Materials and Methods

Criteria for case selection—The computer database of the American Society for the Prevention of Cruelty to Animals' APCC was searched for records related to dogs that ingested MPH from November 1, 2001, to November 30, 2008. The database contains records of calls (recorded by APCC staff) from animal owners and veterinarians in the United States and Canada regarding suspected cases of poisoning in animals. A dog was included in the study if the case was classified as MPH toxicosis, suspected toxicosis, or exposure; these classifications were assigned by the APCC staff member (a veterinarian or veterinary toxicologist) that managed each case and were determined on the basis of history, clinical information, expected clinical signs (ie, signs of CNS and cardiovascular stimulation), and the evaluator's previous experience. Dogs that ingested other compounds in addition to MPH were excluded from the study, and because the intent of the study was to evaluate reports of dogs that ingested MPH pills, dogs that met all other criteria but were reported to have ingested MPH transdermal delivery patches were also excluded.

Estimation of drug dose and classification of cases—The APCC staff member that managed each case estimated the dose of MPH on the basis of information obtained from the caller (usually the owner or the veterinarian that treated the dog). Certainty regarding the dose of MPH that was ingested was assigned to 1 of 6 categories (observed, evident, suspected, possible, nonspecific, or unknown), and cases were assigned 1 of 5 classifications (toxicosis, suspected toxicosis, possible toxicosis, doubtful toxicosis, or exposure only) according to internal APCC protocols.

The dose was assessed as observed when the animal was seen ingesting the reported amount, as evident when adequate objective information to confirm the amount (eg, a specific amount of medication missing) was provided, as suspected when the caller expressed confidence that a certain amount was ingested but did not provide substantial evidence to exclude another amount, as possible when an amount was reported that might have been ingested but no direct evidence was received to confirm the amount, as nonspecific when the caller expressed certainty that an ingestion had occurred but the amount could not be estimated, and as unknown when the owner was not sure whether exposure had occurred.

On the basis of the information obtained from the initial call, subsequent calls to assist with acute toxicosis, and follow-up calls to attempt to obtain outcome data, an APCC veterinarian or veterinary toxicologist assigned an assessment classification to each case. A case was classified as toxicosis if all historical, clinical, and temporal data were consistent with the expected clinical syndrome; as suspected toxicosis if all available data were consistent but some data were missing; as possible toxicosis if some but not all available data were consistent with the expected clinical syndrome; and as doubtful toxicosis if the data were not consistent with the expected clinical syndrome. Cases involving ingestion of MPH without subsequent development of clinical signs were classified as exposure only

Records review—Information collected from the records included breed, sex, age, weight, source and history of exposure, estimated dose, clinical syndrome (eg, signs, onset, and duration), outcome, and number of animals affected.

Statistical analysis—Spearman rank sum correlation coefficients were calculated for MPH dose and the number of clinical signs, MPH dose and heart rate in tachycardic (heart rate ≥ 140 beats/min) dogs, and MPH dose and temperature in hyperthermic (rectal temperature ≥ 39.7°C [103.4°F]) dogs because the data were not distributed normally. Associations between dose and whether a dog had clinical signs of toxicosis (yes = 1; no = 0) were compared via a Wilcoxon rank sum test. Values of P ≤ 0.05 were considered significant.

Results

The records search revealed 1,205 dogs with potential MPH ingestion. Of 1,205 dogs, the records of 1,077 were excluded from analysis on the basis of case classification (ie, assessed as possible toxicosis or doubtful toxicosis), exposure to other compounds in addition to MPH, or ingestion of MPH transdermal delivery patches. For cases included in the study, dogs were observed to ingest MPH pills, or other direct evidence of ingestion was reported (such as a prescription bottle on the floor with missing pills). Records were retrieved for 124 calls regarding ingestion of MPH pills by dogs; because 4 calls involved 2 dogs each, 128 dogs were enrolled in the study. Although MPH is occasionally used in veterinary medicine to treat narcolepsy and hyperactivity,^9,11,12 the MPH ingested by dogs in the study reported here was intended for use in humans.

Twenty-seven of 128 (21%) dogs in the study were mixed-breed dogs, 15 (12%) were Labrador Retrievers, 8 (6%) were Cocker Spaniels, and 6 (5%) were Shih Tzus; no other breed comprised > 4% of case dogs. Forty-five of 128 (35%) dogs were < 1 year old, 74 (58%) were 1 to 10 years old, and 9 (7%) were ≥ 10 years old. The reports originated from 32 states in the United States and 1 Canadian province.

Certainty regarding the dose of MPH was classified as observed for 44 dogs, evident for 47, suspected for 8, possible for 21, unknown for 7, and nonspecific for 1. The range of doses ingested was 0.36 to 117.0 mg/kg (0.164 to 53.2 mg/lb); mean and median doses were 12.6 mg/kg (5.73 mg/lb) and 5.7 mg/kg (2.59 mg/lb), respectively. The lowest dose ingested by a dog that had clinical signs of toxicosis was 0.39 mg/kg (0.177 mg/lb); the highest dose for which no clinical signs were reported was 30.0 mg/kg (13.64 mg/lb). Clinical signs were reported for 107 of 128 (84%) dogs; of the 21 remaining dogs, lack of any clinical signs associated with the ingestion was confirmed for 16, but 5 dogs were lost to follow-up. It is possible that these 5 dogs may have developed clinical signs subsequent to the call placed to the APCC. Among dogs that had clinical signs, the mean and median doses of MPH were 14.1 mg/kg (6.41 mg/lb) and 5.9 mg/kg (2.68 mg/lb), respectively (range, 0.39 to 117.0 mg/kg).

The most frequently reported clinical signs following MPH ingestion were behavioral or neurologic. Because neurologic and behavioral signs are classified separately in the APCC database, they were analyzed and reported as such in the study reported here, although behavioral signs may also be considered a subset of nervous system signs. Agitation, hyperactivity, pacing, clinging, and inappropriate urination were classified as behavioral signs, and circling, excitation, tremors, lethargy, anxiety, fasciculations, depression, disorientation, head bobbing, restlessness, ataxia, and somnolence were classified as neurologic signs. Cardiopulmonary and digestive systems were also frequently affected. The most commonly reported clinical sign of toxicosis after MPH ingestion was hyperactivity, which was recorded for 42 of 128 (33%) dogs. Other clinical signs reported included tachycardia (range, 140 to 250 beats/min) in 27 (21%), vomiting in 19 (15%), agitation in 16 (13%), hyperthermia (range, 39.7° to 42.6°C [103.4° to 108.6°F]) in 13 (10%), panting in 11 (9%), and mydriasis in 8 (6%) dogs. Anxiety, tremors, and vocalization were each reported in 6 (5%) dogs; circling and restlessness were each reported in 5 (4%) dogs. Of 14 dogs that ingested doses < 1.0 mg/kg (0.45 mg/lb), 11 had clinical signs; these were multiple in 3 dogs, including 1 that had 6 clinical signs (Table 1).

Outcome data were available for 34 of 128 (27%) dogs. Of these 34 dogs, 16 (47%) did not develop clinical signs of toxicosis, 15 (44%) had clinical signs but were reported to have full recoveries, and 3 (9%) died or were euthanatized. The dose ranges for dogs in these groups were 0.36 to 30.0 mg/kg, 1.32 to 30.0 mg/kg (0.60 to 13.63 mg/lb), and 10.2 to 31.1 mg/kg (4.64 to 14.14 mg/lb), respectively. Early emesis (ie, within 1 hour of ingestion for 9 dogs and between 1 and 2 hours after ingestion for 1 dog) was induced in 10 of the 16 dogs that did not develop clinical signs.

Dogs included in the study were categorized into 2 groups: those that ingested IR formulations (n = 28) and those that ingested any type of ER MPH formulation (100). Twenty-five of 28 (89%) dogs that consumed IR MPH pills had clinical signs of toxicosis. The mean and median doses of MPH in dogs that ingested IR pills were 5.05 mg/kg (2.295 mg/lb) and 3.72 mg/kg (1.690 mg/lb), respectively (range, 0.36 to 36.8 mg/kg [0.164 to 16.73 mg/lb]), and the minimum toxic dose was 0.59 mg/kg (0.268 mg/lb). Outcome data were available for 5 (18%) dogs in this group; 2 of these developed no clinical signs, and 3 had clinical signs but had full recoveries.

Eighty-two of 100 (82%) dogs that ingested ER MPH pills had clinical signs of toxicosis. The mean and median doses of MPH in dogs that ingested ER pills were 14.3 mg/kg (6.50 mg/lb) and 6.55 mg/kg (2.977 mg/lb), respectively (range, 0.39 to 117.0 mg/kg), and the minimum toxic dose was 0.39 mg/kg. Final outcome data were available for 29 (29%) dogs; 14 developed no clinical signs, 12 had clinical signs but had full recoveries, and 3 died or were euthanatized.

The types of clinical signs were similar among dogs in the IR and ER groups, and the mean number of clinical signs reported (2) for dogs in the 2 groups was identical. Among dogs that consumed IR pills, onset of signs ranged from within a few minutes of ingestion to 9.5 hours afterward, with the exception of 1 dog that developed signs > 24 hours after ingestion. However, the opinion of the APCC veterinarian that received the call was that MPH did not cause these signs (the same dog had other signs that developed much closer to the time of ingestion that were attributed to MPH). Most clinical signs developed within 3 hours of ingestion in dogs in this group, and with the exception of 1 dog previously mentioned, signs were reported to persist > 12 hours after ingestion of MPH in only 1 dog that ingested an IR formulation. Onset of clinical signs among dogs that consumed ER MPH formulations ranged from within minutes to slightly more than 24 hours after ingestion. While most signs resolved within 12 hours, 11 (11%) dogs that ingested ER MPH pills had clinical signs that persisted > 12 hours after ingestion.

The 3 dogs in the present study that died following MPH ingestion had consumed ER formulations of the drug; doses that resulted in death were 10.2, 15.4, and 31.1 mg/kg (4.64, 7.00, and 14.14 mg/lb). One of these 3 dogs was euthanatized following a dose of 15.4 mg of MPH/kg, 1 died of cardiac arrest (dose, 31.1 mg/kg), and the exact manner of death in 1 dog (dose, 10.2 mg/kg) was not specified.

The Spearman rank sum correlation coefficient for dose and number of clinical signs was 0.17 (P = 0.63 [n = 120 dogs for which dose could be calculated]), that for dose and heart rate was 0.13 (P = 0.53 [24]), and that for dose and temperature was 0.73 (P = 0.048 [8]). No significant (P = 0.28) association was detected between dose and whether or not clinical signs were present (n = 120).

Clinicopathologic data were not available except for a few cases, and analysis of these results did not reveal any significant abnormalities.

Discussion

Methylphenidate is a CNS stimulant similar to amphetamines, but it has more mental effects and fewer motor effects than do amphetamines.^3,13 Oral administration results in rapid and nearly complete absorption in humans, and evidence suggests the same is true in dogs.^1,5 Because the drug is highly soluble in lipids and is not highly bound to proteins, it rapidly enters the CNS where it is thought to affect concentrations of dopamine and possibly norepinephrine and serotonin.^4–7 Following oral administration, most (up to 86%) MPH is eliminated by urinary excretion¹⁴; the drug is transformed into 2 major metabolites that account for 90% of the urinary excretion product in humans but only 50% of that in dogs.¹⁴

Most dogs in the present study showed clinical signs resulting from sympathomimetic effects similar to those reported in MPH toxicosis in humans.^5,6 Abnormal behavior, commonly reported as hyperactivity, agitation, or pacing, was also observed in most dogs in the present study. It is likely that these behavioral changes were the result of changes in neurotransmitter concentrations. Similar behavioral changes were reported in Beagles that received daily doses of up to 20 mg/kg of MPH for 90 days during laboratory experiments.^1,10 Vomiting was reported in 19 of 128 (15%) of the dogs in this study; to the authors' knowledge, this had not been reported in other studies involving dogs but it had been reported in humans.⁶

In dogs of the present study, the minimum toxic doses of MPH were 0.59 and 0.39 mg/kg of the IR and ER formulations, respectively. Pemoline, another amphetamine-like drug that has been used to treat ADHD in humans, has been shown to cause clinical signs in dogs at doses of > 2.8 mg/kg (1.27 mg/lb).¹⁵ The types of clinical signs detected in dogs with MPH toxicosis were similar to those reported in dogs that ingested pemoline,¹⁵ although no vomiting was reported in the latter dogs. The severity of tachycardia and hyperthermia was greater in dogs that had MPH toxicosis, compared with dogs that had pemoline toxicosis, and was similar to clinical signs reported^16,17 in dogs that ingested amphetamines and amphetamine-like drugs.

Methylphenidate is available in various IR and ER formulations for oral administration. In the study reported here, all oral formulations that delayed the release of any portion of the MPH contained in the pill were categorized as ER formulations. The development of ER products served to reduce the abuse potential and alleviate the necessity for multiple doses that exists with the short half-life of the IR formulations.² There are 3 basic types of ER MPH pills. The first ER pill to be developed had a wax matrix and was less clinically efficacious in humans than was the IR formulation.^1,18 Peak plasma concentrations of MPH were detected 4.7 hours after oral administration of wax matrix pills in humans.⁶ Subsequently, pills were developed that deliver the drug via an osmotic pressure system, and other pills were developed that contained microbeads for this purpose. Peak plasma concentrations for the osmotic pressure-release system pills were detected between 6.7 and 7.7 hours after oral administration in humans.⁶ Microbead pills contain a fixed percentage (30% or 50%) of IR beads, and the remainder comprises ER beads; therefore, they have biphasic peak plasma concentrations.^2,6 The initial peak occurs between 1.5 and 2 hours and the second peak occurs between 4.5 and 6.6 hours after oral administration in humans.⁶ Clinical effects of the ER formulations are intended to persist for 8 to 12 hours in humans.^2,6,7 Peak plasma concentrations of MPH following administration of IR pills have been reported to occur within 1 to 2 hours of ingestion in dogs and within 1 to 3 hours in humans, and the duration of action is reportedly 1 to 4 hours in humans.^1,2,4,6 Of 100 dogs that consumed ER pills in our study, 61 (61%) ingested pills that had an osmotic pressure drug delivery system, 31 (31%) ingested microbead formulations, and 8 (8%) ingested wax matrix pills.

Clinical signs in dogs that ingested ER MPH pills persisted longer than those associated with IR MPH consumption; however, interpretation of data regarding onset and duration of clinical signs in the present study is complicated by multiple factors. Not all dogs in the study received the same management (eg, different time intervals between ingestion and treatment and different types of treatment), and the manner in which the drug was consumed may have been different between different dogs. Some dogs may have swallowed the pills whole, and others may have chewed the pills. Chewing an ER pill could alter the kinetics by making more or possibly the entire amount of MPH in the pill available for immediate absorption. Additionally, the mean dose was much higher for the ER formulations; these typically contain more milligrams of drug per pill because they are intended to last for a longer period of time.

The results of statistical analyses did not reveal a significant relationship between dose and presence of clinical signs, dose and number of clinical signs, or dose and heart rate in tachycardic dogs. Although the relationship between dose and hyperthermia was significant, only a small number of dogs (n = 8 dogs for which the relevant information was available in the APCC database) was used to determine this relationship. Because this was not a controlled study, temperature and heart rate measurements were not all recorded at the same time point relative to MPH ingestion. In the study reported here, dogs that consumed the lowest doses of MPH (whether of ER or IR pills) had a likelihood of developing clinical signs that was similar to that of the entire population (ie, 107/128 dogs developed clinical signs; 11/14 dogs that consumed < 1.0 mg/kg of MPH developed clinical signs). In humans, clinical effects and pharmacokinetic parameters of MPH vary greatly and many of the adverse effects are not dose related.^6,7 Results of the present study suggest a similar pattern may exist in dogs.

An MPH dosage of 0.25 to 0.50 mg/kg (0.114 to 0.227 mg/lb), PO, every 12 to 24 hours is recommended for the treatment of narcolepsy in dogs.⁹ For treatment of hyperactivity, a dose of 5 mg/dog, PO, every 12 hours is suggested for small dogs and up to 40 mg/dog, PO, every 12 hours may be administered in large dogs.⁹ Higher doses than these were consumed by most of the dogs in the present study, but signs of toxicosis occurred following ingestion of doses as low as those recommended for treatment of narcolepsy and for hyperactivity. Severe clinical signs, similar to those reported in the present study, were reported in a cat that ingested a dose of 0.98 mg/kg (0.445 mg/lb); those signs resolved within 25 hours.¹¹

Dogs in the present study that died or were euthanatized had all ingested ER MPH pills. The significance of this is not clear because most (100/128 [78%]) of the dogs consumed ER pills and there were only 3 deaths out of 128 (2%) cases of MPH ingestion. The doses that were associated with death (10.2, 15.4, and 31.1 mg/kg) in the study reported here were substantially higher than the lowest reported⁹ lethal dose (3.1 mg/kg). Ninety of the 125 surviving dogs of the present study had consumed higher doses than did the nonsurviving dogs, and early emesis had been induced in the majority (10/16 [63%]) of dogs that never developed clinical signs. It is possible that much of the ingested drug was eliminated in this manner before it was absorbed. Treatment given to dogs that subsequently had full recoveries consisted primarily of decontamination (via early emesis and administration of activated charcoal).

In the study reported here, the diagnosis of MPH toxicosis in all cases was made on the basis of history and reported clinical syndrome, and no confirmatory tests were performed. Confirming a diagnosis of MPH toxicosis in a dog can be challenging because there are no specific tests to detect MPH in this species. Tests that detect metabolites of MPH in human urine are available and could potentially be used to confirm exposure in dogs. In addition, tests designed to detect amphetamines in human urine could potentially prove useful to confirm a diagnosis of MPH toxicosis in dogs because of the similarity of metabolites between amphetamines and MPH.

Currently, management of MPH toxicosis is similar to management of other sympathomimetics, such as amphetamines, and primarily relies on supportive care. The goals of treatment are decontamination, control of cardiovascular and CNS abnormalities, reduction in body temperature of hyperthermic dogs, and correction of acid-base and electrolyte disturbances. Intensive monitoring is required because MPH can potentially affect many different body systems.

Decontamination should include induction of emesis with 3% hydrogen peroxide (1 to 2 mL/kg [0.45 to 0.91 mL/lb], PO) or apomorphine (0.03 to 0.04 mg/kg [0.014 to 0.018 mg/lb], IV or 0.04 to 0.08 mg/kg [0.018 to 0.036 mg/lb], IM)¹⁹ if no clinical signs are present and < 2 hours have passed since ingestion of ER pills; IR pills dissolve quickly and are unlikely to be recovered if > 1 hour has elapsed since ingestion. Potential adverse effects of hydrogen peroxide administration include severe vomiting and mucosal irritation or ulceration.²⁰ Adverse effects of apomorphine include protracted vomiting, depression, and excitement.⁹ Signs of CNS disturbance, which were reported frequently in the study reported here, are contraindications for the induction of emesis.²⁰ It should be emphasized that induction of emesis is only recommended in dogs that do not have clinical signs of toxicosis. There is likely no benefit to emesis > 1 hour after ingestion of the IR formulation or > 2 hours after ingestion of the ER formulation of MPH.¹⁹

If emesis is ineffective or contraindicated, the use of activated charcoal can be considered with or without a cathartic.⁶ Activated charcoal and cathartics are commonly used to treat intoxications, but there are currently no data available that support or refute their effectiveness in treatment of MPH toxicosis in dogs. The use of activated charcoal with or without a cathartic is no longer routinely recommended as treatment for intoxication in humans because there is no evidence that it contributes to improved patient outcomes.^21,22 Additionally, significant risks are associated with the use of activated charcoal and cathartics, including aspiration pneumonia, dehydration, and electrolyte abnormalities.²⁰ Decisions regarding the use of activated charcoal, cathartics, or both should be made after careful consideration of potential risks and benefits. If it is determined that activated charcoal is indicated, it can be administered (1.0 to 4.0 g/kg [0.45 to 1.82 g/lb], PO) mixed with 50 to 200 mL of water, with or without a cathartic.¹⁹ Magnesium sulfate (250 mg/kg [113.6 mg/lb]) and sodium sulfate (250 mg/kg) are frequently administered cathartics; a 70% sorbitol solution (1 to 2 mL/kg, PO) can alternatively be given.¹⁹ Activated charcoal should be given as soon after the ingestion of MPH as possible and may be ineffective if given > 2 hours after ingestion of IR formulations.

If emesis is contraindicated, gastric lavage can be performed after the patient is anesthetized and a cuffed endotracheal tube is in place; activated charcoal and a cathartic can be administered via a stomach tube following lavage.¹⁹ However, gastric lavage is also no longer recommended for use in humans that have ingested toxic substances because of potential risks and the lack of evidence that the procedure improves outcome.²³ A less invasive alternative to gastric lavage is nasogastric intubation and aspiration, but clinical evidence regarding its efficacy in canine patients is lacking. Regardless of the method used, the effectiveness of decontamination is directly related to how soon it is administered after ingestion of the toxic substance. Urinary acidification, which historically has been used to increase elimination of amphetamines in humans, is no longer recommended due to the potential for renal injury.²⁴

Acepromazine may block dopamine receptors and inhibit the release of dopamine; it should be administered (0.025 to 0.2 mg/kg [0.011 to 0.09 mg/lb], q 4 to 6 h, IV, IM, or SC) to control hyperactivity, agitation, tremors, pacing, excitement, and other behavioral changes.⁹ Chlorpromazine (3 mg/kg [1.4 mg/lb], IV; titrated up as needed to effect) may be given in place of acepromazine.⁹ Stimulation of the CNS should be reduced by placing the dog in a quiet and dark environment with minimal handling. Diazepam, although recommended to control seizures in human amphetamine toxicosis, is not recommended for use in dogs in this situation because it has been associated with increased excitement in dogs with amphetamine toxicosis.¹³ Seizures may initially be controlled with propofol (0.1 to 0.6 mg/kg/min [0.05 to 0.27 mg/lb/min, IV]) given along with a longer acting agent such as phenobarbital (2.0 to 5.0 mg/kg [0.91 to 2.27 mg/lb], IV, q 20 min up to 2 times).⁹ The use of propofol requires establishment of an airway and constant patient monitoring. Propranolol is a nonspecific β-adrenoceptor blocker that may be administered (0.02 to 1.0 mg/kg [0.009 to 0.45 mg/lb], IV or 0.1 to 0.2 mg/kg, PO, q 8 h) to control tachycardia and as an antiarrhythmic.⁹ Methocarbamol, a muscle relaxant, can be used to control tremors (55 to 220 mg/kg [25 to 100 mg/lb], IV) administered slowly to effect with a maximum dose of 330 mg/kg/d (150 mg/lb/d).^9,13 Guaifenesin (110 mg/kg [50 mg/lb], IV, repeated as needed) is a centrally acting skeletal muscle relaxant that may be used as an alternative to methocarbamol.⁹

The therapeutic effects of MPH are thought to result primarily from its inhibition of the presynaptic dopamine transporter; however, MPH may also affect serotonin levels in the CNS.¹³ Because of the potential of MPH to cause serotonin syndrome, APCC veterinarians and veterinary toxicologists consulting on MPH cases often recommend the use of cyproheptadine (1.1 mg/kg [0.50 mg/lb], q 4 to 6 h until signs have resolved), an antihistamine that also antagonizes serotonin.⁹ No published data are available on the efficacy of cyproheptadine to treat serotonin syndrome in dogs, but it has been used successfully in humans.²⁵

In addition to the previously described treatments, dogs should be monitored for hyperthermia and cooled as needed. Effective cooling methods include whole-body wetting, fans, and cooled IV fluids.²⁶ Chilled water should not be used to wet the dog as it can lead to vasoconstriction and decreased cooling.²⁶ Temperature should be monitored even after return to normothermia because hyperthermia from amphetamine toxicosis has been reported to return after cooling measures are ceased.¹⁷ This phenomenon may be more likely to occur following ingestion of ER formulations than after ingestion of IR formulations. Heart rate, blood pressure, ECG, fluid status, and acid-base status should all be regularly monitored and appropriately treated. Blood pressure measurements were not available in the APCC database for any dogs in this study, but hypertension has been associated with amphetamine toxicoses in dogs and would be anticipated as a potential clinical effect with MPH toxicosis.²⁷ Prazosin (0.5 to 2.0 mg/dog, PO) or other α-adrenergic receptor antagonists may be especially beneficial in reversal of hypertension associated with MPH toxicosis because these block the effects of catecholamines on postsynaptic α-1 receptors.^27,28 Other useful drugs for treating MPH-induced hypertension include sodium nitroprusside, hydralazine, and amlodipine.²⁷ The use of multiple antihypertensives (including propranolol) necessitates careful monitoring for the development of hypotension. Rhabdomyolysis has been known to result from muscular overstimulation in amphetamine poisoning, and the clinician should be aware of this possibility in dogs that have MPH intoxication.¹⁶ Aggressive fluid therapy should be initiated for patients with rhabdomyolysis.²⁷ Monitoring should continue for a minimum of 24 hours after ingestion of ER formulations and 12 hours after ingestion of IR formulations or until clinical signs have resolved in the patient.

Results of the study reported here revealed that even low doses of MPH can result in severe signs of clinical toxicosis; therefore, any dog that ingests MPH pills should be appropriately monitored and treated. Clinical signs in dogs with MPH toxicosis are diverse and may involve many organ systems. Most commonly detected clinical signs are behavioral and neurologic, but cardiopulmonary and digestive abnormalities may also develop with MPH toxicosis. Clinical signs of toxicosis following ingestion of ER MPH formulations are more likely to persist than those detected after ingestion of IR formulations, and prolonged patient monitoring may be necessary.