The Case: Puppy with Parvovirus Infection
HISTORYAn 8-week-old intact male miniature pinscher that had been adopted 3 days earlier from a private home was presented to the primary veterinarian for inappetence and lethargy of 24 hours’ duration. The referring veterinarian began treatment with 8 mg metronidazole q12h, Fortiflora probiotic (Nestle Purina) and Hill’s Prescription Diet a/d. The next day the puppy was re-presented for continued lethargy and was found to be hypothermic (97⁰F), hypoglycemic (67 mg/dL), and strongly positive for parvovirus antigen. The patient was transferred to a specialty emergency clinic:
Related Article: Feeding the Critically Ill, Anorectic Dog
PRESENTATION 1Physical examinationUpon presentation, the puppy was laterally recumbent, minimally responsive, and severely dehydrated.
Temperature: 95.4⁰F
Heart rate: 140 bpm
Respiratory rate: 20 bpm
Blood pressure: 110 mm Hg by Doppler
Weight: 0.78 kg (BCS 1/9)
Palpably thickened, fluid-filled intestines
DIAGNOSTICS & TREATMENT: DAYS 1–7Day 1
Blood glucose: 57 mg/dL (glucometer). Administered 1 mL 50% dextrose bolus IV
Hospitalization, Plasmalyte* + 5% dextrose + 40 mEq/L potassium chloride IV, dolasetron (0.5 mg q24h IV), ampicillin (20 mg q8h IV), famotidine (1 mg q24h IV)
Blood analysis (after 6 hr of fluids, dextrose CRI)
Sodium: 131 mEq/L (range, 142–150)
Potassium: 2.8 mEq/L (range, 3.4–4.9)
Chloride: 91 mEq/L (range, 106–127)
Glucose: 114 mg/dL (range, 60–115)
Blood urea nitrogen: 13 mg/dL (range, 10–26)
Hematocrit: 31% (range, 35–50)
A multiple electrolyte intravenous solution
pH: 7.34 (range, 7.35–7.45)
Packed cell volume/total solids: 33%/3.9 (ranges, 36–60/5.0–7.4)
White blood cells: 4.5 × 103/μL (range, 6–17)
Platelets: 42.6 × 104/μL (range, 20–50)
Blood type: DEA 1.1 positive
Related Article: The Case: Persistent Inappetence
Day 2The puppy was recumbent and dull throughout the morning. At about midnight, blood values as reported above remained the same. New values:
Creatinine: 0.2 mg/dL (range, 0.3–1.2)
Albumin: 1.7 g/dL (range, 2.1–3.6)
Alanine aminotransferase: 78 U/L (range, 8–75)
Lymphocytes: 1.1 X 103/μL (range, 0 .9–5)
At 3:00 AM, the first transfusion of hyperimmune plasma (8 mL DEA negative over 3 hours) was administered.
8:00 AM exam
Temperature: 99.4⁰F
Heart rate: 200 bpm
Painful abdomen
Bloody diarrhea, regurgitation overnight
Administered bolus of 18 mL crystalloid fluids IV, 1 mL 25% dextrose IV. Recheck:
Heart rate 90 bpm
Blood pressure: 95
Started metoclopramide CRI (1 mg/kg/d; 1 mL/hr).
9:00 AM blood values
Sodium: 132 mEq/L (range, 142–150)
Potassium: 2.9 mEq/L (range, 3.4–4.9)
Chloride: 99 mEq/L (range, 106–127)
Glucose: 42 mg/dL (range, 60–115)
Blood urea nitrogen: 8 mg/dL (range, 10–26)
Hematocrit: 24% (range, 35–50)
pH: 7.30 (range, 7.35–7.45)
10:00 AM: Hyperimmune plasma (2nd transfusion) 8 mL DEA negative over 2 hours
4:00 PM blood values
Sodium: 132 mEq/L (range, 142–150)
Potassium: 2.9 mEq/L (range, 3.4–4.9)
Chloride: 101 mEq/L (range, 106–127)
Glucose: 55 mg/dL (range, 60–115)
Blood urea nitrogen: 5 mg/dL (range, 10–26)
Hematocrit: 26% (range, 35–50)
pH 7.38 (range, 7.35–7.45)
Administered 1 mL 25% dextrose bolus; increased dextrose CRI to 7.5%. In the afternoon, puppy was brighter, with minimal diarrhea and one episode of regurgitation. No interest in eating.
Treatment:
Medications
Ampicillin (20 mg q8h IV)
Dolasetron (0.5 mg IV)
Enrofloxacin (8 mg q24h IV)
Metronidazole (8 mg q12h IV)
Famotidine (1 mg q24h IV)
Maropitant (0.8 mg q 24h SC)
Metoclopramide (1 mg/kg/day at 1 mL/hr)
Hetastarch (0.6 mL/hr IV)
Buprenorphine 0.007 mg IV (8:00 AM and 4:00 PM)
Fluids
Plasmalyte (5 mL/hr) + 7.5% dextrose and 50 mEq/L potassium chloride––all IV
Day 3Throughout the morning the puppy was brighter, with no interest in food, although he tolerated syringe feeding. Hemorrhagic diarrhea had been seen overnight, with one episode of regurgitation. Maintained normoglycemia overnight. Abdomenwas comfortable.
2:00 AM blood values
Sodium: 130 mEq/L (range, 142–150)
Potassium: 3.8 mEq/L (range, 3.4–4.9)
Glucose: 101 mg/dL (range, 60–115)
Hematocrit: 27% (range, 35–50)
pH: 7.336 (range, 7.35–7.45)
Ionized calcium: 1.06 mmol/L (range, 1.12–1.4)
9:00 AM blood values
Sodium: 129 mEq/L (range, 142–150)
Potassium: 3.8 mEq/L (range, 3.4–4.9)
Chloride: 100 mEq/L (range, 106–127)
Glucose: 114 mg/dL (range, 60–115)
Blood urea nitrogen: <3 mg/dL (range, 10–26)
Hematocrit: 28% (range, 35–50)
pH: 7.37 (range, 7.35–7.45)
Treatment:
Medications
Ampicillin (20 mg q8h IV)
Dolasetron (0.5 mg q24h IV)
Enrofloxacin (8 mg q24h IV)
Metronidazole (8 mg q12h IV)
Famotidine (0.4 mg q24h IV)
Maropitant (0.3 mg q24h SC)
Metoclopramide (1 mg/kg/d at 2 mL/hr CRI)
Hetastarch: (0.6 mL/h IV)
Fluids
Plasmalyte (3 mL/hr) + 2.5% dextrose and 20 mEq/L potassium chloride IV. Changed IV fluids to 0.9% sodium chloride + 2.5% dextrose and 30 mEq/L potassium chloride at 6:00 PM.
Syringe fed throughout the day.
Day 4
3:00 AM: Puppy was weak and ataxic.
Glucose: 21 mg/dL (range, 60-115)
Administered 0.8 mL bolus of 25% dextrose; increased dextrose CRI to 5%.
6:00 AM blood values
White cells: 400/μL (range, 6,000–17,000)
Lymphocytes: 300/μL (range, 900–5,000)
Platelets: 88/μL (range, 200,000–500,000)
Glucose: 40 mg/dL (range, 60–115)
Packed cell volume/total protein: 23%/3.2 g/dL (ranges, 36–60/5.0–7.4)
8:00 AM: Puppy was dull and weak.
Temperature: 97.6⁰F
Heart rate: 160 bpm
Blood pressure: 90 bpm
Blood values
Sodium: 137 mEq/L (range, 142–150)
Potassium: 2.0 mEq/L (range, 3.4–4.9)
Chloride: 102 mEq/L (range, 106–127)
Glucose: <20 mg/dL (range, 60–115)
Blood urea nitrogen: 6 mg/dL (range, 10–26)
Hematocrit: 19% (range, 35–50)
pH: 7.389 (range, 7.35–7.45)
Administered 1 mL 25% dextrose bolus; increased dextrose CRI to 7.5% and potassium chloride supplementation to 60 mEq/L––all IV.
11:00 AM treatment
Hyperimmune plasma (3rd transfusion; 8 mL DEA negative over 2 hours)
Additional bolus of dextrose after completing transfusion
Started partial parenteral nutrition, at 70% of puppy’s resting energy requirement
4:00 PM blood values
Sodium: 133 mEq/L (range, 142–150)
Potassium: 2.2 mEq/L (range, 3.4–4.9)
Chloride: 105 mEq/L (range, 106–127)
Glucose: 28 mg/dL (range, 60–115)
Blood urea nitrogen: 5 mg/dL (range, 10–26)
Hematocrit: 20% (range, 35–50)
pH: 7.492 (range, 7.35–7.45)
Administered fresh frozen plasma (4th transfusion; 8 mL DEA positive over 2 hours). Posttransfusion blood glucose: 32 mg/dL
Treatment throughout day:
Medications
Ampicillin (20 mg q8h IV)
Enrofloxacin (8 mg q24h IV)
Metronidazole (8 mg q12h IV)
Famotidine (0.8 mg q24h IV)
Dolasetron (0.5 mg q24h SC)
Metoclopramide (2 mg/kg/d IV CRI)
Fluids
Sodium chloride (0.9%; 3 mL/hr) + 7.5% dextrose and 60 mEq/L potassium chloride IV
Hetastarch: (0.6 mL/hr IV)
Nutrition
Partial parenteral nutrition (4 mL/hr IV)
Day 5
8:00 AM: Puppy was quiet, alert, responsive; brighter and stronger. Blood glucose was normal; there had been continued regurgitation and diarrhea overnight.
Blood Values
Sodium: 132 mEq/L (range, 142–150)
Potassium: 3.4 mEq/L (range, 3.4–4.9)
Chloride: 101 mEq/L (range, 106–127)
Gucose: 99 mg/dL (range 60–115)
Blood urea nitrogen: 10 mg/dL (range, 10–26)
Hematocrit: 15% (range, 35–50)
Packed cell volume/total solids: 19%/2.6 (ranges, 36–60/5.0–7.4)
pH: 7.316 (range, 7.35–7.45)
Decreased potassium chloride supplementation to 40 mEq/L; decreased dextrose CRI to 5% IV.
Treatment throughout the day:
Medications
Ampicillin (20 mg q8h IV)
Enrofloxacin (8 mg q24h IV)
Metronidazole (8 mg q12h IV)
Famotidine (0.4 mg q24h IV)
Day 6
8:00 AM: Puppy had clear regurgitation and began to appear icteric throughout the day; tolerated syringe feedings. Temperature and blood pressure were normal.
Increased potassium chloride supplementation to 60 mEq/L; dextrose CRI decreased to 2.5%; partial parenteral nutrition decreased and then discontinued (due to concern for causing fluid shift and contributing to hyponatremia); saline CRI increased to 3 mL/hr. Laboratory work showed a low osmolality of 265.
Blood values
Sodium: 127 mEq/L (range, 142–150)
Potassium: 2.5 mEq/L (range, 3.4–4.9)
Chloride: 90 mEq/Ll (range, 106–127)
Glucose: 23 mg/dL (range, 60–115)
Blood urea nitrogen: 11 mg/dL (range, 10–26)
Hematocrit: 13% (range, 35–50)
Packed cell volume/total solids: 14%/2.6 g/dL (range, 36–6-/5.0–7.4)
pH: 7.544 (range, 7.35–7.45)
Administered packed red blood cells (5th transfusion) 6 mL DEA negative over 3 hours. Due to continued hypoglycemia despite dextrose boluses, dextrose CRI was maintained at 5% and continued during the transfusion.
8:00 PM blood values
Sodium: 129 mEq/L (range, 142–150)
Potassium: 2.4 mEq/L (range, 3.4–4.9)
Chloride: 94 mEq/L (range, 106–127)
Glucose: 49 mg/dL (range, 60–115)
Blood urea nitrogen: 16 mg/dL (range, 10–26)
Hematocrit: 11% (range, 35–50)
Packed cell volume/total solids: 12%/3 g/dL (ranges, 36–60/5.0–7.4)
pH: 7.64 (range, 7.35–7.45)
Total bilirubin: 3.6 mg/dL (range, 0–0.8)
Treatment throughout the day:
Medications
Ampicillin (20 mg q8h IV)
Enrofloxacin (8 mg q24h IV)
Metronidazole (8 mg q12h IV)
Famotidine (0.4 mg q24h IV)
Maropitant (0.3 mg q24h SC)
Metoclopramide (2 mg/kg/d at 2 mL/hr)
Fluids
0.9% sodium chloride (3 mL/hr) + dextrose and 60 mEq/L potassium chloride) IV
Hetastarch (0.5 mL/h IV)
Nutrition
Partial parenteral nutrition (4 mL/hr)
CLINICAL OUTCOME
The second transfusion of packed red blood cells had been planned for the morning of day 7, but the puppy was unable to maintain normoglycemia on 7.5% dextrose (could not discontinue to start transfusion). Attempted to place second catheter; prolonged clotting was noted. Catheter was placed uneventfully. While checking blood pressure, full cardiopulmonary arrest occurred. Immediately after the arrest, a complete blood count showed marked derangements:
White cells: 1,200/μL (range, 6,000–17,000)
Lymphocytes: 600/μL (range, 900–5,000)
Platelets: 9,000/μl (range, 200,000–500,000)
Packed cell volume/total solids: 10%/2.8 g/dL (ranges, 36–60/5.0–7.4)
Prothrombin time: 11 sec (range, 7–12.7), partial thromboplastin time: 91 sec (range, 10–28)
Euthanasia was performed due to the grim prognosis.
The Generalist’s OpinionBarak Benaryeh, DVM, DABVPIt’s difficult to find areas for improvement in the treatment regimen for this puppy. Many dogs recover from parvovirus infection, but there are those that, despite aggressive treatment, will not survive. Any conversation and cost estimate for owners has to include the possibility of an outcome such as this unfortunate one.
Early DiagnosisThe dog was diagnosed on the second visit, as a parvovirus test was not performed at the initial examination. Two issues arise with this omission: First, the treatment was delayed. The delay may not have made any difference in the final outcome, but earlier intervention may have helped. Second, any areas of the veterinary clinic in which the puppy spent time may not have been properly disinfected, leaving others dogs susceptible. An in-house parvovirus test is quick and inexpensive. Any index of suspicion, no matter how small, merits a test. Be sure to check the date of the last parvovirus vaccine, as a recent vaccination can interfere with results. Clinical signs and associated leukopenia will help confirm the diagnosis if there is any doubt.
Antibiotic ChoicesThe antibiotic choices were ampicillin on day 1, followed by the addition of metronidazole and enrofloxacin on day 2. Antibiotics are needed in parvovirus infection because of an ensuing breakdown in the gastrointestinal mucosal barrier that leads to bacterial translocation and related complications. If the white blood cell count is low (such as in this case) and the dog is showing severe clinical signs, aggressive antibiotic therapy should be instituted. Combination therapy with ampicillin, enrofloxacin, and metronidazole is a good choice. An alternative, provided the dog has been hydrated, is the combined use of ampicillin and gentamycin. Ideally the aggressive antibiotic regimen should start on day 1.
Concurrent Parasite BurdenOne possible oversight in this case was the absence of a fecal examination by zinc centrifugation. Presence of intestinal parasites has been identified as a factor that can exacerbate viral gastrointestinal disease. Many parvovirus-infected puppies have hookworm coinfection. Even with a negative fecal, consideration should be given to prophylactic deworming.
Antiviral TherapyAlthough oseltamivir (Tamiflu) was not used in this case, it is worth discussing, as some sources still recommend use of this drug early in the disease. Oseltamivir has been shown to be of no benefit in parvovirus infected dogs: It is a neuraminidase inhibitor and parvovirus does not use neuraminidase.
In conclusion, this case exemplifies an appropriate way to treat severe parvovirus infection. The areas of subtle improvement that could have been made were quicker identification of the disease, more aggressive antibiotic therapy on day 1, a fecal examination, and prophylactic deworming. What is most notable in this case is just how difficult and heartbreaking some of these cases can be.
Barak Benaryeh, DVM, DABVP, is the owner of Spicewood Springs Animal Hospital. He graduated from University of California–Davis School of Veterinary Medicine in 1997 and completed an internship in Small Animal Medicine, Surgery, and Emergency at University of Pennsylvania. Dr. Benaryeh has also taught practical coursework to first-year veterinary students and was a primary veterinary surgeon for the Helping Hands Program, which trains assistance monkeys for quadriplegic people. Dr. Benaryeh is certified by the American Board of Veterinary Practitioners in Canine and Feline Practice.
The Specialist’s OpinionGretchen Statz, DVM, DACVECC
Parvoviral enteritis can be difficult to treat. The prognosis is variable, with some puppies showing only mild clinical signs while others are severely affected. Death can occur rapidly, usually secondary to sepsis or disseminated intravascular coagulation (DIC). The outcome of this case is unfortunate but not completely unexpected given the severity of illness. In general, I think the treatment covered all of the typical categories recommended for parvovirus infections (ie, antiemetics, antimicrobials, gastric protectants, fluid therapy, transfusion therapy, pain medication, and nutritional support). Here are some specific thoughts.
Treatment of Hypoglycemia & HypokalemiaHypoglycemia and hypokalemia are both very common findings in puppies with parvoviral enteritis. In this case the derangements were severe and relatively persistent despite aggressive treatment. The hypoglycemia was treated with appropriate therapy including intermittent boluses of dextrose and continuous rate infusions (CRI) up to 7.5%. However, the monitoring of glucose could have been more frequent. An example would be on day 4, when glucose was checked at 8 AM and found to be <20 mg/dL and then not checked again until 4 PM, when it was still extremely low (28 mg/dL).
Similarly, the dextrose CRI was discontinued to allow for the various transfusions, whereupon the glucose was low after at least one of the transfusions (day 4). It would have been ideal to place a second catheter earlier in the course of therapy (intravenous or intraosseous) to allow for continued fluid, dextrose, and electrolyte therapy during transfusion therapy. Dextrose infusions above 7% should be given through a central line to avoid thrombophlebitis.
The hypokalemia was also severe and difficult to treat. A CRI is a more aggressive alternative for bringing the potassium up more quickly; using a syringe pump, it can be given at a maximum of 0.5 mEq/kg/hr (taking into account the potassium present in the IV fluids) diluted with saline over 4 to 6 hours. This method, while helpful in cases of severe hypokalemia, must be performed by qualified nursing staff with close monitoring. In cases in which a CRI cannot be performed, aggressive supplementation through the IV fluids can provide an alternative, which was the approach taken in this case. The potassium did respond on day 3 but dropped again on day 4. Hypomagnesemia can be a cause of persistent or refractory hypokalemia. Measurement of ionized magnesium may have been beneficial.
Nutritional SupportNutritional support is an important part of therapy for parvoviral enteritis. One study showed that puppies treated earlier with enteral nutrition had better outcomes.1 Puppies were fed via syringe on day 3 and switched to partial parenteral nutrition on day 4. Although some animals do tolerate syringe feeding well, it can be difficult to maintain caloric requirements and food aversion can occur (more so in cats). Parenteral nutrition (PN) avoids these issues; however, PN does not provide nutrition to the gastrointestinal (GI) tract which is important to maintain integrity of the gut mucosal barrier and to prevent bacterial translocation. A nasoesophageal (NE) tube placed early in treatment may have been a better choice. NE tubes are well tolerated and allow for trickle feeding by CRI, thereby often preventing regurgitation or vomiting.
Fluid TherapyThe fluid rates were not mentioned on all of the treatment days; however, those mentioned on days 2 and 3 (5 mL and 3 mL/hr, respectively) seem low: Dogs with parvoviral enteritis often require aggressive fluid resuscitation due to large fluid losses through the GI tract, and pediatric patients require higher maintenance fluid rates than adult dogs (80–100 mL/kg/day). A maintenance rate in this case would have been approximately 3 mL/hr; however, that does not provide for correction of hypovolemia and dehydration and replacement of ongoing losses. Pediatric patients with diarrhea and vomiting should be assumed to have some degree of fluid deficit, so rates above maintenance are indicated. It can be difficult to assess pediatric patients for deficits (hypovolemia and dehydration) and for fluid overload. Frequent monitoring of body weight (along with other parameters) in these tiny patients can be helpful for determining hydration status.
Hypoalbuminenia is a common finding in puppies with parvoviral enteritis. Albumin less than ~1.6 g/dL can result in decreased oncotic pressure, which can lead to fluid shifts out of the vascular space and ensuing edema. Hetastarch (HES) is often started in puppies with parvoviral enteritis when the albumin drops below 2.0 g/dL. The albumin in this case was reported as low (1.7 g/dL) on day 2 but HES was not mentioned until day 4. Adding HES earlier may have helped to maintain oncotic pressure and therefore intravascular volume.
Transfusion TherapyHyperimmune plasma has been reported to improve survival and decrease clinical signs in experimental cases of parvovirus. The puppy in this case was treated with 3 separate transfusions of hyperimmune plasma. This was a reasonable treatment given the severity of the case; however, I am not certain that repeat dosing has any advantage over a single transfusion. A lecture presented at the International Veterinary Emergency and Critical Care Symposium in 2011 discussed a study that failed to show any clinical differences in patients receiving hyperimmune plasma, and there was no difference in level of viremia between those that did and did not receive these transfusions.2
Fresh frozen plasma transfusions are sometimes used to provide albumin, immunoglobulin, and clotting factors. To my knowledge, there are no studies that show that plasma transfusions improve survival or hasten recovery in puppies with parvovirus infection. Plasma transfusions are indicated to help treat hypocoagulability associated with DIC. The platelet count did drop in this case, which may have been related to consumption (GI blood loss) or impending DIC. Thus, assessing coagulation factors was warranted.
Red blood cell transfusions are sometimes necessary in dogs with parvoviral enteritis due to significant GI hemorrhage and/or DIC. A packed red blood cell transfusion was provided to the puppy in this case. It could be argued that the transfusion should have been given on day 5 (when the hematocrit dropped to 15%) instead of day 6.
Gretchen Statz, DVM, DACVECC, is an internal medicine consultant for Antech Diagnostics and a VIN consultant on the internal medicine boards. A graduate of University of Wisconsin – Madison, Dr. Statz interned at VCA West Los Angeles and then worked for several years at two emergency/referral hospitals in the Boston area. After completing a residency at VCA Veterinary Referral Associates in Gaithersburg, Maryland, she became boarded in emergency and critical care. Having a strong interest in internal medicine, she has been practicing in that field for the past several years.
References
1) Effect of early enteral nutrition on intestinal permeability, intestinal protein loss, and outcome in dogs with severe parvoviral enteritis. Mohr AJ, Leisewitz AL, Jacobson LS. J Vet Intern Med 17:791-798, 2003.2) Parvoviral enteritis: It's more complicated these days! Hackett T. Proc Int Vet Emerg Crit Care Symp, 2011.