Introduction

Despite their ubiquity throughout North America, paintball ingestion is a relatively uncommon intoxication in veterinary medicine. Paintball ingredients vary between manufacturers but may include polyethylene glycol (high and low molecular weights), glycerin, and sorbitol—all high osmotically active agents encapsulated within a gelatin shell.^1–4 Although most paintballs are marketed as nontoxic, their ingestion can result in severe life-threatening hypernatremia and neurologic signs. The exact pathophysiology of hypernatremia following paintball ingestion is not completely understood. However, it has been proposed that the highly osmotically active components within paintballs drive the movement of water from the extracellular space into the gastrointestinal tract, rapidly increasing serum sodium levels.⁵

Polyethylene glycol (PEG) is a poly-ethyl compound that has many medical, industrial, and commercial uses.⁶ Within the medical field, PEG is primarily used as a laxative (i.e., Miralax^a, GoLYTELY^b) for colonoscopy preparation or constipation management because of its osmotic properties.^1,6,7 Generally, PEGs of high and intermediate molecular weights are considered nontoxic as they are minimally absorbed through the gut-blood barrier.¹ The number following the PEG name (i.e., PEG-3350) represents the average molecular weight (g/mol) of the solution.

This case report describes paintball toxicosis in a dog that developed severe neurological signs both before and after the development of acute hypernatremia that persisted beyond resolution of its electrolyte derangements. However, continued intensive care allowed for complete resolution of its clinical signs. The diagnosis, treatment, recovery, and follow-up are described. Informed consent was obtained from the owner, and the patient was managed according to contemporary standards of care.

Case Report

An 8 yr old 16.8 kg castrated male Cavalier King Charles spaniel dog was presented to the emergency hospital for an acute onset of an abnormal mentation and ataxia (Day 1). Approximately 1 hr before presentation, the patient developed ataxia and repeated head shaking and was reported to be eating grass. The owner administered hydrogen peroxide to induce vomiting, which was unsuccessful. He was subsequently presented to the emergency service for further evaluation of neurological signs.

Upon initial examination, the patient was quiet, alert, and responsive with an elevated body temperature (40.2°C). Notable abnormalities on physical examination included a grade II/VI left apical systolic heart murmur and a tense but nonpainful abdomen. The dog was tetraparetic and ataxic in all four limbs, had an inconsistent menace, and had progressive facial twitching. The rest of his neurologic examination was unremarkable.

Approximately 1 hr following presentation, the patient vomited bright fluorescent yellow material containing paintball shells. The owner confirmed the dog had access to the paintballs as early as 5 hr before the development of clinical signs. According to the Material Safety Data Sheet, the paintballs^c contained PEG-300, PEG-3350, glycerin, sorbitol, and oils within a gelatin casing (Figure 1).⁸ Baseline point-of-care blood work ∼2–7 hr after ingestion revealed a mild metabolic acidosis with respiratory compensation, mild hypernatremia (157 mmol/L), and hyperlactatemia (5.9 mg/dL). The patient received a 7 mL/kg warm water enema and was admitted to the intensive care unit for supportive care. The patient’s free water deficit (FWD) was calculated with the goal to decrease sodium by 6 mmol/L (157 to 151 mmol/L) over 12 hr (FWD, 401 mL); 5% dextrose in water (D5W^d) was started at 48 mL/kg/day. Full-strength 0.9% saline^e was concurrently provided as a maintenance solution at 47 mL/kg/day. Maropitant^f (1 mg/kg IV q 24 hr) was started.

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Four hours later, the dog became obtunded. A single tonic-clonic seizure occurred, which was treated with diazepam^g (0.5 mg/kg IV once). A repeat venous blood gas showed an unchanged sodium concentration of 157 mmol/L and an improved hyperlactatemia of 3.16 mg/dL. The dog’s blood pressure decreased to 92 mm Hg (Doppler^h) and he received a 10 mL/kg bolus of lactated Ringer’s solutionⁱ (LRS). A second tonic-clonic seizure occurred 4 hr later and midazolam^j (0.25 mg/kg IV once) was administered.

The next morning (Day 2), the patient continued to exhibit seizure activity characterized by paddling and full body tremors, which responded to midazolam^j (0.25 mg/kg IV once). Upon re-examination (10 hr following presentation), the patient was stuporous with a horizontal nystagmus, anisocoria, and mild continuous focal facial seizure activity. He had injected mucous membranes and harsh bronchovesicular lung sounds bilaterally with an increase in respiratory effort. His abdomen was enlarged and pendulous with palpable organomegaly. He was producing bright green liquid diarrhea. An indwelling urinary catheter (8-French 30 cm Foley^k) was placed, and the patient was provided with oxygen supplementation (fraction of inspired oxygen: 40%). Because of persistent seizure activity, a continuous rate infusion of midazolam^j was started at 0.3 mg/kg/hr.

Shortly thereafter, the patient’s neurologic status deteriorated to a comatose state. Repeat neurologic examination revealed an inconsistent palpebral reflex and an intermittently absent gag reflex. He was bradycardic (40 bpm), hypotensive (Doppler^h, 78 mm Hg), bradypneic (10 bpm), and hypoxemic (oxygen saturation [SpO₂] 85%) with short and shallow breaths. Because of rapid decline, the patient received midazolam^j (0.25 mg/kg IV once) and fentanyl^l (3 mcg/kg IV once) for emergent intubation with a 6-mm endotracheal tube. Supplemental oxygen was provided at 1 L/min and he was positioned with his head elevated at 30 degrees. The patient’s heart rate increased following intubation and he continued to spontaneously ventilate and oxygenate well without a requirement for mechanical ventilation. The patient was fluid resuscitated with a total of 30 mL/kg IV LRSⁱ and normotension was achieved.

The patient was started on ampicillin sulbactam^m (22 mg/kg IV q 8 hr) and enrofloxacinⁿ (10 mg/kg IV q 24 hr) for concerns of aspiration pneumonia, ondansetron^o (0.5 mg/kg IV q 8 hr), and continuous electrocardiogram monitoring, and an arterial line was placed in the right dorsal pedal artery for direct arterial blood pressure monitoring. A third venous blood gas (10.5 hr after presentation, 6 hr following the most recent venous blood gas) showed progressive metabolic acidosis, hypernatremia (170 mmol/L), and novel azotemia (blood urea nitrogen 40 mg/dL, creatinine 1.79 mg/dL). The combined 0.9% sodium chloride solution (NaCl^e) and D5W^d fluid therapy were discontinued, and the dog was transitioned to 0.45% NaCl^p as a single maintenance solution at 93 mL/kg/day. An 8-French nasogastric tube was placed to remove excessive gastric residuals and prevent regurgitation. Three-view thoracic radiographs revealed evidence of aspiration pneumonia, a dilated stomach with aerophagia, adequate placement of the nasogastric tube, and a large soft tissue structure within the fundus suspected to be a conglomeration of paintball material. Propofol^q (1–2 mg/kg IV titrated to effect) was administered and gastric lavage was performed to remove the remaining paintball material from the stomach. Postlavage abdominal radiographs showed significant improvement in the gastric dilation with minimal persistent radio-opaque material in the stomach and proximal duodenum. A continuous infusion of metoclopramide^r was started at 2 mg/kg/day. Levetiracetam^s (30 mg/kg IV q 8 hr) was started for seizure prophylaxis and the midazolam^j infusion was weaned off. The dog maintained adequate spontaneous ventilation but remained comatose and intubated without sedation.

Blood work was repeated 6 hr following intubation (16 hr after presentation) and showed resolution of the azotemia (blood urea nitrogen 21 mg/dL, creatinine 0.88 mg/dL) and hyperlactatemia (0.55 mg/dL); however, the sodium concentration continued to increase (172 mmol/L). The dog’s FWD was recalculated with the goal to decrease sodium by 17 mmol/L back to its approximate baseline (155 mmol/L) over 12 hr (FWD, 1106 mL); D5W^d was started at 132 mL/kg/day and the 0.45% NaCl^p was discontinued. Five hours later, the dog’s sodium decreased to 165 mmol/L.

The following morning (Day 3), the dog became hypertensive (direct arterial systolic pressure 180–200 mm Hg) and his heart rate decreased to 60–70 bpm. The dog received a single injection of butorphanol^t (0.3mg/kg IV once) to rule out an increasing level of consciousness while intubated with no change in blood pressure. Repeat blood work (6 hr after prior sampling, 11 hr after FWD calculation) showed a normal sodium concentration of 145 mmol/L, 10 mmol/L below the previously established target of 155 mmol/L. The patient’s fluids were changed from 132 mL/kg/day of D5W^d to 66 mL/kg/day of D5W^d and 66 mL/kg/day of 0.45% NaCl^p with the goal of preventing further decline in sodium concentration. Persistent systemic hypertension and bradycardia were concerning for a Cushing reflex. Mannitol^u (0.5 g/kg IV once) was slowly administered given the concern for increased intracranial pressure. After the mannitol injection, systolic blood pressure decreased to 150 mm Hg and the dog’s pupils became equal in size and responsive to light. He began coughing and swallowing and was extubated 22 hr following the initial endotracheal intubation. The dog was oxygenating appropriately on room air and oxygen supplementation was discontinued. He remained quiet with intermittent periods of dysphoria and began making attempts to ambulate throughout the day. His sodium normalized to 142 mmol/L (Figure 2) and he was maintained on a combination of LRSⁱ and 0.45% NaCl^p for the remainder of his hospitalization. Enteral nutrition was started via the nasogastric tube at 25% resting energy requirements.

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The following day (Day 4), the dog’s mentation, ambulation status, and gastrointestinal signs continued to gradually improve, and he developed a good appetite. He was successfully discharged the next day (Day 5) with a normal mentation and stable electrolytes and eating well. Two weeks after discharge, the owners reported that the dog was bright and alert with no residual neurological signs and normal blood parameters on recheck blood work.

Discussion

This report describes the successful management of a case of paintball toxicosis associated with PEG ingestion that developed severe neurologic effects both before and after severe hypernatremia. Among the scarcity of veterinary literature pertaining to paintball toxicosis in dogs, seizures and coma are reported as possible sequelae, although their clinical course and potential for resolution has yet to be reported.^5,9 This patient developed an early onset of seizures in the face of only mild hypernatremia and ultimately survived despite severe neurological deterioration requiring intubation and intensive supportive care. This is the first veterinary report to highlight not only these potential life-threatening consequences associated with “nontoxic” paintball intoxication but also its successful management and complete neurologic recovery in a comatose dog.

Although market available paintballs are sold as “nontoxic,” paintball ingestion has been reported to result in life-threatening hypernatremia and subsequent neurologic effects.⁵ Paintballs contain high concentrations of osmotically active agents, in particular PEG, that can result in significant free water shifts from the extracellular space into the gastrointestinal lumen following exposure to a high alimentary dose.^8,10 This hypotonic and isotonic water loss into the gastrointestinal tract can markedly increase plasma osmolality and serum sodium concentration, ultimately resulting in hypernatremia, diarrhea, and volume depletion.^11,12 Comparatively, PEG laxative solutions (except for sodium phosphate preparations) are iso-osmotic and low in sodium concentration after dilution with large volumes of water.^7,10 Consequently, hyponatremia is a commonly reported adverse effect in human patients after use of PEG-3350-containing laxative products.¹⁰ The sodium concentration and sodium containing ingredients within the ingested paintballs in this case are not known; therefore, excessive direct sodium loading contributing to hypernatremia cannot be ruled out.

The neurologic signs associated with hypernatremia are a result of the osmotic movement of intracellular fluid out of neurons leading to cell shrinkage, reduction in cerebral water content and volume, swelling of cerebral vasculature, and focal hemorrhage.^13–15 The severity of clinical signs is associated with both the rate and the magnitude of sodium increase from baseline, with an onset of clinical signs generally developing once sodium concentrations exceed 170 mmol/L.^13–17 Clinical signs of severe hypernatremia include obtundation, vomiting, lethargy, weakness, and ataxia, with more severe signs of coma, seizures, and death generally arising once sodium concentrations exceed 180 mmol/L.^13–17 In this case, the patient was presented with neurologic signs (decreased mentation, ataxia, tremors) despite only mild hypernatremia (157 mmol/L). He went on to develop tonic-clonic seizures within 4 hr of admission; however, blood work at the time showed an unchanged sodium concentration well below the threshold in which we would typically expect such severe neurologic signs (i.e., >180 mmol/L).^13–17

The primary goal in the treatment of hypernatremia involves replacing free water over a calculated period to facilitate decreasing the sodium by 0.5 mmol//L/hr, particularly in chronic cases.^15–17 In this case, venous blood gas analysis was performed every 4–6 hr for frequent monitoring of the patient’s hypernatremia. However, it is important to note that sodium concentrations should ideally be re-evaluated no less than every 4 hr, as ongoing unmeasured losses are not accounted for in a single FWD calculation and frequent changes to the fluid therapy plan are often required. In acute hypernatremia, as exhibited in this case report, faster corrections in sodium concentration may be tolerated owing to lack of compensatory idiogenic osmoles.^15–17 However, rapid overcorrection of chronic hypernatremia may lead to cerebral edema and an elevation in intracranial pressure.^15–17 The hypertensive and bradycardic episodes (i.e., Cushing reflex) exhibited by this patient may have been a result of cerebral edema formation secondary to rapid sodium correction, although other contributors such as the rapid excretion of exogenous osmotically active paintball ingredients or direct cerebral injury are also possible, particularly given the acute nature of the hypernatremia. The true origin of the hypertensive events in this patient remains unknown, although a partial response to mannitol was noted.

Despite rapid correction of the patient’s sodium derangement, his mentation did not improve sufficiently to allow for extubation until ∼7 hr following resolution of the hypernatremia. Acute hypernatremia has the potential to result in intracranial hemorrhage secondary to rupture of cerebral vessels and decreased cerebral volume, which may have contributed to this lag in neurologic improvement.^11–17 Interestingly, of the paintball ingestion cases in dogs handled by the American Society for the Prevention of Cruelty to Animals Animal Poison Control Center between 1998 and 2003, ataxia was reported in 45% of dogs; however, only 22% had documented hypernatremia.^5,18 This raises the theory that hypernatremia may not be the sole pathophysiologic derangement contributing to the patient’s neurologic defects. Although there are few reports of toxicosis associated with low-molecular-weight PEG (<400 g/mol), it has been reported that these lower weight compounds may be readily absorbed into circulation.^19,20 In previous reports involving both people and rodents, oral and transdermal absorption of low-molecular-weight PEG and metabolites including ethylene glycol were measured in systemic circulation.¹⁹ Among these reports, side effects following systemic absorption included narcosis, respiratory paralysis, and death.^19,20 It is possible that the systemic absorption of the low-molecular-weight PEG component of the paintballs, its contribution to serum osmolality, and/or its metabolism into ethylene glycol may or may not have contributed to the severity of neurologic signs in this case despite only mild hypernatremia at the time of onset. Ultimately, direct conclusions about the cause of the patient’s lag in neurologic improvement after normalization of sodium cannot be made.

Conclusion

There are several limitations regarding this case report. As the patient gained access to a previously opened box of paintballs, an exposure dose of ingested paintballs was unable to be calculated. The paintballs were not submitted to a reference laboratory for analysis of their sodium concentration and osmolality. This analysis would have been beneficial to rule out hypernatremia secondary to excessive gastrointestinal absorption of sodium. Blood and urine samples from the patient were not obtained throughout hospitalization for laboratory analysis for PEG, ethylene glycol, or oxalic acid concentrations. Therefore, we cannot confirm the presence of these compounds and their potential effects on the patient’s neurologic signs. Gastric decontamination was also quite delayed in this case, which may have contributed to the severity of the clinical signs despite aggressive fluid therapy. Given the paucity of literature regarding the systemic effects of low-molecular-weight PEG, it remains difficult to draw definitive conclusions about its contribution to hypernatremia, neurologic effects, and other systemic abnormalities. Finally, advanced imaging such as computed tomography or MRI was not performed to confirm other causes for his comatose state including intracranial hemorrhage.