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Intraperitoneal povidone-iodine in experimental canine and murine peritonitis.

In dogs with appendicitis-peritonitis, intraperitoneal povidone-iodine caused death more rapidly than the instillation of saline solution. The bacterial content of canine peritoneal fluid increased with time. Although fewer bacteria were found in fluid from povidone-iodine-treated dogs, the differences were not statistically significant. Qualitative chemical analysis of peritoneal fluid revealed iodide, but not free iodine, 15 to 30 minutes after instillation of povidone-iodine. Iodine was present in the peritoneum at 2 hours but not at 3 or 6 hours. The antibacterial effect of povidone-iodine was demonstrated in mice challenged intraperitoneally with lethal doses of Escherichia coli. Povidone-iodine diminished mortality when injected immediately (p less than 0.005) but not when given 1 to 3 hours later. Immediate injection of povidone-iodine into mice lowered the number of E. coli by 3 logs. Injection of povidone-iodine 3 hours after bacterial challenge lowered the number of E. coli by only 1/3 log. This lesser bactericidal effect in mice is attributed to greater dispersal and sequestration of bacteria throughout the peritoneal cavity with time and with inactivation of povidone-iodine by reduction to iodide in vivo. In dogs with appendicitis-peritonitis, the more rapid death after treatment with povidone-iodine was not associated with differences in peritoneal microflora but with peritoneal absorption of excessive amounts of iodide.

Animals

Evaluation of "instant" preparation of the colon with povidone-iodine.

The antimicrobial effect of 20 minutes exposure to 10% povidone-iodine solution and to 5% neomycin-erythromycin solution was evaluated in vitro in 6 suspensions of dog feces. Povidone-iodine eliminated aerobic growth (P less than 0.001) and reduced anaerobes 4.01 +/- 1.06 (P less than 0.02); C. perfringens was the only anaerobic organism grown. Forty unprepared dogs underwent resection of the sigmoid colon and primary anastomosis. Twenty received normal saline and 20 povidone-iodine injected intraluminally immediately before resection. The colon contents of povidone-iodine treated dogs grew only 0.07 +/- 0.07 aerobes and 3.74 +/- 0.49 anaerobes (all Clostridia) (log10/ml colon contents) (P less than 0.001). All povidone-iodine dogs survived 3 weeks with no anastomotic leaks; three controls died from anastomotic leak within the first week (P = 0.12). Reexploration of survivors revealed less perianastomotic reaction in the povidone-iodine group. Twenty minutes exposure to povidone-iodine produced a significant decrease in bacterial counts in vitro and in unprepared sigmoid colon. No adverse effects were demonstrated.

Animals

Intraperitoneal povidone-iodine in experimental peritonitis.

Two experimental models were utilized to study the efficacy of intraperitoneal povidone-iodine in an established peritonitis. In both models, there was a 100% mortality in the povidone-iodine treated group. In laboratories which have reported favorable results, the animals were treated before peritonitis was allowed to develop. Clinical studies with povidone-iodine lavage have used dilute solutions which did not remain in the infected space. The effectiveness of this method was probably due to mechanical continuous irrigation. Our toxicity studies showed povidone-iodine to be fatal in normal animals in dosages exceeding 4.0 ml/kg. However, a dose of 2.0 ml/kg, which was nontoxic in normal animals, was fatal in animals with peritonitis. This study strongly suggests that the intraperitoneal administration of povidone-iodine can be fatal when the animal is compromised by peritonitis. The mechanism of this effect is unclear. On the basis of these studies, the intraperitoneal administration of povidone-iodine cannot be recommended for therapy of peritonitis.

Animals

A study of the effect of povidone-iodine on polymorphonuclear leucocyte chemotaxis.

Studies were made of the effect of povidone-iodine on polymorphonuclear leucocyte chemotaxis. Polymorphonuclear leucocytes were incubated with various concentrations of povidone-iodine and allowed to migrate across a membrane towards a chemotactic agent. Chemotactic movement was found to decrease as the concentration of povidone-iodine rose, 75 micrograms/ml completely inhibiting all movement. A concentration of 10 micrograms/ml of povidone-iodine was found actively to repel the white cells. In vivo studies in mice showed a reduction in polymorphonuclear leucocytes at wound surfaces in the presence of povidone-iodine dry powder spray.

Animals

Bacteriologic and systemic effects of intraoperative segmental bowel preparation with povidone iodine.

A technique for intraoperative segmental preparation of the large bowel, using 10% povidone iodine, was evaluated in 25 patients undergoing elective colon resection. Qualitative and quantitative bacteriology was obtained from the normal bowel content and from segments of colon treated with povidone iodine or normal saline. Forty-five of 50 segments treated with povidone iodine demonstrated no growth, whereas the segments injected with normal saline maintained bacterial counts of 3.5 x 10(8) colony forming units per milliliter. There were no septic complications in this group of patients and the levels of triiodothyroninc and thyroxin remained unchanged despite a substantial absorption of iodine, as demonstrated by protein-bound iodine determinations. Intraoperative segmental preparation of the colon with 10% povidone iodine is a simple technique that may be useful in the enhancement of other methods of bowel preparation by further reducing the endogenous bacterial inoculum at the time of transection of the colon.

Adult

A study of the effect of povidone-iodine on wound healing.

The effect of dry powder povidone-iodine (Disadine D.P.) on wound healing was assessed experimentally and clinically. It did not interfere with wound healing macroscopically, histologically or mechanically in Wistar rats. One hundred and one patients undergoing 'clean' elective surgery were included in the controlled clinical study and povidone-iodine did not affect wound healing in any way. In the control group 4% of patients developed infection compared with none of those sprayed with povidone-iodine. No adverse reaction to povidone-iodine was seen in either study. This antiseptic offers a safe alternative to antibiotics for use at operation whenever there is risk of wound infection from operative bacterial contamination.

Abdomen

Intraperitoneal irrigation with povidone-iodine solution for the prevention of intra-abdominal abscesses in the bacterially contaminated abdomen.

A prospective randomized investigation was undertaken, involving 168 consecutive patients undergoing laparotomy for conditions accompanying bacterially contaminated peritoneal cavities, to evaluate the effectiveness of povidone-iodine irrigation of the peritoneum in preventing the development of intra-abdominal abscesses. In the treatment group irrigated with povidone-iodine solution, 0.1 per cent available iodine, one of 80 patients had an abscess, 1.3 per cent, while, in the saline solution irrigated control group, nine of 88 patients had abscesses, 10.2 per cent, p less than 0.05. Although the serum iodine levels were elevated 24 hours after intraperitoneal irrigation with povidone-iodine solution, iodine levels returned to near normal by 72 hours. Thyroxine levels showed no major changes. No complications resulting from the use of povidone-iodine were recognized.

Abscess

Povidone-iodine: an adjunct in the treatmen of wound infections, dehiscences, and fistulas in head and neck surgery.

Extensive research has been done to elucidate the cellular and biochemical events of a healing wound. Similarly, new techniques are continually being investigated which would stimulate and augment the reparative process. This paper describes the uses and biochemistry of povidone-iodine which has gained widespread acceptance as a surgical preparation. However, its use as a topical agent for treating head and neck wound infections, dehiscences, and salivary fistulas has gained little recognition. Povidone-iodine is a unique compound formed by binding free iodine to polyvinylpyrrolidone. Previously, the toxic effects of iodine limited its use to preparation of the skin for surgery. When bound to the pyrrolidine molecule, iodine becomes water soluble and markedly less toxic. As a result, the broad antimicrobial spectrum of iodine may be used topically to control wound sepsis. It can be applied to mucosal surfaces without producing burns. The brown color acts as an indicator of its clinical effectiveness. When the dressings become light yellow or pale, free iodine is no longer being released and the dressing should be changed. Povidone-iodine is not a panacea for correcting interruption in the healing process during the postoperative period. The basic management of wound infections, dehiscences, and fistulas remains unchanged. Incision and drainage, debridement and flap contracture, lateralization, and diversion are necessary to initiate the healing process. Familarity with each phase of healing provides the basis for managing each of these surgical problems. Topical povidone-iodine not only controls wound sepsis but augments wound healing. The physiologic correlation with each phase of wound healing for these various surgical problems is elaborated and clinical cases presented.

Administration, Topical

Prophylactic interparietal povidone-iodine in abdominal surgery.

This study sought to determine in a district general hospital (a) the frequency and nature of bacterial contamination at operation, (b) the incidence of consequent infection and (c) the prophylactic effect, if any, of interparietal povidone-iodine against postoperative wound infection. Bacterial contamination was shown in 49 per cent of all the abdominal surgical wounds at the end of operation. From 61 per cent of the subsequently infected wounds, organisms identified as contaminants at operation were again found. Interparietal instillation of povidone-iodine resulted in a statistically significant reduction in wound infection (P less than 0.01) in treated patients compared with untreated, randomized, matched controls. It was of significant value in cases of intestinal resection and peritonitis, in obese patients and in those with paramedian incisions. Laboratory studies indicate that povidone-iodine does not induce bacterial resistance. This chemical antibacterial agent may thus provide a preferable alternative to antibiotics in preventing such infections.

Abdomen

Prevention of intraperitoneal adhesions: a comparison of noxythiolin and a new povidone-iodine/PVP solution.

Peritoneal adhesions were induced in 250 female Wistar rats by the excision and closure of a right lower quadrant parietal peritoneal defect. After closure of the defect each rat was randomly allocated to one of five treatment groups: A, control with no instillate; B, control with Ringer solution; C, noxythiolin 0.5 per cent solution; D, noxythiolin 1 per cent solution; E povidone-iodine/PVP solution. Two millilitres of the appropriate solution were injected into the peritoneal cavity just before closure of a standard 4-cm midline incision. Assessment of adhesion formation was made at 1 week in ignorance of the treatment group. Noxythiolin 1 per cent was more effective than Ringer solution and noxythiolin 0.5 per cent in reducing the mean number of adhesions (P less than 0.05) but was inferior to povidone-iodine/PVP (P less than 0.05). Povidone-iodine/PVP solution significantly reduced the number of adhesions compared with the four other groups. In addition, it significantly reduced the mean length of attachment of each adhesion compared with the two control groups (P less than 0.001).

Animals

Prophylactic intraperitoneal povidone-iodine in alimentary tract surgery.

In controlled experiments intraperitoneal povidone-iodine significantly reduced the mortality of mice (p less than 0.01) and rats (p less than 0.01) with induced peritonitis. Povidone-iodine irrigation of the rat colon before and after anastomosis did not interfere with healing or inhibit peritoneal adhesion formation. However, a newly formulated povidone-iodine solution containing increased PVP significantly reduced adhesion formation in a controlled study in rats.

Animals

Complications of povidone-iodine absorption in topically treated burn patients.

One of the dangers of topical therapy in thermal injuries is absorption of the therapeutic agent with subsequent metabolic and toxic complications. Two patients, one 30 years old with a 75% burn, the second 72 years old with a 35% burn, were treated topically with povidone-iodine ("Betadine", pH 2.43). In both patients severe metabolic acidosis developed which could not be attributed to sepsis, hypovolaemia, renal failure, diabetes, lactic acidaemia, &c. The acidosis associated with the 75% burn required large amounts of sodium bicarbonate to maintain pH at 7.35 and a serum-bicarbonate concentration of 15 mmol/l (meq/l); serum-iodine was 48000 mug/dl (normal 4-8.5mug/dl). Acidosis in the second patient was not as severe, and serum-iodine concentration reached 17600 mug/dl. The rate of urinary excretion of iodine was 50.8 +/- 7.4 mg/dl and seemed to be fixed. Haemodialysis was very effective in reducing serum-iodine concentration. Povidone was also systemically absorbed. The persistent acidosis could be caused by absorption of the iodine or the acidic povidone-iodine. Until the aetiology of the acidosis and renal damage is more clear, iodophors should not be used topically for burns greater than 20% of the body surface or in the presence of renal failure.

Absorption

Use of chlorhexidine gluconate and povidone iodine mouthwashes in the treatment of acute ulcerative gingivitis.

A trial was conducted to compare the effectiveness of povidone iodine and chlorhexidine gluconate with buffered peroxyborate in the treatment of acute ulcerative gingivitis. After 20 patients had entered the trial and 11 had required additional therapy with metronidazole to control their symptoms, the study was terminated. Those patients receiving peroxyborate all showed a satisfactory improvement in clinical signs and symptoms. One patient each receiving povidone iodine or chlorhexidine reported a symptomatic improvement, although gingival ulceration was still apparent at 1 week. The remaining patients all required metronidazole therapy to control their symptoms. Povidone iodine and chlorhexidine gluconate therefore cannot be recommended for the treatment of acute ulcerative gingivitis.

Acute Disease

Colonic anastomosis healing. The effect of topical povidone-iodine.

The effect of povidone-iodine (0.1% available iodine) irrigation on colonic anastomosis healing was investigated in 196 Sprague-Dawley rats. Each end of the divided colon was irrigated with 5 ml of povidone-iodine solution or with an equal volume of normal saline before anastomosis and again after the anastomosis had been completed. Healing was assessed at 2, 4, 6, 8, 10, and 14 days after operation: macroscopically, mechanically, histologically and angiigraphically. Povidone-iodine irrigation did not impair healing in any way.

Administration, Topical

The effect of povidone iodine on plaque and salivary bacteria. A double-blind crossover trial.

A double blind crossover trial was carried out to assess the effect of povidone iodine on plaque accumulation in vivo and to measure the total salivary aerobes and anaerobes throughout the study. When compared to the placebo preparation, povidone iodine was without effect on plaque accumulation in all the subjects and there was a progressive increase in plaque throughout the 10-day periods. A 30 to 40 % overall reduction in aerobes and anaerobes occurred with the active preparation which was significant. There appears to be no indication for the use of povidone iodine as an adjunct to oral hygiene or in the treatment of chronic gingivitis.

Bacteria

The bacteriology of primary wound sepsis in potentially contaminated abdominal operations: the effect of irrigation, povidone-iodine and cephaloridine on the sepsis rate assessed in a clinical trial.

Two hundred and nine potentially contaminated abdominal operations were randomly allocated to prophylaxis with a single dose of 1 g cephaloridine intraincisionally, irrigation of the wound at the end of the operation with saline or spraying of the wound with povidone-iodine. In high risk operations (ileocolorectal or those in obese patients) the rate of major wound sepsis in those protected by cephaloridine was 3.8% compared with 13.2% in the irrigation and 16.7% in the povidone-iodine groups. In low risk operations no significant differences in sepsis rates were found. Bacteriological studies of incised organs, subcutaneous fat and pus showed that the majority of wound infections arose from endogenous sources. The outstanding problem remains that of prevention of contamination of the abdominal wall during surgery.

Abdomen

Hand-washing degerming: a comparison of povidone-iodine and chlorhexidine.

Two antiseptic preparations for hand washing were compared by the glove-juice method in a crossover study on 10 volunteers. The reference preparation was 7.5% povidone-iodine (Betadine Surgical Scrub); the test agent was 4% chlorhexidine gluconate combined with 4% isopropyl alcohol (Hibiclens). The experimental model included inoculation of the hands with a mixture of Serratia marcescens, Escherichia coli, Providentia stuartii, and Pseudomonas aeruginosa. The reference preparation achieved a reduction ratio in colony counts of 695 to 1 under the conditions of this study. The average postwash colony count after use of 7.5% povidone-iodine was significantly less than the preinoculation colony count. Logarithmic values, and the paired t test applied to them, showed a highly significant difference (p = less than 0.001) in favor of the degerming ability of the reference agent compared to the test agent. These data are of value in the selection of preparations for hand washing and may point the way to quantitative methods for other degerming studies.

Anti-Infective Agents, Local

Structure of polyvinylpyrrolidone-iodine (povidone-iodine).

Hydrogen triiodide adducts were prepared from N,N-dimethylacetamide, N-alkylpyrrolidone derivatives, and polyvinylpyrrolidone, and their structures were investigated by IR spectra and X-ray structure analyses and compared with the structure of povidone-iodine USP. The results suggest that the iodine in povidone-iodine USP is complexed by the polymer such that a proton is fixed via a short hydrogen bond between two carbonyl groups of two pyrrolidone rings and that a triiodide anion is bound ionically to this cation.

Chemical Phenomena