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In this VetGirl blog, we review treatment for canine leptospirosis, including aggressive intravenous (IV) fluid therapy, appropriate antibiotic therapy, gastrointestinal support, supportive care, and monitoring.

Fluid therapy
In the leptospirosis patient, aggressive intravenous (IV) fluid therapy is indicated as many patients are often massively polyuric, dehydrated, and azotemic. In general, a balanced, maintenance, isotonic crystalloid (e.g., LRS, Norm-R) can be used at 2.5-4.5X maintenance, and monitoring of ins and outs may be necessary to guide treatment (based on the severity of polyuria seen in patients with leptospirosis). The patient should be assessed carefully to ensure that volume overload does not occur, particularly in patients with cardiopulmonary disease. Fluid therapy should be continued until azotemia and clinical signs resolve (typically 2-4 days); IV fluids should then be slowly tapered to ensure that polyuria has resolved and the patient can maintain hydration.

Goals of fluid therapy
Serial physical examination is imperative to adequately evaluate a patient’s hydration status—checking for return of skin turgor, appropriate weight gain, and moisture of mucous membranes. However, physical examination findings are subjective, and <5% dehydration is subjective and difficult to assess on physical examination. The concurrent use of evaluation of PCV/TS, blood glucose, blood urea nitrogen (BUN or AZO), weight, urine output (UOP), urine specific gravity (USG), and thirst can be used in conjunction with physical examination findings to better assess hydration status.

Packed Cell Volume/Total Solids, Blood Glucose, and Blood, Urea, Nitrogen (BUN/AZO)
Patients on IV fluids should have daily blood work (including PCV/TS, blood glucose, electrolytes, renal or biochemistry panel) assessed while hospitalized. Because patients often experience hemoconcentration when they are dehydrated (e.g., PCV/TS 55%/7.8 g/dl), the goal of fluid therapy is to ensure that these numbers improve with appropriate therapy (consistent with hemodilution). Ideally, the PCV/TS in a normal, systemically healthy patient on IV fluids at sea level should be 35%/5.0 g/dl. In fact, oxygen delivery is maximal at such a “hemodilute” PCV/TS, as there is less viscosity of red blood cells and “sludginess.” Note that some patients with leptospirosis may have a mild to moderate non-regenerative anemia; the goal should still be to hemodilute the patient, and total protein/solids should be used as a more appropriate guide in this situation. We can still evaluate the PCV/TS in abnormal, metabolically inappropriate patients. Classically, a 10% to 12% dehydrated, cachectic, geriatric cat with chronic renal failure may present to you with a PCV/TS of 28%/11 g/dl. Once that patient is adequately hydrated, the PCV/TS may decrease to 20%/7 g/dl, unmasking the anemia from lack of erythropoietin.

Urine Specific Gravity (USG)
In normal healthy patients, USG can be evaluated in patients on IV fluids to help assess hydration status. Ideally, USG should be measured before fluid administration to allow for evaluation of renal function. Dehydrated patients with concentrated urine demonstrate adequate renal function (cat > 1.040, dog > 1.025) – in other words, the kidneys are working and trying to absorb as much water from the urine as possible. Once started on IV fluids, normal, systemically healthy patients should have isosthenuric urine. Patients on IV fluids for > 6 to 12 hours should have adequate dilution of USG, and the ultimate goal of fluid therapy and adequate hydration should be USG of 1.015 to 1.018 on IV fluids. Patients on IV fluids with USG > 1.020 are still likely dehydrated and should be treated more aggressively with IV fluids if other parameters of dehydration persist (e.g., hemoconcentration). Hydration can be determined by assessing the color, volume, and USG of urine. A patient that is still dehydrated while hospitalized on IV fluids may have decreased UOP and dark-yellow urine (provided, for example, that no pigmentation, myoglobinuria, or bilirubinuria are present). This is a result of antidiuretic hormone release and renin-angiotensin stimulation, resulting in maximum absorption of free water and sodium. Unfortunately, in the leptospirosis patient, PU/PD may occur due to acquired nephrogenic diabetes insipidius, so utilizing USG as a guideline for hydration status will be difficult.

Urine Output (UOP)
UOP should be monitored carefully, particularly in azotemic patients with leptospirosis. Fluid therapy should be directed toward achieving a hydrated state and matching ins and outs, based on the patient’s UOP. Note that normal UOP is 1–2 ml/kg/hour, but many of these leptospirosis patients present with severe polyuria. Again, one can assess the hydration status of the patient by evaluating the volume and USG of urine. Excessive urination with dilute, clear urine may indicate copious or excessive IV fluid therapy, whereas hypersenthuria may suggest ongoing dehydration, and aggressive fluid resuscitation may be further warranted. If UOP is decreased (particularly in azotemic patients), fluid therapy and vasopressor support (to increase renal blood flow) should be initiated to prevent anuria (< 0.5 ml/kg/hour) or oliguria (< 1 ml/kg/hour). If UOP is decreasing and renal function is normal (based on creatinine, BUN, and pre–fluid therapy USG), the patient should be reassessed for hydration status, and fluid therapy adjusted as indicated.

• Normal UOP: 1–2 ml/kg/hour
• Oliguria: 0.5–1 ml/kg/hour
• Anuria: < 0.5 ml/kg/hour

Note that underlying diseases such as leptospirosis; postobstructive diuresis (posturethral obstruction); diabetes mellitus (with secondary osmotic diuresis due to glucosuria); diabetes insipidus; hyperthyroidism (increased glomerular filtration rate due to increased metabolic rate); and chronic renal failure (inability to adequately concentrate and absorb water) may result in dramatic water losses through the kidneys, and these patients may need a higher rate of fluids to compensate for ongoing losses. Likewise, these disease processes prevent us from differentiating renal versus prerenal disease on the basis of USG alone, as these patients have isosthenuria due to metabolic disease. Regardless, appropriate fluid therapy and urine monitoring (e.g., “measuring ins and outs”) may be necessary, particularly in azotemic, oliguric renal failure.

Antibiotic therapy
In the patient suspected of having leptospirosis, prompt, appropriate antibiotic therapy should be initiated (ideally after pre-treatment blood work has been submitted). Goals of antibiotic therapy is to eliminate leptospiremia and to eliminate leptospires from the renal tubular cells and renal carrier state). Appropriate antibiotics include penicillins (e.g., including ampicillin, amoxicillin, amoxicillin/clavulanic acid, penicillin, etc.) and doxycycline.1 In humans, the use of ceftriaxone and cefotaxime are also efficacious.1 The use of fluoroquinolones is controversial, as efficacy in a hamster model failed to clear leptospires from the kidneys and blood.13 Based on the ACVIM Consensus Statement, the antibiotic of choice is doxycycline (5 mg/kg PO or IV q. 12 hours for 2 weeks).1 Leptospires can shed in urine for months if appropriate antibiotic use is not implemented.

Gastrointestinal support
Azotemic patients should be treated with phosphate binders (e.g., aluminum hydroxide) if hyperphosphatemic, along with gastrointestinal protectants (e.g., omeprazole, pantoprazole, famotidine, sucralfate, etc.) for presumptive uremic gastritis. Anti-emetics (e.g., maropitant, ondansetron, dolasetron) should be implemented for patient comfort and to treat nausea.

• Maropitant: 1 mg/kg SQ q. 24 hours
• Ondansetron: 0.1-0.2 mg/kg IV q. 8-12 hours
• Dolasetron: 0.5-1 mg/kg SQ, IV q. 24 hours
• Metoclopramide: 0.1-0.5 mg/kg SC, IV q. 8 hours or 1-2 mg/kg/day as CRI IV

Gastric pH altering medication:
H2 blockers:
• Famotidine: 0.5-1 mg/kg IV, SQ q. 12-24 (least p-450)
• Ranitidine: 0.5-2 mg/kg, IV, PO, SQ q. 8-12 (moderate p-450)
• Cimetidine: 5-10 mg/kg IV, PO, SQ q. 6-8 (most p-450)

Proton-pump inhibitors:
• Omeprazole: 0.5-1 mg/kg PO q. 24 hours
• Pantoprazole: 1 mg/kg IV q. 24 hours

Sucralfate 100-1 g PO q. 8 hours

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