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Septic : is it worth trying?

Author : Kate Murphy

Categories : Vets

Date : April 9, 2012

Kate Murphy looks at this challenging diagnosis from the perspective of an internal medic, suggesting approaches to treatment and reducing risks

SEPTIC peritonitis is a diagnosis that results in many clinicians groaning internally. It is not a good disease, but this article will try to highlight aspects of management that may improve the diagnosis and treatment of this condition.

Reported survival rates for patients with septic peritonitis are very variable and range from 50 per cent to 80 per cent, but it is very difficult to compare studies and even more difficult to use this information clinically.

Peritonitis can be caused by a number of factors, including infectious agents (bacteria, viruses and fungi) and noninfectious agents (chemical, such as bile and urine).

Bacterial peritonitis is a major cause of sepsis in dogs and an important cause in cats – and in the majority of cases represents a surgical emergency. However, there are certain types of peritonitis where this is not the case – for example, primary bacterial peritonitis or cats with feline infectious peritonitis – so distinguishing between a surgical emergency and a patient needing medical stabilisation is important.

Peritonitis can be either localised or diffuse, and primary or secondary.

Primary septic peritonitis is a spontaneous of the peritoneal cavity. This is reported to be more common in cats and is usually caused by a single organism, often gram-positive. It is

1 / 8 suggested that the contamination of the peritoneum may occur via haematogenous or lymphatic spread, or transmural migration from the gastrointestinal (GI) tract, or potentially spread from infected oviducts. The diagnosis is made by exclusion of any identifiable cause of the peritoneal contamination.

In contrast, secondary peritonitis – which is more common – is usually polymicrobial in nature and typically secondary to gastrointestinal perforation or abdominal surgery.

Localised peritonitis occurs when the contamination is well contained. This might be seen following abdominal surgery or with a GI foreign body resulting in perforation that is encapsulated by local tissue. Peritonitis becomes more diffuse, either from a failure to control localised peritonitis or when there is larger initial contamination.

The many causes of septic peritonitis are detailed in Table 1. The most common causes include loss of integrity of the GI tract, foreign body penetration of the intestinal tract, perforating gastrointestinal ulcers and surgical wound dehiscence. Dehiscence following intestinal surgery has been reported to occur in between three per cent and 12 per cent of cases. Perforation of the GI tract following administration of anti-inflammatory drugs is reported and is not simply associated with chronic administration; occurrences have been reported within 48 hours of starting treatment.

Septic peritonitis results in a marked inflammatory response in the , leading to increased capillary permeability and vasodilation. The microorganisms and the endotoxins they release cause significant damage to the peritoneum. The inflammation results in deposition of fibrin and production of fluid, which then has systemic effects on fluid balance. In the early stages of fluid development the fluid is clear, but it quickly becomes turbid due to the presence of protein and inflammatory cells. Experimentally, it has been shown that higher fluid volume reduces bacterial clearance and increases bacterial proliferation, and this can be important in our treatment consideration. A local response to peritonitis involves migration of the omentum to try to isolate the contamination, but also to aid clearance of the contamination. The GI tract does not relish this inflammatory soup and is often seen. Ileus can further complicate the situation and hypoperfusion of the gut can result in ischaemia and bacterial translocation.

Some of the inflammatory mediators released can result in systemic inflammation, decreased cardiac output, peripheral vasodilation and, ultimately, patients may develop systemic inflammatory response syndrome (SIRS), multiple organ dysfunction (MODS) and disseminated intravascular coagulation (DIC).

Clinical presentation

History and presentation can be variable, dependent on the underlying aetiology, severity and duration of the disease. Owners may report the animal’s lethargy, inappetence or anorexia, vomiting and a painful or distended abdomen.

2 / 8 Physical examination findings can also be very variable depending on the severity and duration of sepsis. In early sepsis patients, it might present in hyperdynamic shock, but later presentations will be more classic hypovolaemic shock.

Other features of shock these patients may also show include tachycardia (which is a good early indicator of hypoperfusion), altered mental status, dehydration and tachypnoea.

Cats are more challenging in their response to sepsis and often present with relative bradycardia. They less often show signs of abdominal pain.

Abdominal fluid may be obvious if there is marked abdominal distension and a fluid wave. However, a significant volume of fluid is required for these findings and so many patients with peritonitis will not have detectable abdominal fluid on physical examination.

Patients who have had previous surgery may have serosanguinous fluid dripping from their abdominal wound. This could be a consequence of low oncotic pressure or could reflect peritonitis. Sampling of the fluid is recommended. Any animal that has recently undergone abdominal surgery (particularly of the GI tract) and fails to recover normally (haemodynamically, improving mentation or appetite) should be critically evaluated to exclude septic peritonitis.

Measurement of blood pressure and monitoring of the trends is indicated and can be used to guide therapy; measurement of central venous pressure is even more useful for guiding fluid therapy.

Diagnostic investigation

A minimum database should be performed in all patients suspected of having peritonitis, and it can also be helpful to assess coagulation function (looking for evidence of disseminated intravascular coagulation), urinalysis and potentially acid-base status (including lactate).

Septic patients are more likely to have higher white cell counts and band neutrophil counts than nonseptic dogs, although peracute cases may have very low neutrophil counts.

Abdominal imaging can be helpful, but radiography is generally of limited benefit if there is marked fluid accumulation as it will show loss of serosal detail. Serosal detail can also be poor in young or very thin patients. Other features that may be evident on radiographs include the presence of a foreign body, abdominal mass or free gas. The sensitivity of radiography is generally low, although the finding of free gas is helpful (Figure 1). Free gas can be seen if abdominal surgery has been performed and can persist for up to one month. Thoracic radiographs should also be considered to rule out metastatic disease or complications including aspiration pneumonia.

Abdominal ultrasonography is very useful. It allows detection of small quantities of abdominal fluid and facilitates guided aspiration of pockets of fluid (Figure 2). Evaluation of the intestinal loops should

3 / 8 be performed looking for fluid or gas distension, luminal obstruction and all other organs should also be evaluated.

Abdominal fluid analysis plays a vitally important role and, therefore, either ultrasound-guided aspiration or blind abdominocentesis should be performed to obtain fluid. Diagnostic peritoneal lavage can be performed, but has become less often performed since the widespread adoption of ultrasonography. The fluid should be submitted for cytological analysis (nucleated cell count, smear analysis), biochemical analysis (protein, albumin) and culture (aerobic and anaerobic).

Further biochemical analysis of the abdominal fluid and comparison of levels to serum can be useful, for example, bilirubin for bile peritonitis, creatinine or potassium for uroabdomen, triglycerides and cholesterol for chyloabdomen. Also, a number of studies show the utility of glucose measurement in fluid and comparison to blood as an indicator of sepsis (fluid glucose greater than 1.0mmol/L lower than serum indicates sepsis) and similarly with lactate (fluid lactate greater than 2.5mmol/L and higher than blood indicates sepsis in dogs). If the patient has had recent abdominal surgery then neutrophilic inflammation will be found, but the neutrophils should be non-toxic and no bacteria or organic debris should be found. In septic peritonitis (Figure 3), signs of neutrophil toxicity are usually evident. However, it is not always easy to find organisms inside the cells. The use of glucose and lactate measurement in exudates is very useful in patients suspected to be septic, but no organisms are seen on cytology.

If the results of the above tests create a high suspicion of septic peritonitis, early surgical exploration is indicated, following stabilisation.

The major aims of treatment include:

• fluid replacement and volume expansion;

therapy;

• analgesia;

• treatment of the primary cause;

• drainage and lavage of the abdomen; and

• supportive care, such as nutrition, temperature management, treatment of adjunctive signs – for example, ileus or vomiting.

Fluid therapy

• Use large bore peripheral catheter to facilitate rapid fluid administration.

4 / 8 • Monitor the patient’s cardiovascular status and urine production to guide the effectiveness of fluid resuscitation.

• Establish end points for fluid resuscitation (for example, improved mentation, pink mucous membranes, capillary refill time, heart rate or improved pulse volume).

The approach to fluid resuscitation of critically ill patients is a review article in itself so the following are the author’s suggestions and readers will benefit from reading fluid therapy articles to deepen their understanding.

Hartmann’s solution will be a suitable choice of crystalloid for most patients. If the patient is hypovolaemic, administer boluses, for example, 10ml/kg over 10 minutes, and then reassess cardiovascular parameters.

If tachycardia and poor pulse quality were present and they have improved, then continuing fluid therapy at a slower rate could be appropriate. If they have not improved, repeat boluses should be given until cardiovascular parameters improve.

If, despite repeated crystalloid boluses, perfusion is not improving then a 5ml/kg to 10ml/kg bolus of colloid can be given and again repeated to effect. An alternative to colloids for intravascular volume resuscitation is hypertonic saline and small volumes can exert a significant effect on intravascular volume. It is generally used in large patients to facilitate rapid volume expansion.

Other fluids sometimes considered in septic patients include plasma, Oxyglobin (when available) and human serum albumin (HSA). A frequent misconception is that plasma can be used in hypoalbuminaemic patients to raise the colloid oncotic pressure (COP). However, approximately 10 times more plasma is required for the same effect on COP than, for example, HSA. Use of HSA is quite controversial, but might be considered in selected patients where low oncotic pressure is considered a priority to manage and readers are referred elsewhere for reviews of its use and its potential side effects. Plasma can have a role in patients with coagulation abnormalities.

If patients fail to respond to appropriate fluid therapy, use of vasopressors/inotropes can be considered, for example, dobutamine/dopamine.

Antibiotic therapy

The most common organisms isolated from septic peritonitis include Escherichia coli, Enterococcus species and Clostridium species and, therefore, should be chosen to provide gram- positive, game-negative and anaerobic activity.

The PROTECT guidelines developed by SAMSoc and BSAVA suggest the following regimes for treatment of septic peritonitis:

5 / 8 • amoxicillin-clavulanic acid or ampicillin and cefotaxime; or

• ampicillin and gentamicin; or

• clindamycin and enrofloxacin; or

• fluoroquinolone and ampicillin.

If anaerobic infection is suspected, addition of metronidazole is recommended. Since these patients are hypovolaemic, intravenous administration is recommended initially.

Analgesia

Opiates, such as buprenorphine, morphine or methadone, are the principal analgesic agents for these cases and may be given by bolus administration or by constant rate infusions. Additional analgesia in the form of lidocaine and/or ketamine infusions may also be required. Avoid non- steroidals. It is important not to underestimate the pain associated with peritoneal inflammation (particularly in cats).

Treatment of the primary cause, and drainage and lavage of the abdomen

At exploratory , the surgeon should make a thorough evaluation to try to identify the source of contamination (Figure 4) and use sound surgical principles to treat this effectively.

At the time of performing the surgery, consideration should also be given to facilitating the aftercare of the patient:

• thorough lavage and drainage at the time of surgery;

• ensure aseptic practice is adhered to, such as gloves and surgical kit change after treatment of the primary cause;

• placement of a feeding tube can facilitate postoperative nutrition – for example, consider an oesophagostomy or gastrostomy tube;

• consider ongoing drainage of the abdomen, such as placing an active suction drain (Figure 5) or Jackson-Pratt drain at the time of surgery.

Given experimental evidence that larger fluid volumes encourage bacterial growth and reduce bacterial clearance, drain placement seems logical. The drain should only remain in place for a few

6 / 8 days (at most) and aseptic technique should be used for drain management. Primary closure can be considered in patients with good results at surgery and with only localised inflammation.

Although open peritoneal drainage (OPD; Figure 6) is discussed in many texts, it is very labour intensive, has not been positively correlated with outcome and is generally difficult in any patient more than 5kg. Survival rates for OPD and primary closure are similar, but treatment costs will be very different. If vacuum-assisted closure (VAC) devices become more available they might have application in this situation.

Supportive care

Ensure your nursing care of the patient is all-encompassing and that early enteral nutrition is re- introduced in the patient’s recovery. If the patient is not eating voluntarily then anti-emetic therapy and treatment of ileus are important considerations.

If a feeding tube was placed at the time of surgery this can be used if voluntary intake is not seen. If a tube was not placed at surgery, consider placing a naso-oesophageal tube if there are no contraindications. Use of an appetite stimulant, such as mirtazapine, should also be considered. If there was a GI cause for the peritonitis, gastric protectants may be beneficial.

Relative adrenal insufficiency is a poorly described condition, which can be seen in critically ill patients. If a patient remains hypotensive despite adequate fluid resuscitation, this should be considered and physiologic doses of corticosteroids may be helpful.

Oxygen administration may be helpful in the stabilisation phase.

If hypoglycaemia is present, adding dextrose to the crystalloids is recommended.

If urine output is reduced, consider placing a urinary catheter and monitor output, aiming to maintain at least 1.0ml/kg/hour.

How we can reduce risk

Septic peritonitis is a difficult, challenging and sometimes depressing condition for veterinarians. It is also an extremely expensive condition to treat, so the main aim is to reduce the risks.

• Aim for early identification in at-risk patients – close attention to cardiovascular parameters including pulse pressure and blood pressure.

• Treat aggressively – in terms of fluids, antibiotics and surgery.

• Don’t be afraid of a negative exploratory laparotomy – if septic peritonitis is highly suspected, but

7 / 8 the fluid is not typical or the imaging is equivocal, remember that localised disease can confuse us. Of course, this could be a rare case of primary bacterial peritonitis.

• The prognosis for dogs and cats with septic peritonitis remains guarded and is worse in very young and very old patients; in those where the diagnosis is delayed; and in patients where the cause cannot be effectively treated and the contamination is more diffuse.

References are available upon request.

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