient was subsequently weaned from the ventilator and was discharged on hospital day (HD) 36 to a skilled nursing facility where, upon follow-up, he continues to remain stable with no wound complications.

Case 2

A 62-year-old woman with diabetes, an insulin dependency, chronic kidney failure, and congestive heart failure (CHF) with an ejection fraction of 25%, presented to the ED with abdominal pain and altered mental status. She was on antiplatelet therapy, including clopidogrel bisulfate (PLAVIX; Bristol-Myers Squibb, New York, NY) and chronic steroids for a noted meningeal mass. Abdominal/pelvic CT scans revealed pneumoperitoneum and small bowel thickening (Figure 2A). Her resuscitation included IV fluids, antibiotics, stress-dose steroids, platelet transfusion, and desmopressin acetate (DDAVP; Ferring Pharmaceuticals Inc, Parsippany, NJ).

An emergent, exploratory laparotomy, done immediately upon presentation, revealed a mid-sigmoid colon perforation with feculent peritonitis and multiple intraabdominal and pelvic abscesses with fibrinous exudate, coupled with a necrotic dome of the urinary bladder (Figure 2B-2D). An extensive adhesiolysis, partial sigmoid, and bladder resection with primary repair of the urinary bladder dome were performed, followed by a lavage of the purulent abdomen utilizing 3 L of Bacitracin (Pfizer Inc, New York, NY) solution, followed by 1 L of HOCl with a 5-minute dwell time before suction removal. Sodium hyaluronate and carboxymethylcellulose bioresorbable membrane were placed within the abdomen, followed by the TAC device for intermittent intraperitoneal instillation, as per the authors’ protocol, initiated in the OR (Figure 2E). The patient was admitted to the SICU postoperatively for further resuscitation. After 48 hours, the patient underwent a second abdominal washout with saline and HOCl, during which a small area of necrotic bladder was resected and repaired. A subsequent TAC was placed over the OA utilizing the same TAC system, as previously described in the protocol.

By POD 5, the patient underwent a third exploratory laparotomy, which showed minimal bowel wall edema and no purulence. Therefore, the descending colon and sigmoid remnants were mobilized for a functional, end-to-end stapled anastomosis, which was wrapped/reinforced with the abdominal omentum. 

Following abdominal lavage, another TAC placement over the OA was used with the same TAC system configuration for the utilization of the instillation protocol. On POD 12, intraoperative assessment revealed no anastomotic leakage, with clearance of all fibrinous exudates (Figure 2F, 2G). The abdominal incision was closed utilizing existing native fascia, and an incision management system (PREVENA Incision Management System; KCI) was applied to the stapled skin incision. The patient showed no further signs of sepsis, was successfully weaned from the ventilator, tolerated an enteral diet, and progressed to normal bowel movements. On HD 14, she was discharged to a long-term acute care facility.

Unfortunately, 4 days following discharge, the patient developed ARF, believed to be secondary to her CHF, and possible subclinical aspiration, which required intubation. A chest CT scan revealed multiple areas of pneumonitis and atelectasis, while the abdominal/pelvic CT scans did not reveal any intraabdominal pathology or anastomotic leak. The patient’s condition continued to require ventilator management for which the family requested palliative care; comfort care was instituted, and the patient subsequently died on POD 20 following initial surgery upon presentation.

Case 3

A 76-year-old woman with dementia presented with severe sepsis, AKI, and worsening encephalopathy. She had generalized abdominal pain; an abdominal/pelvic CT without contrast showed extensive free intraperitoneal air (Figure 3A-3C). The patient underwent an emergent laparotomy, which revealed diffuse peritonitis from a perforated appendix, accompanied with a large pelvic abscess, multiple interloop abscesses, and diffuse, intraabdominal fibrinous exudates (Figure 3D, 3E). An appendectomy, small and large bowel resection adhesiolysis, and an open cholecystectomy for an ischemic appearing gallbladder were performed. Drainage of the pelvic/interloop abscesses also was done. Intraabdominal lavage was performed, which included 2 L of HOCl for a 10-minute dwell, followed by suction removal and then placement of sodium hyaluronate and carboxymethylcellulose bioresorbable membrane and the TAC device, with the previously described instillation protocol (Figure 3F). 

On POD 3, the patient returned to the OR for another abdominal exploration, peritoneal washout, and primary closure of the abdomen. There was no evidence of intraperitoneal abscesses or fibrin deposition. The patient was weaned from the ventilator and began tolerating a regular diet. She was discharged on POD 17 to a skilled nursing facility. The patient continues to improve and remains stable upon clinical follow-up.

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 al⁸ demonstrated dose-related disruption and killing of biofilm-producing microorganisms at HOCl dilutions ranging from 1:32 to 1:16. The authors⁸ 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 10⁶ 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 10⁵, whereas the HOCl-irrigated wounds remained at 10² 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 al⁴⁵ 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 al⁵¹ 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 al⁵⁰ 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 al⁶⁵ 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 Fraser⁶⁶ 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 al⁶⁷ 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 described⁶⁶ 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.

The present case series is inherently limited in scope. The available literature describing the use of intraabdominal NPWTi-d with HOCl is sparse. The authors recommend a large, multicenter study comparing the present technique with other methods of management of the septic OA be performed. 

Based on the results of this study, the authors believe instillation through the TAC device may be the next evolution in the use of abdominal NPWT and that programmed intermittent lavage of the peritoneal cavity represents an effective method in the care of patients with a septic OA. This revolutionary approach may potentially decrease the number of operative abdominal re-explorations and provide more effective intraperitoneal sepsis control by reducing the concentration of intraabdominal microbial pathogens and proinflammatory mediators. Based on this limited study, the authors conclude that intraabdominal NPWTi-d with HOCl was useful in the care of patients with a septic OA. 

These 3 cases represent common clinical manifestations of the septic abdomen from a variety of sources and are illustrative of the types of general surgical patients who may benefit from this modified approach. This off-label adaptation of the TAC device and instillation system show this form of TAC can be used as a 2-way therapy with instilling HOCl as the intraabdominal lavage fluid. The lack of eukaryotic cellular toxicity and unique antibacterial, antifungal, and biofilm-disrupting properties in HOCl effectively inhibit the bacteria growth and biofilm development. The techniques used in this case series represent a potential paradigm shift in the management of the septic OA. 

Authors: Luis G Fernández, MD, KHS, KCOEG, FACS, FASAS, FCCP, FCCM, FICS¹; Marc R. Matthews, MD, FACS²; and Lawton Seal, MS, PhD³

Affiliations: ¹University of Texas Health Science Center, Tyler, TX; ²Maricopa Integrated Health System, Phoenix, AZ; and ³University of North Texas, Denton, TX

Correspondence: Luis G. Fernández, MD, KHS, KCOEG, FACS, FASAS, FCCP, FCCM, FICS, Professor of Surgery, UT Health East Texas Physicians Tyler, Department of Surgery, 6801 Hollytree Circle, Tyler, TX 75703; thebigkahuna115@gmail.com; thebigkahuna1@suddenlink.net 

Disclosure: Dr. Fernández and Dr. Matthews are paid speakers for KCI (San Antonio, TX). Dr. Fernández serves as a speaker for Urgo Medical (Fort Worth, TX). The authors disclose no financial support for this study.