• GI condition
  • Abdominal pain (eg, from visceral stretching)
  • Disease associated with nausea
  • Esophageal disease (eg, reflux esophagitis, megaesophagus, foreign body, neoplasia, stricture, spirocercosis)
  • Gastric dilatation volvulus
  • Gastric ulceration
  • Hepatic failure (eg, hepatic encephalopathy), particularly in cats
  • Hiatal hernia
  • Renal failure
• Idiopathic or nonresponsive condition
• Neurologic condition
  • Facial nerve paralysis
  • Idiopathic trigeminal neuritis
  • Infectious disease (eg, rabies,^† pseudorabies, tetanus, botulism)
  • Lesions of cranial nerves IX, X, or XII
  • Myasthenia gravis
  • Nausea from vestibular disease
  • Seizures
• Oral cavity or maxillofacial cause
  • Craniomandibular osteopathy
  • Faucitis
  • Foreign body
  • Immune-mediated disease (eg, masticatory muscle myositis, pemphigus)
  • Lip fold abnormalities
  • Mandibular fracture
  • Oropharyngeal neoplasia (eg, tonsillar squamous cell carcinoma)
  • Oropharyngeal trauma (eg, laceration)
  • Periodontal disease
  • Stomatitis (eg, calicivirus, herpesvirus, FeLV/FIV, caustic agent, electrical burn, ulceration secondary to systemic disease [eg, uremia])
  • Temporomandibular joint luxation or fracture
  • Tongue lesion (eg, linear foreign body), glossitis (eg, uremia, caustic agent, electrical burn), or tumor
• Physiologic reaction
  • Excitement
  • Hyperthermia
  • Purring
  • Response to feeding
• Reaction to medication
  • Anesthesia
  • Avermectins (eg, ivermectin, moxidectin/imidacloprid, selamectin) given topically or PO
  • Bitter drugs
  • Cholinergic drugs (eg, bethanechol), anticholinesterase drugs (eg, pyridostigmine), cholinesterase inhibitors (eg, organophosphates)
  • Pancreatic enzyme supplements
  • Pyrethrins/pyrethroids
• Salivary gland condition
  • Foreign body
  • Salivary gland neoplasia
  • Salivary mucocele
  • Sialadenitis or necrotizing sialometaplasia (ie, inflammation of the salivary glands)
  • Sialadenosis (idiopathic, noninflammatory salivary gland enlargement)
    • May be a form of limbic epilepsy 
  • Sialolithiasis
• Sepsis
• Toxicosis
  • 5-hydroxytryptophan (ie, Griffonia seed extract)
  • Bite from a venomous animal (eg, black widow spider, scorpion, toad [Bufo spp], coral snake, sea hare [Aplysia spp])
  • Household cleaner 
  • Human sleep aid (eg, zolpidem)
  • Human tricyclic antidepressant (eg, clozapine)
  • Illicit drug (eg, cocaine, amphetamine)
  • Insecticide/pesticide (eg, boric acid, aldicarb)
  • Metaldehyde
  • Mushroom (eg, Amanita muscaria)
  • Plant/tree (eg, Kentucky coffee tree, poinsettia)
  • Rodenticide (eg, zinc phosphide)

The canine hookworm (Ancylostoma caninum) is the most common and highly pathogenic nematode parasite in dogs.¹ This parasite uses 3 pairs of teeth to attach to the intestinal mucosa and submucosa to feed on host blood. Clinical signs of infection include hematochezia, melena, anemia, and weight loss; heavy worm burdens can cause death (Figure 1).

Research conducted at the Kaplan Laboratory at University of Georgia has led to several key discoveries relating to anthelmintic resistance in A caninum:

Research conducted in the authors’ laboratory over the past 2 years has confirmed that A caninum has developed multiple-anthelmintic resistance to the major anthelmintic classes commonly used for treatment: benzimidazoles (eg, fenbendazole, febantel), tetrahydropyrimidines (eg, pyrantel pamoate), and macrocyclic lactones (eg, milbemycin oxime, moxidectin)²; selected data from these studies are presented in Figure 2.

Anthelmintic resistance is defined as a heritable genetic change in a parasite population that enables a significantly greater proportion of individual parasites to survive treatment at a dose that was previously effective against the same species and developmental stage. Strongylid nematode parasites have extremely large effective population sizes that yield exceptionally high levels of genetic diversity that favor the development of anthelmintic resistance.^3,4 This has led to long-standing severe resistance problems in GI nematode parasites in livestock; however, few reports have documented such anthelmintic resistance in dogs. The first report of anthelmintic resistance in A caninum was to pyrantel pamoate in 1987 in a greyhound puppy imported from Australia.⁵ Additional pyrantel pamoate resistance cases were subsequently diagnosed in Australia.^6,7 However, since 2008, there had been no further published reports of anthelmintic resistance in A caninum to any drug until 2019.

Evidence recently collected by the Kaplan Laboratory strongly suggests that multiple-drug–resistant (MDR) A caninum evolved on greyhound breeding farms and racing kennels, and most, if not all, actively racing and recently adopted greyhound dogs appear to be infected with these MDR hookworms.

The development of MDR A caninum is most likely the result of a combination of long-term intensive use of anthelmintics and the epidemiologic dynamics that exist on greyhound breeding farms. A caninum is extremely common on greyhound breeding farms, likely due to an ideal environment for larval development and transmission conferred by sand and dirt exercise runs.⁸ This results in intensive anthelmintic use, which over several decades has likely resulted in heavy selection pressures for drug resistance leading to the development of MDR parasites. The adoption of thousands of retired racing greyhounds each year has likely led to the spread of these MDR parasites to the general pet population. However, to date, there are no data on the prevalence or distribution of MDR hookworms in the pet population. The authors are currently investigating the geographic distribution and the molecular epidemiology of A caninum drug resistance.

MDR hookworms are not restricted to greyhounds; the authors have observed many cases of drug-resistant hookworms in nongreyhound breeds, suggesting that MDR hookworms are spreading to the general canine population. The emergence and spread of MDR hookworms that are poorly responsive to usual anthelmintic treatments present a serious threat to canine health and necessitate a change in how clinicians manage persistent hookworm cases. In addition, due to its zoonotic potential, the spread of MDR A caninum is also a threat to human health.

Persistent cases of A caninum infection can be caused by either larval leak (ie, arrested larvae in somatic tissues continuously migrate to the small intestine, where they develop to the adult stage⁹) or true drug resistance; it is important to distinguish between these situations to optimally manage each patient. Dogs with larval leak typically shed hookworm eggs in small numbers, with treatment only yielding a temporary interruption in egg shedding due to newly reactivated larvae repopulating the gut. In contrast, when worms are MDR, treatments fail to interrupt egg shedding. Performing both pretreatment and 14-day post-treatment fecal egg counts is required to make this distinction. 

All resistant A caninum isolates that the authors have tested to date have been MDR to all 3 drug classes mentioned previously. However, it is possible that some A caninum isolates are only resistant to 1 or 2 drug classes. Of note, resistance is not an “all or none” phenomenon; resistance levels differ depending on recent treatment history of the dog(s) transmitting and carrying resistant hookworms.

The only practical method to diagnose anthelmintic resistance in A caninum is the fecal egg count reduction test, in which the number of worm eggs per gram of feces is measured both prior to and 2 weeks after treatment. Most large animal clinicians are familiar with this test, as testing for anthelmintic resistance on livestock farms has long been recommended. Due to the emergence of MDR hookworms in dogs, small animal clinicians should also become familiar with this test, which should be performed in any dog that has persistent hookworms.

Recommendations for performing this test and interpreting the results will be presented by the authors in a diagnostic, treatment, and management algorithm for resistant canine hookworm infections in an upcoming issue of Clinician’s Brief. This algorithm will also provide recommendations for short- and long-term case management.

Aaron, a 15-year-old neutered male, domestic shorthair  cat, was presented to his veterinarian for a proactive senior wellness examination. He had a history of being a picky eater and vomiting on a monthly basis. On examination, Aaron weighed 12.3 lb (5.6 kg) and had a BCS of 4/5, slightly tacky mucous membranes, and stage 2 of 4 periodontal disease. Physical examination was otherwise unremarkable.

Systolic blood pressure was elevated (>150 mm Hg), and blood work revealed azotemia (creatinine, 2.7 mg/dL [range, 0.9-2.5 mg/dL]; BUN, 50 mg/dL [range, 16-37 mg/dL]) with a mildly elevated symmetric dimethylarginine (16 ug/dL [range, 0-14 ug/dL]). Urine was dilute, with a urine specific gravity of 1.016 and a quiet sediment; a urine protein:creatinine ratio was declined by the owners.

Aaron was diagnosed with International Renal Interest Society (IRIS) stage 2 CKD and was started on Hill’s Prescription Diet k/d Feline. The owners were advised to slowly transition Aaron’s food and to offer several Prescription Diet k/d options so that Aaron could choose his favorite. The owners were sent home with a Prescription Diet k/d starter kit containing a variety of k/d flavors and food textures (eg, dry, minced, stew).

Aaron’s owners reported during a follow-up phone call 2 days later that Aaron refused the minced food but was eating both the dry and stew formulations well. A recheck examination 2 months later revealed maintenance of normal lean muscle mass and improvement in azotemia.

Through proper feeding practices, Aaron was able to chronically maintain his weight and LBM, which are crucial components of an effective renal food. However, the ability of renal foods to maintain LBM has recently come under question.^2,3 Although renal foods have many important features (eg, reduced phosphorus and sodium; increased caloric density; supplementation with potassium, B vitamins, antioxidants, and omega-3 fatty acids),¹ their controlled level of protein is receiving attention due to its effects on LBM.^2-4

One school of thought advocates against protein restriction, as it may lead to decreased LBM,^2,3,5  a concerning effect in light of the fact that significant reduction in LBM has been associated with increased mortality in cats with CKD.² A second school of thought, however, advocates for protein restriction to reduce uremic signs caused by an accumulation of protein metabolites, which are excreted by the kidneys.^1,2,4 In addition, protein is a significant source of dietary phosphorous, and controlling intake levels of protein can help limit phosphorous intake.²

To promote patient comfort and longevity, effective renal foods should contain controlled but adequate levels of protein to support LBM.

Hill’s Prescription Diet k/d Feline overcomes these challenges with innovative dietary solutions. The protein in Prescription Diet k/d is highly digestible and contains high levels of essential amino acids to maintain LBM. In addition, it contains high levels of L-carnitine and omega-3 fatty acids.⁶ Therefore, Prescription Diet k/d Feline is not protein-restricted, as it provides adequate protein building blocks to support LBM maintenance while preserving low phosphorus levels.

In a recent, prospective clinical study, cats with IRIS stage 1 or 2 CKD were fed either Prescription Diet k/d Feline or a different therapeutic renal food for 6 months.⁷ Cats fed Prescription Diet k/d experienced no change in their LBM over the course of the study and also experienced a significant increase in body weight, whereas cats fed the alternate therapeutic food lost weight and had reduced LBM. Comparatively, cats fed Prescription Diet k/d consumed 23% more calories than cats fed the alternate food.

The above study demonstrates that cats fed Hill’s k/d can maintain LBM and increase their body weight while on a therapeutic renal food.⁷ Sufficient caloric intake is critical for cats with CKD to prevent muscle tissue from being used for energy. Specifically formulated for feline patients with CKD, Prescription Diet k/d supports optimal caloric intake through proper formulation of balanced nutrients to calories.

Prescription Diet k/d has a demonstrated track record of palatability.^7-9 Its proprietary Enhanced Appetite Trigger (EAT) Technology stimulates appetite, increasing caloric intake.⁶ It has been shown that 94% of cats successfully transition  to Prescription Diet k/d dry food when receiving a proper transition period.⁸

Even with appropriate transitions, however, some cats may be finicky, disliking certain flavors or textures, an effect that can be exacerbated by their disease.¹ As Aaron’s case demonstrates, meeting patient preferences with regard to flavor and texture can be crucial for feeding success. To address this, Hill’s offers k/d in dry, minced, and stew textures in several flavors, with all these varieties available as part of their Prescription Diet k/d starter kits.

CKD is a complex disease in which many nutritional factors and patient preferences must be balanced to achieve optimal management. Hill’s Prescription Diet k/d Feline combines science with an understanding of feline behavior to maintain LBM, provide an ideal nutrient profile, and boost palatability, helping cats combat CKD and live longer, more comfortable lives.

Learn more about Hill's Prescription Diet k/d at HillsVet.com/Renal

Intussusception refers to invagination of a portion of the GI tract into the lumen of an adjacent segment. It is sometimes overlooked as a potential cause of GI clinical signs in presenting patients. The 2 components of intussusception include the invaginated section (ie, the intussusceptum) and the adjoining segment that holds the intussusceptum (ie, the intussuscipiens).¹ Underlying disease processes can alter gut motility, resulting in intussusception.² Many cases of intussusception are idiopathic and intermittent; thus, diagnosis and treatment of the underlying cause are difficult. Causes of intussusception may include neoplasia, intestinal parasites, viral enteritis, foreign body obstruction, or cecal inversion^2,3; previous abdominal surgery is a risk factor.

Intussusception can occur at any age but is most commonly recognized in patients younger than 1 year¹ and therefore should be included among the differential diagnoses for any juvenile patient presented with GI signs. Intussusception most commonly occurs at the ileocecocolic junction but can occur along any portion of the GI tract, including the stomach and esophagus.¹ Clinical signs at the time of presentation are typically related to the location of intussusception.

Diagnostic steps include a complete physical examination, abdominal radiography, and abdominal ultrasonography (or a contrast study if ultrasonography equipment is not available). On physical examination, a thickened tubular structure may be palpated in the abdomen, which may be painful for the patient. Abdominal radiographs commonly reveal a fluid- or gas-filled bowel consistent with a mechanical obstruction.² Abdominal ultrasonography is often the most helpful preoperative diagnostic tool (Figure 1); the finding of multiple hyperechoic and hypoechoic concentric rings in transverse sections, parallel lines in longitudinal sections, or both is diagnostic of intestinal intussusception.⁴ Abdominal radiography with contrast media (ie, barium) can outline the intussusceptum in the lumen of the intussuscipiens, or the contrast can appear as a ribbon-like structure in the intussusceptum.²

Treatment of intestinal intussusception involves laparotomy with manual reduction if the affected segment appears potentially viable and/or resection and anastomosis of the affected intestinal segment if neoplasia is the underlying cause or if the affected segment is necrotic or cannot be reduced (Figures 2-4).

Intussusception recurrence rates are ≈6% to 27%, and recurrence is usually observed 3 days to 3 weeks postsurgery.¹ Recurrence typically affects the segment immediately proximal to the previous intussusception site.² Enteroplication reduces the risk for intussusception recurrence by creating permanent adhesions between adjacent loops of intestine. Enteroplication is completed by preparing the intestines using manual reduction or resection and anastomosis of compromised bowel. After the intestines have been prepared, adjoining segments should be placed side by side in a zigzag pattern with care not to create kinks or sharp bends. The adjacent loops should be sutured together with either absorbable or nonabsorbable suture and should penetrate the submucosal layer midway between the mesenteric and antimesenteric borders to ensure a secure hold. Complete plication encompasses plication of the jejunum to the ileum; the duodenum should not be included because it is rarely involved with intussusception.³

Enteroplication can be performed immediately after reduction if the affected segment appears viable and without obvious pathology; however, enteroplication should only be performed in select cases (eg, spontaneous reduction intussusception in young dogs, presence of hyperperistalsis during surgery, cases involving multiple or recurrent intussusception)³ because of the risk for complications. The procedure has been associated with abdominal discomfort, vomiting/diarrhea, hyporexia, constipation, increased risk for future obstructions, bowel strangulation, and intra-abdominal abscess formation.³

Intussusception involving the stomach is rare and requires a different treatment approach. For example, patients with gastroesophageal intussusception should be treated with left (± right) incisional gastropexy and may require sutures to reduce the size of the esophageal hiatus.⁵ A partial gastrectomy or Y-U pyloroplasty (ie, a procedure in which the pyloric antrum is advanced aborally) should be considered after reduction of gastroduodenal intussusception.⁶

For most idiopathic cases of intussusception, the long-term prognosis is good with appropriate aftercare and treatment, but prognosis ultimately depends on the specific underlying cause. In cases for which a diagnosis is not grossly apparent, samples of the area of intussusception, as well as samples of other areas of intestine, can be submitted for biopsy.⁷ Because intestinal parasitism is also a potential predisposing factor for intussusception, fecal samples can also be collected preoperatively for testing and empiric deworming can be performed in case of false negatives.²

• Basic surgery pack
  • Hemostats
  • DeBakey forceps
  • Scalpel handle
  • Needle drivers
  • Suture scissors
  • Metzenbaum scissors
  • Mayo scissors
  • Poole suction
  • Radiopaque gauze and laparotomy sponges
• Balfour retractor
• 3-0 or 4-0 absorbable monofilament suture
• #11 or #15 scalpel blades

Additional instruments that may be helpful:

• Doyen forceps
• Vessel sealant device
• Electrocautery
• GI anastomosis stapler
• Thoracoabdominal stapler

Clip, clean, and perform sterile preparation of the abdomen.

Using a standard ventral midline approach, begin abdominal exploratory surgery. Line the abdominal incision with 2 dampened laparotomy sponges along the linea alba. Place a Balfour retractor to allow appropriate visualization into the abdomen.

Examine the entire GI tract for abnormalities; multiple occurrences of intussusception may be present.

Isolate the area of intussusception and pack off the region with dampened laparotomy sponges.

Attempt manual reduction via gentle manipulation. If the intussusception is easily reduced and the affected segment appears viable, complete the exploratory surgery and close the incision in a standard fashion.

If the intussusception does not easily reduce or is associated with an intestinal mass, or if the affected segment is nonviable, perform resection and anastomosis (see Steps 6-10).

Gently milk intestinal contents away from the portion of intestine that will be resected. Use digital compression or Doyen forceps to gently seal the oral and aboral portions to reduce contamination. Occlude the lumen orad and aborad to the site of resection with gloved and sterile fingers.

Isolate the blood supply of the affected bowel segment and ligate appropriately.

Sharply excise the affected intestinal tract and discard or place aside for histopathology. Be careful to avoid contamination of the surgical field.

Perform either end-to-end anastomosis with absorbable or nonabsorbable sutures or side-to-side anastomosis with surgical and thoracoabdominal staplers.

Achieve adequate intestinal closure, then lavage the peritoneal cavity with sterile saline, suture the omentum to the anastomosis site, and close the incision in a standard fashion.

Several species of blue-green algae are capable of producing toxins. Cyanotoxins commonly associated with freshwater algal blooms include microcystins/nodularins (hepatotoxic), cylindrospermopsin (hepatotoxic), anatoxin-a/anatoxin-a(s) (neurotoxic), and saxitoxins (ie, paralytic shellfish poison; neurotoxic). Microcystins and anatoxin-a/anatoxin-a(s) are the most common cyanotoxins in North America and occur across the country. Cyanotoxins can affect any species. The following discussion focuses on the effects of microcystins and anatoxin-a/anatoxin-a(s) on dogs.

Microcystins are cyclic heptapeptides that inhibit serine threonine protein phosphatases and lead to reorganization of hepatocyte infrastructure and eventual hepatocyte apoptosis.^3,4 Microcystins are transported into cells by organic anion transport proteins, which are highly expressed in hepatocytes in relation to other cell types.^5,6 Increased production of necessary transport proteins in hepatocytes can explain the propensity for microcystins to target the liver following ingestion; this could also be because the liver is the first organ exposed to ingested toxins absorbed from the GI tract. There are reports of microcystin intoxication causing lesions in the kidney.^7,8

Anatoxin-a is a bicyclic amine alkaloid that is a potent acetylcholine-receptor agonist and exhibits greater affinity for nicotinic receptors than for muscarinic receptors.^2,9 Anatoxin-a(s) is a guanidine methyl phosphate ester that is a naturally occurring organophosphate and potent inhibitor of acetylcholinesterase.^10,11

Although predicting the occurrence of algal blooms can be challenging, common environmental conditions exist, including warm (>70°F [21°C]), stagnant waters with some mechanism of nutrient accumulation. Nitrogen and phosphorus are the main nutrients implicated in eutrophication (ie, abnormal accumulation of nutrients, commonly due to surface runoff), which leads to harmful algal blooms that often appear as a thick scum, similar to paint, on the surface of a body of water.¹² Nitrogen and phosphorus can enter bodies of water from many sources (eg, fossil fuel combustion; stormwater discharge; groundwater pollution; agricultural and residential fertilizers; urban, industrial, and agricultural waste).¹³ Cyanotoxin poisonings typically occur in late summer or early fall, as water temperatures rise and rainfall tapers off.

Patients with cyanotoxin poisoning have an acute onset of clinical signs following exposure to a suspect water source and are often in critical condition or deceased when presented to the clinic. Patients with microcystin poisoning show clinical signs within hours of exposure, and death can occur within 24 hours. Patients with anatoxin-a/anatoxin-a(s) poisoning show almost immediate clinical signs, and death can occur <1 hour after exposure. Algal blooms often produce odors attractive to dogs, leading them to play in the water and ingest the algae-created surface scum; this behavior may play a role in the susceptibility of dogs to cyanotoxin poisoning.¹⁴

Clinical signs related to microcystin exposure initially reflect GI insult, particularly vomiting, abdominal pain, and bloody diarrhea. The severity of clinical signs worsens with liver damage and developing coagulopathy. Lethargy, weakness, pallor, seizures, and death can follow. Patients that do not succumb to initial GI and acute liver toxic insult may have chronically impaired liver function. The amount of microcystins ingested and the patient’s ability to metabolize microcystins (via glutathione-S-transferase pathway) are the most important factors impacting the severity of clinical signs and the degree to which the patient is affected.¹⁵

Clinical signs associated with anatoxin-a exposure are similar to succinylcholine overdose, with muscle rigidity, tremors, seizures, paralysis, cyanosis, and death likely due to respiratory paralysis.⁹ Anatoxin-a(s) inhibits acetylcholinesterase; clinical signs include SLUD (ie, salivation, lacrimation, urination, defecation) syndrome as well as signs associated with anatoxin-a exposure.

Cyanotoxin poisoning can mimic a variety of diseases due to the different mechanisms of action of different toxins. Differential diagnoses for microcystin poisoning include leptospirosis, infectious canine hepatitis, aflatoxicosis, xylitol poisoning, toxoplasmosis, iron toxicosis, and hepatic neoplasia.

Differential diagnoses for anatoxin-a/anatoxin-a(s) poisoning include poisoning by organophosphate and/or carbamate insecticides, pyrethrins, and chlorinated hydrocarbons and should be considered in patients presented with acute CNS and peripheral nervous system signs, especially after being outdoors.

Diagnosis of cyanotoxin poisoning in a clinical setting should be based on clinical signs and exposure. Identification of algae in suspected ingested water or stomach contents/vomitus is suggestive of poisoning. Presence of toxins in the stomach contents is considered confirmatory. Tissue analysis can be difficult; however, some laboratories possess this capability, and clinicians are urged to contact their diagnostic laboratory for a referral. Many public health departments use an ELISA kit to detect microcystins in water samples. Recent literature suggests that the most practical sample to confirm microcystin exposure in a patient is antemortem testing of urine¹⁵; however, improvements are needed for this method to become practical for point-of-care use. Clinical pathologic findings associated with microcystin poisoning include but are not limited to thrombocytopenia, hypoglycemia, hyperbilirubinemia, increased ALT, and increased prothrombin and partial thromboplastin times.¹⁵ Confirmatory testing of tissue collected postmortem and histopathologic evaluation are often used for definitive diagnosis. Acute, severe, massive, hepatocellular necrosis is the main histopathologic finding associated with microcystin poisoning.¹⁵ 

Anatoxin-a poisoning is associated with rapid death, which limits pathologic assessment because often there are no lesions present or lesions are nonspecific.¹⁶ Stomach content or vomitus samples have the greatest diagnostic value and can be analyzed via liquid chromatography/tandem mass spectrometry to confirm exposure.¹⁶ However, this assay is not routinely offered. Anatoxin-a(s) does not cross the blood–brain barrier, so inhibition of blood acetylcholinesterase but not brain acetylcholinesterase may be supportive of anatoxin-a(s) exposure.¹⁷

Because there is no known antidote for cyanotoxin poisoning, treatment should be aimed at clinical signs. Cyanotoxins are rapidly absorbed from the GI tract, and decontamination is likely to have little benefit when the patient shows clinical signs. For patients with microcystin poisoning, IV fluid therapy, fresh frozen plasma, liver protectants, Vitamins E and K, gastroprotectants, antibiotics, and cholestyramine have all been used in combination with varying degrees of success. This is likely relative to the magnitude of exposure. Current therapy recommendations include cholestyramine,^18,19 IV fluids to replace volume and correct electrolyte abnormalities, glucose supplementation to address hypoglycemia, antiemetics to control vomiting, and antibiotics (if indicated by culture and susceptibility testing), to prevent secondary infections. Treatment should be aimed at combating hypovolemic shock and hemorrhage. Whole-blood transfusions may be necessary in severe cases.

Patients with anatoxin-a or anatoxin-a(s) exposure have such an acute and severe clinical presentation that treatment is often not possible prior to death. Respiratory support has been suggested but is not antidotal and likely only delays death. Anticonvulsants and methocarbamol have been used in cases of anatoxin-a poisoning, but treatment is often unsuccessful. Atropine may reduce clinical signs associated with anatoxin-a(s) poisoning, and although physostigmine and pralidoxime have been suggested for treatment, they do not appear to be of value after exposure.¹⁰ Because cyanotoxins have clinically steep dose-response curves, once clinical signs are observed it is likely that a sufficient amount of toxin has been absorbed to cause death.

Prognosis is grave for almost every patient, as morbidity and mortality are high for patients with confirmed exposure. There have been reports of successful intervention for microcystin poisoning in which exposure was relatively small and treatment was initiated quickly.²⁰ Even for patients with initial recovery from microcystin poisoning, prognosis should remain guarded due to complications relating to hepatic insufficiency. Follow-up examination in recovered patients should include monitoring liver enzymes and, potentially, coagulation parameters. Survival after anatoxin-a or anatoxin-a(s) exposure is rare and little is known about potential long-term complications.

Prevention of exposure is the most effective means of preventing clinical illness associated with harmful algal blooms. Cyanobacteria algal blooms are increasingly prevalent and likely to continue to cause illness.²¹ State agencies are aware of the risks these blooms pose and many have monitoring programs for recreational waters. There is ongoing research on preventive and mitigation techniques but there are no current effective economic solutions. More research is needed to accurately predict conditions contributing to algal bloom development.

The dose-dependent cardiovascular effects of α2 agonists have been well-characterized in numerous species and include increased systemic vascular resistance resulting in increased blood pressure, baroreceptor-mediated reflex bradycardia, decreased cardiac output, and a centrally mediated decrease in sympathetic tone.^1-3 Although not licensed for use in cats, atipamezole, an α2-adrenoceptor antagonist, is routinely used to reverse clinical effects of the α2 agonist dexmedetomidine. Previous research has shown that atipamezole effectively reduces dexmedetomidine-induced bradycardia in nonanesthetized cats.¹ 

This randomized crossover study investigated the effects of 2 clinically relevant doses of atipamezole versus saline solution administered to anesthetized cats that received dexmedetomidine. It was hypothesized that atipamezole would increase the pulse rate to values comparable with baseline and decrease mean arterial pressure as compared with 0.9% saline. Six healthy adult cats were anesthetized 3 times with a minimal 1-week washout period. Cats were induced with isoflurane, intubated, mechanically ventilated, and maintained with isoflurane. Standard anesthetic monitoring was performed in addition to continuous pulse rate and direct blood pressure monitoring. 

Following a 20-minute acclimation period, dexmedetomidine (5 μg/kg) was given IV over 5 minutes; cardiovascular variables (eg, pulse rate, mean arterial pressure, cardiac output) were measured before and 5 minutes after dexmedetomidine infusion. Either atipamezole at a low (25 μg/kg) or high dose (50 μg/kg) or saline solution was then administered IM. All variables were measured at defined intervals up to 120 minutes. 

Results revealed no benefit of IM atipamezole administration following dexmedetomidine in isoflurane-anesthetized cats. Although pulse rate increased significantly over time, there were no differences between groups. A significant decrease in mean arterial pressure with no increase in pulse rate as compared with saline was observed. In addition, treatment with atipamezole resulted in a transient (ie, lasting 15 minutes) but severe hypotension in some cats in both the high- and low-dose groups. The authors proposed that the failure to increase pulse rate and blood pressure was caused by a diminished baroreceptor reflex known to occur with inhalant anesthesia. It is likely atipamezole reversed the analgesia and anesthetic-sparing effects of dexmedetomidine.

Key pearls to put into practice:

Although atipamezole was ineffective at increasing pulse rate in isoflurane-anesthetized cats following dexmedetomidine administration, the results of this study should not be extrapolated to the reversal of dexmedetomidine in nonisoflurane-anesthetized cats.

Administration of atipamezole to isoflurane-anesthetized cats following dexmedetomidine administration shows no clear benefit and may be detrimental, causing transient but severe hypotension with no increase in heart rate.

Alternative anesthetic adjuncts should be considered to provide multimodal anesthesia in isoflurane-anesthetized cats, particularly in patients that may not tolerate the hemodynamic effects of α2 agonists or the consequences of reversal.

Traveling with a dog can be a significant source of distraction, and distracted driving is a major cause of vehicle accidents. In an accident, both dogs and humans are at risk from the unrestrained pet.

An online survey of dog owners in the United States, the United Kingdom, and Australia sought to determine the frequency with which restraints were used by pet owners traveling with their dog, as well as the factors involved in their decision to use or not use restraints. This study demonstrated that US owners were less likely to restrain their dog when traveling as compared with Australian or UK owners. Only ≈55% of the 706 surveyed US owners claimed that they always restrained their dog in the car; 67% of 637 Australian respondents and 72% of 692 UK respondents reported that they always restrained their dog while in the car.

Of note, only 6 US states have specific regulations limiting where or how dogs are allowed to ride in cars.¹ In the United Kingdom, however, the Highway Code has a specific statement describing suitable restraint for dogs in cars²; failure to comply with these regulations can lead to the driver’s car insurance being invalidated. Most of Australia’s regulations fall somewhere between these.³

Other findings regarding restraint of dogs by pet owners included:

• Small dogs were restrained more frequently than were larger dogs.
• Older owners were more likely to restrain their dog than were younger owners.
• Owners driving minivans or vans were more likely to restrain their dog than were those driving small- to medium-sized cars or SUVs.
• In the United States and United Kingdom, most dogs that were regularly restrained were restrained in crates or carriers. In Australia, a harness and tether attached to a seat buckle was most common.

Overall, the most common reasons reported for not providing restraint involved concerns for the pet’s comfort or that restraint was not believed to be necessary. Most owners noted a lack of guidance in choosing the appropriate car restraint for their dog and agreed that more information is needed. Most owners agreed that restraint devices for dogs should be safety tested.

Key pearls to put into practice:

Clinicians should be prepared to remind pet owners of the importance of safe pet restraint while traveling. Distance traveled should not be a factor in whether restraint is used.

Confinement in crates should be encouraged when possible, and clinicians can recommend resources to owners to help determine which restraint devices have been proven safe in testing (see Suggested Reading). Such resources could also be impactful for owners who believe restraint of their pet in the car is not critical.

Many owner misconceptions regarding the need for pet restraint can lead them to make inappropriate choices. Clinicians should help owners understand that all dogs, regardless of size, need to be safely restrained when traveling.

The prevalence of calcium oxalate (CaOx) urolithiasis is increasing, and CaOx is the most frequent urolith submitted for analysis in the United States.¹ Previous studies have identified breed predispositions for CaOx urolithiasis, but these were not conducted within the last decade and did not account for breed popularity in the United States.^1,2 

This study* sought to identify breeds at high and low risk for CaOx urolith development. Dogs that had CaOx uroliths analyzed at the University of Minnesota Veterinary Medical Center from 2010 to 2015 were compared with 3 control groups during the study period: 

• Dogs that formed nonCaOx uroliths 
• Dogs admitted without urinary tract disease
• A population from a breed popularity survey during a similar time period (2013-2016)

Breeds were considered to be at high or low risk if their odds ratio from all 3 control populations was >1 or <1, respectively, and statistically significant. Age and sex were also compared among the groups.

The following breed predispositions were identified:

Odds ratios also increased with male dogs, neutered dogs, and older dogs, although risk may decrease after 10 years of age. The mean age at discovery of the first CaOx urolith was 8.4 ± 2.8 years, with Brussels Griffons, Yorkshire terriers, and Pomeranians forming CaOx uroliths ≈1 year earlier. 

Key pearls to put into practice:

Risk for CaOx urolithiasis increases based on breed, increasing age, and neutered male signalment. 

Based on this study’s results, annual screening for CaOx uroliths in high-risk breeds should begin between 5 and 6 years of age or sooner if additional risk factors (eg, persistent CaOx urolithiasis, family CaOx urolith history, breed predisposition to CaOx urolith formation at an earlier age) exist. 

Annual screening for CaOx uroliths in high-risk breeds may help reduce the need for surgery, allow earlier interventions that prevent urolith recurrence, and allow earlier identification of predisposing comorbidities (eg, hypercalcemia, hyperadrenocorticism).

Six young cats from different households in the United Kingdom were diagnosed with Mycobacterium bovis infection, a member of the Mycobacterium tuberculosis complex. All were indoor-only cats and consumed the same commercial frozen raw feline diet. Seven subclinical in-contact cats from the affected households also had evidence of M bovis infection. Cats were presented with clinical signs including fever, inappetence, and severe weight loss and with diagnostic findings including pyogranulomatous lesions, abdominal mass, lymphadenopathy, and/or pneumonitis. Mortality rate was 83%. M bovis infection is zoonotic; commercial raw meat-based diets pose a significant risk for transmitting infectious pathogens such as M bovis to animals and their owners.

Chemoradiotherapy is considered the standard of care for certain cancers in humans and, although less common, has been used in veterinary patients. Chemoradiotherapy involves administration of chemotherapeutic agents prior to and during the course of radiation therapy as a radiation sensitizer to improve the response to local radiation, for the treatment of advanced locoregional disease, or for both local and systemic effects on tumors with a high metastatic potential.

Patients with incompletely excised high-grade or metastatic tumors require adjunctive therapy (ie, radiation and chemotherapy) to provide both adequate local and systemic control of their tumors. Although using these treatment modalities simultaneously can shorten overall treatment time, the risk for hematologic toxicity can be increased. This study aimed to determine whether dogs with microscopic mast cell tumors treated with radiation therapy and vinblastine/prednisolone demonstrated increased myelosuppression as compared with dogs treated with only vinblastine/prednisolone.   Forty-three dogs were treated with a combination of radiation therapy and vinblastine/prednisolone (RT/VBL/Pred); another 43 dogs were treated with vinblastine/prednisolone alone (VBL/Pred). Eight dogs (19%) in the RT/VBL/Pred group experienced neutropenia (6 VCOG [Veterinary Cooperative Oncology Group] grade I, 1 VCOG grade II, and 1 VCOG grade IV neutropenia) that resulted in a delay of chemotherapy, and 1 dog had a 10% dose reduction. Ten dogs (23%) in the VBL/Pred group experienced neutropenia (4 VCOG grade I, 2 VCOG grade II, and 4 VCOG grade III neutropenia), necessitating a dose delay in 10 dogs and a 10% dose reduction in 1. There was no significant difference in the frequency of neutropenia between the RT/VBL/Pred and VBL/Pred groups. The authors state that the study may have been underpowered to detect a difference. 

Although no increased risk for myelosuppression was shown when radiation therapy was administered simultaneously with vinblastine and prednisolone, this may not be the case when other chemotherapy agents are used. Other factors that can influence the risk for myelosuppression when combining radiation with chemotherapy include the radiation protocol (ie, number of fractions and total radiation dose) and the amount of bone marrow in the radiation field. In humans, a major factor associated with neutropenia or thrombocytopenia during radiation therapy is the percent of marrow being irradiated.  

Key pearls to put into practice:

Treating dogs concurrently with radiation and vinblastine can decrease overall treatment time without increasing the risk for myelosuppression, but different radiation protocols may not have the same result.

There may be an increased risk for myelosuppression associated with concurrent radiation therapy and chemotherapy when other chemotherapy agents are used and a greater amount of bone marrow is being irradiated.

Multimodal cancer therapy must be carefully planned and pet owners educated about the risk versus benefit for the patient.

Hookworms are the most significant soil-transmitted nematodes in humans, causing debilitating iron-deficiency anemia, which can become fatal in children, pregnant women, and the elderly. This study identified a naturally occurring, multidrug-resistant strain of the canine hookworm Ancylostoma caninum, which harbors a fixed, single-base pair mutation at amino acid 167 of the β-tubulin isotype 1 gene; the isolate was resistant to fenbendazole. The mutation was introduced into the corresponding amino acid in the nematode Caenorhabditis elegans and was found to confer similar resistance to thiabendazole and ivermectin. This study highlights the importance of understanding mechanisms of resistance for the design of parasite-control strategies.

One of the most common presentations in exotic animal medicine is rabbit GI stasis (RGIS), which may be primary or secondary. Despite its frequency, this syndrome is not well-identified, and etiologies range widely and can include toxicosis, infections, dental disease, neoplasia (GI or nonGI), diet, and environmental conditions. 

This study retrospectively examined commonalities in history, clinical, and laboratory findings in an effort to correlate them with etiologies and outcomes. Approximately 24% (n = 117) of the total rabbit caseload seen over a 2-year period was included in the study. 

Ultimately, 43 rabbits were diagnosed with RGIS without mechanical obstruction; only 1 was confirmed to have a physical obstruction (impaction of the distal descending colon). Radiographs identified medical issues that were not related to the GI tract in 23 (46%) patients.

Hematologic and serum chemistry values had no statistically relevant associations with short-term outcomes. However, 4 of 7 rabbits with moderate to severe serum creatinine levels, 2 of 3 rabbits with abnormal elevations of serum ALT activity, and 4 of 6 rabbits with marked serum lactate elevations died or were euthanized, suggesting a prognostic association with outcomes despite small sample sizes.

The most significant correlation to short-term outcomes was hypothermia. Thirty-four rabbits (29%) were hypothermic on presentation, with rectal temperatures <97.9o F (<36.6o C). These patients experienced an ≈4.6 times greater likelihood to die or be euthanized than were rabbits that were not hypothermic on presentation. 

Overall, outcomes and short-term prognoses for rabbits presented and treated for RGIS are good; in this study, 72% (84/117) of rabbits survived to hospital discharge, with 15 euthanized and 18 dying prior to discharge.

Key pearls to put into practice:

GI dysfunction is common in rabbits but has a good short-term outcome. 

Radiography is valuable but not necessary for determining GI obstruction. Mechanical obstruction causing RGIS appears to be uncommon, based on data from this study, and diagnosis is often challenging; for 18 of 50 rabbits for which abdominal radiography was performed, a boarded radiologist could not differentiate whether radiographic abnormalities noted were caused by functional ileus or mechanical obstruction.  

Clinical pathology findings have little correlation to outcome except in cases of significant abnormalities.

Hypothermia at presentation is a negative prognosticator.

Hyperthyroidism is a common endocrine disease in cats, with a reported prevalence of 8.4% to 11.7% in cats >10 years of age.¹ The disease is typically diagnosed based on elevated total thyroxine (T4) values and presence of typical clinical signs (ie, weight loss in conjunction with increased appetite, polyuria, polydipsia, vomiting, diarrhea, hyperactivity). A small percentage of cats with apathetic hyperthyroidism are presented with lethargy, obtundation, and poor appetite. 

Elevated total T4 values confirm a diagnosis of hyperthyroidism in 91% of cats²; however, the established population-based reference intervals for euthyroidism may not always be accurate, and some cats with normal values may be preclinically hyperthyroid. Many cats that have early stages of hyperthyroidism will fall in the high end of the normal reference range for T4. Free thyroxine (fT4) is the small percentage of T4 not bound to serum proteins. When elevated, fT4 has a sensitivity of 98% for diagnosis of hyperthyroidism and can be used as a second-line test in cats with high normal T4.² Still, there is a large day-to-day biologic variation in T4 and triiodothyronine (T3) values in hyperthyroid cats, and some patients with clinical disease fall within normal reference ranges; this variation is minimal in normal cats.³ 

This study evaluated biologic variation of T4, fT4, and thyroid-stimulating hormone (TSH) values in clinically healthy cats. For each of the 10 cats in the study, biologic variation, individual reference intervals, and index of individuality (ie, the ratio of the within-subject biologic variation to the between-subject variation) were determined for T4, fT4, and TSH values by measuring hormones weekly for 6 weeks. By comparing thyroid values over time and establishing each patient’s own reference interval, clinicians may detect thyroid dysfunction earlier. 

The reference change values for T4 and fT4 in this population of cats were ≈30%. Thus, a >30% increase in T4 or fT4 from the patient’s previous levels may suggest early hyperthyroidism. Relying only on population-based reference intervals might be misleading and could cause the clinician to miss changes in T4 values for individual patients that indicate preclinical hyperthyroidism, even though the values may fall within the normal population-based range.  

Key pearls to put into practice:

Obtaining T4, fT4, and TSH values during early mature life (ie, 5-8 years of age) might improve diagnosis of thyroid dysfunction by establishing an individual cat’s normal reference range.

A euthyroid cat with a previously detectable TSH value that becomes undetectable should be suspected of having emerging hyperthyroidism. 

Clinicians should not rely solely on laboratory-generated or population-generated reference intervals to diagnose thyroid disease; cats that have T4 values that are increased >30% but within normal population reference limits may still have preclinical hyperthyroidism.

Although they can be broken into immunologic and nonimmunologic responses, most adverse food reactions in dogs are suspected to be true immunologic food allergies involving immunoglobulin E (IgE)-mediated reactions. Cross-reactivity between seemingly unrelated food allergens has been shown to impact disease diagnosis and management in humans. 

This study* aimed to evaluate whether cross-reactive canine serum IgE-binding proteins could be identified in chicken and fish. Several methods (ELISA, inhibition ELISA, sodium dodecyl sulfate–polyacrylamide gel electrophoresis, immunoblotting inhibition) were used to assess the presence of cross-reactive proteins from chicken, white fish, and salmon in a large pool (n = 53 dogs) of canine serum. Results indicated the presence of at least 9 different cross-reactive canine serum IgE-binding allergens in whole extracts of chicken, white fish, and salmon; proteins identified included pyruvate kinase, creatine kinase, α actin, glyceraldehyde-3-phosphate dehydrogenase, enolase, aldolase, malate dehydrogenase, lactate dehydrogenase, and triosephosphate isomerase 1. Each of these proteins has been reported as a food component allergen in humans. This identification of IgE binding in canine serum supports the finding that shared allergenic proteins may be found in seemingly unrelated food sources. Clinical implications of this, however, have not yet been evaluated in dogs with documented food allergy.

Key pearls to put into practice:

Of note, the findings in this study were obtained from sera samples of dogs without a diagnosis of food allergy, highlighting that these serum-based allergen tests should not be used to determine whether a patient has allergies. These tests—both for food and environmental allergies (ie, atopic dermatitis)—may be “positive” in dogs that do not have any signs of allergy. They are not diagnostic; rather, they serve as a guide when formulating allergen-specific immunotherapy for patients with atopic dermatitis and to help confirm the clinical diagnosis.

The gold standard for diagnosing food allergy in dogs and cats remains a strict elimination diet trial. A recent literature review evaluated current information on in vitro and in vivo tests for food allergies in veterinary species. Results identified very low repeatability and low-/high-variable accuracy for various food allergy tests, confirming the importance of elimination diet trials in diagnosing food allergies.¹ 

Because these currently available tests use whole-allergen extracts with unknown concentrations of potentially relevant allergenic proteins, the clinical implication and accuracy of results may be impacted. Further evaluation of relevant IgE reactivity to more specific allergen components (eg, at the protein level) in food may eventually lead to more accurate diagnostic developments. At this time, an elimination diet trial is recommended.

• Most (65%) dogs achieved treatment success after the first CYTOPOINT injection.
• A second and third injection at monthly intervals increased treatment success to 85% and 93% of dogs, respectively.
• For dogs that did not achieve the desired response after the first injection, 79% were treatment successes with subsequent injections of CYTOPOINT.
• Four-week postinjection progress examinations were important to determine whether additional CYTOPOINT injections were of benefit.

Canine skin allergies—and accompanying pruritus—are the leading cause of yearly pet insurance claims.¹ However, treatment options for canine atopic dermatitis (AD) and associated pruritus are not always ideal. For example, the International Committee on Allergic Diseases of Animals considers antihistamines to be of little to no benefit in the treatment of acute flares of AD.^2,3 In addition, studies have suggested that 10% to 81% of patients receiving glucocorticoids or cyclosporine may experience adverse effects.⁴ Thus, clinicians may look for other treatment options for patients with a chronic disease that can impact patient’s and pet owner’s quality of life.⁵

CYTOPOINT (canine allergic dermatitis immunotherapeutic) is shown to be effective for the treatment of allergic dermatitis and atopic dermatitis in dogs.⁶

CYTOPOINT is a caninized monoclonal antibody that neutralizes interleukin31,⁶  a pruritus-inducing inflammatory cytokine.⁷ This therapy is safe and effective for dogs of all ages and sizes, those receiving a variety of concomitant medications, and those with comorbidiites.^8-12 CYTOPOINT is labeled for administration every 4-8 weeks as needed.¹³ A blinded, placebo-controlled pivotal field trial of CYTOPOINT in dogs with AD showed it was effective in reducing initial client pruritus visual analog scale (PVAS) scores by 50% or more in 57% of patients at 28 days.¹⁰ In addition, 69% of study dogs were regarded as treatment successes (defined as a minimum 20 mm reduction in PVAS) at day 28.¹⁰

In a retrospective study, ≈90% (87.8%) of patients with a variety of allergic dermatoses (eg, AD, adverse food reaction [AFR], allergic disease of undetermined cause [ADUC]) receiving CYTOPOINT were regarded as treatment success (defined as ≥20 mm on a PVAS).¹¹ Thus, CYTOPOINT has demonstrated efficacy not only in dogs with AD but also in dogs with other skin allergies, even when the specific cause of allergic dermatitis is uncertain.  

During CYTOPOINT’s conditional licensing period, Zoetis determined that some dogs responded incompletely to a single injection but demonstrated additional improvement after a second or third injection. A clinical study was conducted by Zoetis to assess the effect of additional CYTOPOINT injections in dogs with an initial incomplete response. The study investigators were veterinary dermatologists and the population included client-owned dogs that had confirmed AD and, at the time of entry into the study, had a PVAS score ≥50 mm and were free of ectoparasitic, bacterial, and fungal dermatitis. Candidates could also have diagnostically confirmed but actively managed flea allergic dermatitis in addition to AD.

Dogs in the study were prohibited from receiving potentially confounding medications (eg, glucocorticoids, antihistamines, cyclosporine, other antiinflammatory or immunosuppressant drugs). Limited exceptions were made for dogs receiving long-term therapy indicated to prevent allergic flares or for the treatment of unrelated conditions (eg, carprofen, omega-3 fatty acids, allergen-specific immunotherapy) if the patient had been stable on that medication for a number of months dictated by therapy category (eg, 3 months for incidental illness, 6 weeks for hypoallergenic diet, 8 months for desensitization immunotherapy).

Dogs that had a PVAS of ≥50 mm on the first day of the study (day 0) or ≥36 mm at any subsequent visit received a CYTOPOINT injection and were asked to return 30 days later (±3 days for owner convenience) for a total of up to 4 total visits (days 0, 30, 60, and 90). At each visit, a clinician performed a physical examination and collected the pet owner’s completed PVAS assessment. The PVAS assessment is a validated, easy, and repeatable method for owners to determine the severity of pruritus in their dog. A score is assigned on a sliding scale from 0 (normal dog) to 100 (extremely severe itch), with 20 mm representing very mild/occasional itching, 40 mm mild/frequent itching, and 60 mm moderate/regular episodes of itching.¹⁴

Of note, although patients with a 36-mm PVAS were given a CYTOPOINT injection and returned for a repeat visit, a 20-mm reduction in PVAS from the original starting point was considered a treatment success based on initial CYTOPOINT pivotal efficacy studies and subsequent assessment studies.^11,13  

On day 30, most (71/110 [65%]) dogs were treatment successes and completed the study (Table). The remaining 39 dogs were administered a second CYTOPOINT injection according to study protocol. At the day 60 visit, 23/39 (94/110 [85%] cumulative) were treatment successes and completed the study. The remaining 16 dogs were given a third CYTOPOINT injection. At 90 days, 8/16 (102/110 [93%] cumulative) were treatment successes.

If only the 39 dogs that did not respond completely to the first injection are considered, 23/39 (59%) and 31/39 (79%) achieved treatment success after a second and third injection, respectively.

Of 147 dogs originally enrolled in the study, 37 were removed from the final study evaluation. No dogs were removed due to the need for rescue with prohibited medications; 21 were removed due to missing data points, 3 due to the owner relocating, 2 due to adverse effects (2 patients had development of masses at sites other than the injection site; in both instances, a cause and effect relationship was not suspected), and 11 due to lack of owner compliance.¹³

Of note, for the 8 dogs that never responded completely to treatment, the mean PVAS score decreased only slightly after the first injection (Figure). This may suggest that dogs that initially show at least some improvement in the first 2 weeks—as compared with those that show no change at all—may be more likely to respond to therapy. 

This study was designed to determine a protocol to optimize treatment success for canine patients with AD. CYTOPOINT continues to appear highly effective in treating pruritus in dogs with AD. In initial pivotal studies, 69% of patients responded by day 28.¹⁰ Similarly, in the current study, 65% of patients had responded by day 30.

This study demonstrated that some dogs need additional time and CYTOPOINT injections to achieve optimal treatment success. Twenty-eight percent of total dogs in this study benefitted from a second and sometimes third injection.

The average half-life of CYTOPOINT is 16 days. Although the reason for the increased number of dogs achieving treatment success with a second and third monthly injection of CYTOPOINT is unknown, it may be due in part to increased CYTOPOINT exposure resulting from accumulation of the mAb over the first 2 to 3 doses based on pharmacokinetic modeling.

Dogs with even a partial response to an initial CYTOPOINT injection are likely to have additional beneficial responses to additional injections; this was true for 79% of dogs in this study. The small minority of dogs (8/110 [7%]) that do not benefit from additional injections are more likely to have had no response to the initial injection.

This study did not seek to examine whether treatment beyond a third injection at monthly intervals or whether greater intervals between injections had any impact on degree or duration of effect. These may be appropriate questions for further inquiry.

In a previous retrospective clinical study, 87.8% of dogs with AD, AFR, both AD and AFR, or ADUC responded to a single injection.¹¹ In the current study, the successful response rate to the first injection was only 65%. Differences in study results may be related to the retrospective nature of the previous study, differences in study populations, or in expected random variation. 

CYTOPOINT provides effective itch relief to most patients within 28 days. However, most dogs with only a partial response to the first injection may go on to achieve treatment success with a second or third injection. Dogs receiving CYTOPOINT should have a progress examination after 30 days and receive additional injections if necessary to optimize treatment success. 

A fundic examination is an important component of a thorough ophthalmologic examination and a complete physical examination. Fundoscopy may seem warranted only when a patient is presented with vision loss; however, the results of a fundic examination can be helpful when determining differential diagnoses and prognosticating. For example, patients presented for potential infectious, immune-mediated, vascular, neoplastic, nutritional, or metabolic disease may exhibit ocular manifestations of systemic disease. Proper examination of the fundus is not an inherently easy skill but, once mastered with practice and patience, is an invaluable tool.

The examination should be performed in a dimly lit, quiet room with an assistant stabilizing the patient’s head near the eye level of the examiner.^1,2 The patient should be in a seated position with minimal restraint. To achieve full view of the fundus, pharmacologic dilation of the pupil is necessary; otherwise, visualization of the peripheral fundus is impossible and lesions may be overlooked. The short-acting anticholinergic tropicamide (1%) is the preferred mydriatic agent for diagnostic purposes. One application typically results in mydriasis within 15 to 20 minutes that lasts 3 to 8 hours, depending on the degree of iris pigmentation.³ Examination of the anterior segment should precede administration of mydriatic drugs, which can confound the results of other diagnostic tests or exacerbate lens luxation and intraocular pressure elevation.^4-6

Two main techniques are used to evaluate the fundus: indirect and direct ophthalmoscopy. The most thorough examination is achieved via a survey view of the fundus with indirect ophthalmoscopy followed by examination of an identified lesion with the higher magnification used in direct ophthalmoscopy.

Indirect ophthalmoscopy can be performed via monocular or binocular examination, the latter of which requires a head-mounted light source and permits a greater degree of stereopsis (ie, depth perception). Both methods require a handheld condensing lens to form a magnified image of the patient’s eye. The following discussion describes use of monocular indirect ophthalmoscopy using a Finoff transilluminator as a bright light source. This method provides a more thorough examination of the fundus as compared with direct techniques and is more readily available than binocular examination. When performing indirect ophthalmoscopy, the examiner’s head, the light source, and the condensing lens should act as a unit, pivoting together on an axis (Figures 1 and 2); alignment is of utmost importance. Indirect ophthalmoscopy produces a reversed and inverted (ie, upside down and backward) image and allows a larger, panoramic field of view as compared with direct techniques (Figure 3).² Magnification is inversely proportional to the diopter strength (ie, focal length) of the convex lens used. A lower diopter strength results in greater magnification with a smaller field of view, whereas a higher diopter strength results in lower magnification but a larger field of view.² Lenses between 20 diopter (D) and 30D are most commonly used for examining dogs and cats, although lenses can have a wider range (up to 40D). Additional advantages of indirect ophthalmoscopy include a safer working distance from the patient and increased ability to view the fundus through opacities in ocular media.

Most dogs and cats have a tapetum lucidum, the brightly colored reflective structure located in the choroid that gives the fundus its “eyeshine.” Patients that do not possess a tapetum—usually those with lightly colored or blue eyes—have a red fundic reflection that originates from illumination of the choroidal vasculature. This should not be confused with posterior segment hemorrhage.

Direct ophthalmoscopy provides a direct, upright image of the patient’s fundus. The image seen by the examiner is noninverted and magnified 15 to 17 times.¹ However, the field of view is much more restricted as compared with indirect techniques due to the higher magnification. Direct ophthalmoscopy enables description and characterization of focal fundic lesions and close examination of the optic disc. Patience is required to complete a thorough examination because a much larger series of vignettes must be acquired to piece together the entire fundus. In addition, visualization of peripheral fundic lesions with direct ophthalmoscopy is practically impossible, particularly if the eyes are not dilated. 

A direct ophthalmoscope has many adjustable settings. The rheostat allows the light intensity to be controlled and should be kept low to ensure patient comfort and an accurate view for the examiner. If the pupil cannot be dilated, the patient should be examined in a darkened room and the rheostat adjusted to minimize pupillary constriction. An aperture dial and filter switch on the patient side of the ophthalmoscope allow adjustment of the size, shape, and color of the light beam. The smaller apertures should be used for nondilated eyes and the larger apertures for dilated eyes. The specific filters and apertures vary by instrument, but most include a slit beam for evaluating fundic elevations and depressions, graticule grid for size estimation, cobalt blue light for corneal fluorescein dye excitation, and red-free light for differentiation of hemorrhage (appears black) and pigment (appears brown). A series of concave and convex lenses located on the rotating diopter dial allow both depth adjustment and focus to bring structures at different levels into view (Figure 4). A direct ophthalmoscope may also be used to evaluate the anterior segment of the eye with magnification. The dial must be changed to the positive diopter settings to view the anterior segments (Figure 5). If the examiner’s vision is not emmetropic (ie, ideal vision without focusing deviations or visual defects), the initial dial setting at which the normal fundus is in focus will not be 0. Each subsequent setting must be interpreted in the light of the initial setting.

Advantages of direct ophthalmoscopy include close evaluation of fundic lesions, accessory features, and lower equipment cost as compared with indirect ophthalmoscopy. Disadvantages include the lack of stereopsis, small field of view, proximity of the examiner’s face to the patient, limited evaluation of the peripheral fundus, and impaired visualization of the fundus through opaque anterior ocular structures (eg, corneal edema, nuclear sclerosis).

• Dilating agent (eg, 1% tropicamide ophthalmic solution)
• Focal light source (eg, Finoff transilluminator, high-quality pen light)
• Indirect condensing lens (between +40D and +20D)
• Direct ophthalmoscope

While sitting or standing an arm’s length away from the patient and holding the light source next to the dominant eye so that the examiner’s head and light source move as a single unit, use the opposite hand to hold and position the lens. Hold the lens between the forefinger and thumb with the flatter surface toward the patient and more convex surface toward the examiner. Position the light beam—keeping light intensity low to avoid obscuring details or disturbing the patient—until a bright reflection from the patient’s fundus is observed.

Locate the tapetal reflection, then place the lens 2 to 4 cm from the corneal surface and perpendicular to (ie, in the path of) the light beam while keeping the remaining fingers in contact with the patient’s head.

Hold the condensing lens parallel to the iris with the lens axis in alignment with the pupil axis to maintain a stable fundic image. Ensure the examiner’s head, light source, and condensing lens act as a unit, pivoting together on an axis. If the view of the fundus is lost, remove the indirect lens, re-establish visualization of the tapetal reflection, and replace the lens in front of the eye.

Move around, being sure to maintain a constant tapetal reflection, to observe the entire fundus, especially the periphery, and to follow the patient’s eye.

Turn on the ophthalmoscope and set the light to the correct aperture based on whether the eyes are dilated. Rest the brow on the brow rest.

While holding the ophthalmoscope in the dominant hand and using the opposite hand to stabilize the patient’s head and keep the eyelids open, use the right eye to look through the instrument and examine the patient’s right eye. Repeat using the left eye to examine to the patient’s left eye.

Locate the patient’s fundic/tapetal reflection from approximately an arm’s length distance, then move 2 to 4 cm from the patient’s eye to widen the field of view. Adjust the lens settings so the fundus is in focus.

Identify the optic nerve, then thoroughly examine the remainder of the fundus in quadrants.

Hypertension affects ≈20% of cats¹ and is often linked to other common feline diseases—most frequently chronic kidney disease^1,2 but also hyperthyroidism. Untreated, chronic, progressive hypertension has the potential to cause significant morbidity, including target organ damage (eg, eyes, brain, heart, kidneys).^3-5

Diagnosing hypertension early is beneficial for preventing target organ damage. In one study, cats diagnosed with systemic hypertension as part of a screening protocol had improved survival as compared with those that were diagnosed after being presented with clinical signs.¹ A hypertension diagnosis may prompt further screening due to the disease’s correlation with other conditions. Hypertension and renal disease are often intertwined, with up to 74% of hypertensive cats also being azotemic and up to 65% of cats with CKD found to be hypertensive.^4-9

The AAFP, AAHA, ACVIM, and International Society of Feline Medicine (ISFM) all recommend yearly screening in older cats, though recommended starting ages vary between 7 and 11 years.^2-4,10

Before senior screening can be pursued, pet owners must bring their cat to the clinic. However, 21% of cat owners report taking their senior cat to the vet less than they did when it was young.¹¹ Further, some of the most recent data suggest that only ≈35% of senior cats presented to a clinic receive senior screening.¹² Anecdotally, the percentage of clinics performing the type of screening relevant to hypertension (eg, sphygmomanometry, routine retinoscopic examination, urinalysis) is likely even lower, although published data are not readily available. It is up to the veterinary team to help get more senior cats to the clinic and recommend appropriate hypertension screening.

Many owners may assume their cat is self-sufficient and in excellent health, especially if it has never been sick or lives completely indoors. In addition, cats typically hide signs of illness from their owner. Owners may perceive their cat as stressed at a veterinary appointment,¹¹ which can create challenges in handling and testing accuracy. In addition, some veterinary teams may have limited availability to appropriate clinic space for stress-free screening, adequate screening tools, time to thoroughly train staff, and/or time to perform accurate assessments.

Awareness of the need for low-stress environments and handling for cats has increased.¹³ There is an increasing number cat-oriented organizations that offer programs and resources designed to increase pet owner awareness, facilitate comfortable feline visits, and reduce avoidance of future appointments.

Because up to 100% of hypertensive cats may have retinal lesions,¹⁰ and because it is a noninvasive element of the physical examination, fundoscopy can be a powerful hypertension screening tool. In the same way practitioners perfect auscultation or palpation skills, routine ocular screening can improve clinicians’ confidence and accuracy over time. A guide to performing a reliable fundic examination is provided in the April 2020 issue of Clinician’s Brief and on clinciansbrief.com. Abnormal findings can encourage reluctant pet owners to agree to additional screening.

There are many potential benefits to making hypertension screening routine so that every senior patient receives a blood pressure (BP) measurement. Routine testing may help staff members and clinicians obtain a patient’s baseline values and understand what to expect for patients with different temperaments. It may also acclimate patients to the procedure. Routine BP measurements are opportunities to empower staff members, especially veterinary nurses, and to conserve clinicians’ limited time.

Doppler sphygmomanometry and/or high-definition oscillometry are commonly used for measuring BP in cats.⁴ Regardless of the device used, a consistent protocol for BP measurement is essential for obtaining reliable values.¹⁰ Detailed guidelines are available from ACVIM and ISFM (see References).^4,10 Teams can adapt their approach to minimize stress to their unique patient and practice environment; for example:

The patient exits the carrier on its own and is given 5 to 10 minutes to explore a quiet room. Before the physical examination, a staff member provides the patient with a warmed blanket for comfort and measures the patient’s BP.^4,10 One staff member is trained in the protocol and responsible for all measurements.¹⁰ Either the tail or a limb is used, and the cat is kept still.¹⁰ The average of multiple measurements is determined after discarding the first measurement.¹⁰

Key obstacles to routine urinalysis include lack of understanding by owners about its importance and their concerns about cost and urine collection. Proteinuria is significantly correlated with all-cause mortality, including mortality related to hypertension and chronic kidney disease.¹⁰ The ACVIM recommends routine urinalysis, including dipstick protein measurements, for all senior cats as part of the annual minimum database.³ The results of this simple test can support the need for futher hypertension and/or renal screening.

Increasing wellness visits for senior cats and implementing an appropriate routine minimum database, including routine fundic examination, BP screening, and urinalysis, is essential for early disease detection, prevention, and management^2-4,10 and provides a great opportunity for educating owners. Early identification and timely treatment of hypertension and/or associated conditions may increase both survival time and quality of life in senior cats.¹