Intestinal Perforation Treatment & Management

The mainstay of treatment for intestinal perforation is surgery. ^[16] Surgery for intestinal perforation is contraindicated in the presence of general contraindications to anesthesia and major surgery, such as severe heart failure, respiratory failure, or multiorgan failure. It is also contraindicated if the patient refuses the operation and no evidence of generalized peritonitis exists. Finally, surgery is contraindicated if a contrast meal confirms spontaneous sealing of the perforation (eg, perforated duodenal ulcer) and the patient prefers a nonsurgical approach. ^[17]

Treatment is primarily surgical. Emergency medical care includes the following steps:

• Establish intravenous (IV) access, and initiate crystalloid therapy in patients with clinical signs of dehydration or septicemia
• Do not give anything by mouth
• Start IV administration of antibiotics to patients with signs of bloodstream infection; antibiotics should cover aerobic and anaerobic organisms; the goals of antibiotic treatment are to eradicate infection and to minimize related postoperative complications

However, if symptoms and signs of generalized peritonitis are absent, a nonoperative policy may be used with antibiotic therapy directed against gram-negative and anaerobic bacteria. ^{[18, 19]}

Antibiotics

Antibiotics have proved effective in decreasing the rate of postoperative wound infection and improving outcomes in patients with intraperitoneal infection and bloodstream infection.

Metronidazole is typically used in combination with an aminoglycoside to provide broad gram-negative and anaerobic coverage. It is reduced to a product that interacts with deoxyribonucleic acid (DNA) to cause a loss of helical DNA structure and strand breakage, resulting in inhibition of protein synthesis and cell death in susceptible organisms. Adult dosing is 7.5 mg/kg IV before surgery. Pediatric dosing is 15-30 mg/kg/day IV divided bid/tid for 7 days. Metronidazole is a pregnancy category B drug.

Gentamicin is an aminoglycoside antibiotic with gram-negative coverage. It is used in combination with both an agent against gram-positive organisms and one that covers anaerobes. Although it is not the drug of choice, it should be considered if penicillins or other less toxic drugs are contraindicated, when clinically indicated, and in mixed infections caused by susceptible staphylococci and gram-negative organisms.

Gentamicin dosing regimens are numerous; the dosage is adjusted on the basis of creatinine clearance (CrCl) and changes in volume of distribution. It may be given IV or intramuscularly (IM). In adults, the loading dose before surgery is 2 mg/kg IV; thereafter, the dosage is 3-5 mg/kg/day divided tid/qid. In infants, the dosage is 7.5 mg/kg/day IV divided tid. In children, the dosage is 6-7.5 mg/kg/day IV divided tid. Gentamicin is a pregnancy category C drug.

Cefotetan is a second-generation cephalosporin that inhibits bacterial cell wall synthesis by binding to one or more of the penicillin-binding proteins. It inhibits the final transpeptidation step of peptidoglycan synthesis, resulting in cell wall death. Adult dosing is 2 g IV once before surgery. In children younger than 3 months, dosing is not established. In those older than 3 months, dosing is 30-40 mg/kg IV once before surgery. Cefotetan is a pregnancy category B drug.

Cefoxitin is also a second-generation cephalosporin that inhibits bacterial cell wall synthesis by binding to one or more of the penicillin-binding proteins. It inhibits the final transpeptidation step of peptidoglycan synthesis, resulting in cell wall death. Adult dosing is 2 g IV once before surgery, followed by 4 doses of 2 g IV q4-6hr. In children younger than 3 months, dosing is not established. In those older than 3 months, dosing is 30-40 mg/kg IV before surgery, followed by 3 doses of 2 g IV q4-6hr for 24 hr. Cefoxitin is a pregnancy category B drug.

Ertapenem is indicated for complicated intra-abdominal infections in adults and children aged 3 years or older. It is a carbapenem that inhibits cell-wall synthesis by binding to penicillin-binding proteins. It is resistant to most beta-lactamases. Dosing in adults and adolescents is 1 g IV or IM once daily for 5-14 days. The dosage for children aged 3-12 years is 15 mg/kg IV or IM q12hr for 5-14 days.

Eravacycline is a synthetic fluorocycline antibiotic belonging to the tetracycline class. It disrupts bacterial protein synthesis by binding the 30S ribosomal subunit, thus preventing incorporation of amino acid residues into elongating peptide chains. It is indicated in adults for treatment of complicated intra-abdominal infections caused by the following susceptible bacteria:

• E coli
• Klebsiella pneumoniae
• Citrobacter freundii
• Enterobacter cloacae
• Klebsiella oxytoca
• Enterococcus faecalis
• Enterococcus faecium
• Staphylococcus aureus
• Streptococcus anginosus group
• Clostridium perfringens
• Bacteroides species
• Parabacteroides distasonis

Dosing is 1 mg/kg IV every 12 hours for 4-14 days. Dosage modifications are required in patients with severe hepatic impairment or if coadministered with strong CYP3A inducers. Approval for complicated intra-abdominal infections was based on results from the IGNITE-1 clinical trial (N = 541), which demonstrated that eravacycline was noninferior to ertapenem. ^[20]

The goals of surgical therapy are as follows:

• To correct the underlying anatomic problem
• To correct the cause of peritonitis
• To remove any foreign material in the peritoneal cavity that might inhibit WBC function and promote bacterial growth (eg, feces, food, bile, gastric or intestinal secretions, blood)

Operative details

Preoperatively, correct any fluid or electrolyte imbalance. Replace extracellular fluid losses by administering Hartmann solution or a similar solution that has an electrolyte composition similar to plasma. Central venous pressure (CVP) monitoring is essential in critically ill and/or elderly patients, in whom cardiac impairment may be exacerbated by large fluid loss.

Administer systemic antibiotics (eg, ampicillin, gentamicin, or metronidazole), making a best estimation regarding the likely organisms. Nasogastric suction is required to empty the stomach and reduce the risk of further vomiting. Urinary catheterization is used to assess urinary flow and fluid replacement. Administer analgesics, such as morphine, in small IV doses, preferably as a continuous infusion.

Operative management depends on the cause of perforation. Perform urgent surgery either on patients not responding to resuscitation or following stabilization and maintenance of adequate urine output. All necrotic material and contaminated fluid should be removed and accompanied by lavage with antibiotics (tetracycline 1 mg/mL). Decompress distended bowel via a nasogastric tube.

Laparoscopic or laparoscopic-assisted (minilaparotomy) surgery is also being increasingly performed, with outcomes comparable to those of conventional laparotomy. ^[21] Experience and advances in accessories have enabled endoscopic repair of a significant number of intestinal perforations, such as iatrogenic perforation. Management of such cases must be individualized to the patient.

In a study involving 934 patients with sigmoid diverticulitis, Ritz et al found that the risk of free perforation in acute sigmoid diverticulitis decreases with the increases in the number of previous episodes of sigmoid diverticulitis. They concluded that the first episode has the highest risk for a free perforation. Therefore, the indication for colectomy should not be made on the basis of the potential risk of free perforation. ^[22]

Intravenous replacement therapy

The aim of IV replacement therapy is to maintain intravascular volume and hydrate the patient. Monitor by CVP measurement and urinary output.

Nasogastric drainage

Perform nasogastric drainage continuously until drainage becomes minimal. At that stage, the nasogastric tube may be removed.

Antibiotics

Continue administration of the antibiotics commenced preoperatively unless the results of cultures taken at the time of the operation reveal that the causative organisms are resistant to them.

The goal of antibiotic therapy is to achieve levels of antibiotics at the site of infection that exceed the minimum inhibitory concentrations for the pathogens present.

In the presence of intra-abdominal infections, GI function is often impaired; therefore, oral antibiotics are not efficacious, and intravenous antibiotics are recommended.

If no obvious improvement in the patient's condition occurs within 2-3 days, consider the following possibilities:

• The initial operative procedure was inadequate.
• Complications have occurred.
• A superinfection has occurred at a new site.
• The dose of antibiotic is inadequate.
• The antibiotics used do not provide adequate coverage for anaerobes and gram-negative organisms.

Analgesics

Analgesics, such as IV morphine, should be given continuously or in small doses at frequent intervals.

Wound infection rates correlate with the bacterial load in the bowel; accordingly, this complication occurs more often with colonic perforation (eg, perforated diverticulitis). The judicious use of prophylactic antibiotics has been demonstrated to reduce the incidence of wound infection in contaminated and potentially contaminated wounds.

Wound failure (partial or total disruption of any or all layers of the operative wound) may occur early (ie, wound dehiscence) or late (ie, incisional hernia). The following factors are associated with wound failure:

• Malnutrition
• Sepsis
• Uremia
• Diabetes mellitus
• Corticosteroid therapy
• Obesity
• Heavy coughing
• Hematoma (with or without infection)

Localized abdominal abscess may develop.

Multiorgan failure and septic shock may develop. Septicemia (bloodstream infection) is defined as proliferation of bacteria in the bloodstream resulting in systemic manifestations such as rigors, fever, hypothermia (in gram-negative septicemia with endotoxemia), leukocytosis or leukopenia (in profound septicemia), tachycardia, and circulatory collapse. Septic shock is associated with a combination of the following:

• Loss of vasomotor tone
• Increased capillary permeability
• Myocardial depression
• Consumption of WBCs and platelets
• Dissemination of powerful vasoactive substances, such as histamine, serotonin, and prostaglandins, resulting in capillary permeability
• Complement activation and damage of capillary endothelium

Gram-negative infections are associated with a much worse prognosis than gram-positive infections, possibly because of associated endotoxemia.

Renal failure and fluid, electrolyte, and pH imbalance may occur.

Gastrointestinal mucosal hemorrhage is usually associated with failure of multiple organ systems and is probably related to a defect in the protective gastric mucosa.

Mechanical obstruction of the intestine is most often caused by postoperative adhesions.

The following factors may cause a predisposition to postoperative delirium:

• Advanced age
• Drug dependency
• Dementia
• Metabolic abnormalities
• Infections
• Previous history of delirium
• Hypoxia
• Intraoperative/postoperative hypotension

For patients treated with a nonsurgical approach, follow-up care consists of the following:

• If the pain and fever settle within a few days, the patient can go home with a barium enema and sigmoidoscopy to be performed on an outpatient basis a few weeks later
• Routinely perform colonoscopy if any doubt about the possibility of malignancy exists after barium enema examination
• If the patient continues to be pyrexial and the pain does not settle or the lower abdominal mass is enlarged, ultrasonography and a water-soluble contrast enema may be necessary
• If abscess is visible on ultrasound examination, it may be drained under ultrasonographic guidance
• If the infection process fails to settle despite adequate conservative treatment, operation is indicated (primary resection, irrigation, and primary anastomosis)