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A 3-year-old Labrador retriever was presented to the Western College of Veterinary Medicine for a tibial plateau levelling osteotomy. While performing a pre-operative epidural, thiopental was inadvertently administered into the epidural space. Treatment included epidural saline flushing and intravenous methylprednisolone sodium succinate. No neurologic deficits were detected.
Injection épidurale accidentelle de thiopental chez un chien. Un Labrador Retriever de 3 ans a été présenté au Western College of Veterinary Medicine pour une ostéotomie de nivellement du plateau tibial. Pendant la réalisation d’une épidurale préopératoire, le thiopental a été administré par inadvertance dans l’espace épidural. Le traitement a inclus un lavage épidural avec une solution saline et du succinate sodique de méthylprednisolone. Aucun déficit neurologique n’a été détecté.
(Traduit par Isabelle Vallières)
A 3-year-old, 45-kg, castrated male, Labrador retriever was presented to the Western College of Veterinary Medicine Veterinary Teaching Hospital for right pelvic limb lameness. A cranial cruciate ligament rupture was diagnosed after physical examination and radiography. The rest of the physical examination, as well as a complete blood (cell) count and serum biochemical panel, were unremarkable, and the dog was scheduled for a tibial plateau levelling osteotomy (TPLO) 7 d later.
The dog was sedated with acepromazine (Atravet; 10 mg/mL, Ayerst Laboratories, Montreal, Quebec), 0.05 mg/kg, IV, and hydromorphone (Hydromorphone; 10 mg/mL, Sabex, Boucherville, Quebec), 0.1 mg/kg, IM. An IV catheter was placed in a cephalic vein for fluid therapy (Normosol R; Hospira Healthcare Corporation, Montreal, Quebec), 10 mL/kg/h and anesthesia was induced with thiopental 2.5% IV (Pentothal; Hospira Healthcare Corporation), 7 mg/kg. Anesthesia was maintained with isoflurane in 100% oxygen using a circle breathing system.
Additional radiographs of the right hind limb were performed to allow accurate measurement of the angle of the tibial plateau. The dog was clipped and aseptically prepared for an epidural injection of bupivacaine HCl 0.75% (Marcaine, Hospira Healthcare Corporation), 1 mg/kg, and morphine sulfate (Morphine HP®25, Morphine Sulfate Injection USP; Sandoz Canada, Boucherville, Quebec), 0.1 mg/kg. Placement of the epidural needle in the lumbosacral space was confirmed by loss of resistance to injection of air. A syringe, presumed to contain the morphine and bupivicaine, was then attached to the needle. During the injection, it was noted that 2 mL of the remaining 5 mL of thiopental 2.5% (1.1 mg/kg) from the IV induction dose had been inadvertently administered rather than the bupivicaine/morphine mixture. The epidural needle was replaced with a new spinal needle, and 5 mL of 0.9% saline (Sodium Chloride Injection USP 0.9%; Hospira Healthcare Corporation) was injected over 1 min in an attempt to dilute the solution within the epidural space. The dog’s cardiovascular parameters remained stable, and a 20-gauge epidural catheter (Arrow Epidural Catheterization Set with FlexTip Plus Catheter for Pediatric Lumbar Placement; Arrow International, Reading, Pennsylvania, USA) was placed in the lumbosacral space and inserted 2.5 cm into the epidural space. A 10-mL volume of 0.9% saline was injected through a filter (Epidural Flat Filter with Luer Lock fitting; Smiths Medical Trademarks, Portex, Keene, New Hampshire, USA). Correct positioning was confirmed radiographically, and the dog was allowed to recover from anesthesia. During recovery, 40 mL of 0.9% saline were administered by syringe driver into the epidural space over 30 min, and the epidural catheter was removed. Methylprednisolone sodium succinate (Solu-Medrol; Pfizer, Markham, Ontario), 30 mg/kg, IV, was administered slowly, and the dog was maintained on IV Normosol R. The dog recovered uneventfully with no evidence of pain or neurologic impairment. The dog was observed in hospital overnight, and the surgery was postponed for 1 wk.
The following week, a TPLO was performed using intraarticular bupivicaine for analgesia; anesthesia and surgery were uneventful. The dog recovered well from surgery, and 2 mo later showed no signs of neurologic impairment.
Accidental epidural administration of thiopental, or any drug not intended for epidural use, has not been reported in the veterinary literature. In human medicine, however, multiple cases have been reported. A literature review identified numerous drugs inadvertently injected epidurally, including thiopental, methohexital, vecuronium, midazolam with fentanyl, morphine with dextrose, ephedrine, cefazolin, gentamicin, amoxicillin-clavulanic acid, potassium chloride, magnesium sulphate, total parenteral nutrition, Intralipid infusion, phenol containing ranitidine, ether, and paraldehyde (1). Complications that have been reported in humans as a result of accidental epidural drug administration include respiratory depression with remifentanil (2), sensory blockade, muscle spasms, and hypertension with potassium chloride (3), and a significant decrease in blood glucose level with insulin (4).
There are several case reports in humans that involved accidental epidural thiopental administration (5–7). In these reports, between 6 and 20 mL of 2.0% or 2.5% thiopental were injected epidurally into 4 human patients. Two awake patients experienced mild discomfort during the injection and sedation that followed (5,7). However, no neurologic complications were reported in any patient (5–7). Treatments upon recognition of the epidural thiopental injection have included aspiration from the epidural catheter (6), epidural injection of bupivicaine and lidocaine (5,7), epidural epinephrine (5), normal saline infusion through an epidural catheter (5–7), and epidural methylprednisolone (5).
Thiopental has a pH of 10.7 (7) and is therefore irritating to tissues. After perivascular administration it has been reported to cause an arteriovenous fistula in a dog (8), and has also caused vasoconstriction of cerebral and extra-cerebral arteries in dogs in vitro, which is potentially mediated by calcium ion influx (9). In rats, both vasoconstriction (muscle and fat) and vasodilation (intestine) have been observed in vivo (10). The vascular effects of thiopental may depend on the species and organ, and the actual in vivo effect of the drug on canine epidural vasculature is unknown. The potential for significant tissue inflammation, ischemia, and necrosis was the main concern after the epidural injection in our patient.
The recommended treatment for perivascular injection of thiopental is infiltration with a local anesthetic (11,12) or saline (12). Saline is used to dilute the thiopental, but the exact mechanism of the presumed beneficial effect of local anesthetics is unknown. Lidocaine and bupivicaine have pHs of 6.5 and 5.8, respectively, which when mixed with thiopental, will decrease the pH (7), and possibly limit alkali damage. However, decreasing the pH of thiopental, a weak acid, will in theory increase the unionized fraction and therefore the fraction available for absorption (13), which would be undesirable. The formation of precipitate when thiopental is added to a lidocaine-bupivicaine mixture may be an alternative mechanism by which absorption of the thiopental is limited (14). Local anesthetics also cause vasodilation (15), which may help counteract thiopental mediated vasoconstriction. It should be emphasized that use of local anesthetics and/or saline after accidental epidural thiopental administration is not based on extensive research.
In our case, epidural flushing with saline alone was performed, and the dog was allowed to recover from anesthesia so that he could be assessed for neurologic deficits. Saline has been used successfully in the medical field for treatment of accidental thiopental injection (5–7), and cerebrospinal lavage appears to be an effective treatment in cases of inadvertent intrathecal injection of local anesthetics secondary to epidural catheter misplacement in humans (16,17). Local anesthetics were not injected epidurally because of the absence of controlled studies documenting their benefit. In addition, the induction of sensory and motor blockade would have made immediate neurologic assessment difficult.
Methylprednisolone sodium succinate as a treatment for acute spinal cord injury is a commonly used but controversial practice (18). One rationale for its use as a neuroprotective agent lies in its ability to decrease lipid peroxidation (19) that may contribute to free radical formation after acute spinal cord injury (20). Studies in cats using intravenous high dose methylprednisolone sodium succinate shortly after experimental traumatic injury to the spinal cord have shown a decrease in the spread of tissue damage (21), as well as clinical neurologic improvement (22). One study in dogs, however, does not support these beneficial effects (23). As we were concerned that acute inflammation and ischemia secondary to vasoconstriction could occur, methylprednisolone sodium succinate was administered in an attempt to minimize these potentially detrimental effects.
Since no scientific studies have examined the necessity or efficacy of the reported treatments for epidural thiopental injection, and no veterinary reports exist, our patient was treated based on documented experiences of human anesthesiologists and recommendations for treatment of acute spinal cord injury, however controversial. Possible reasons our patient showed no adverse effects were the small volume (2 mL, 1.1 mg/kg) and low concentration (2.5%) of thiopental that was injected, as well as immediate dilution with saline. The lipophilic nature of thiopental may allow rapid systemic uptake of the drug through epidural vessels.
Error rates in human anesthesiology have been reported at 1:133 (24) and 1:880 (25), with 44% of errors in the latter study being a “syringe swap.” Herein, a “syringe swap” led to accidental epidural thiopental administration, despite a color-coded drug label system in place at the Veterinary Teaching Hospital that was used in this case. In human medicine, colored syringe labels have not eliminated these types of mistakes (25). Investigation into the error rate in veterinary anesthesia and the measures taken to avoid errors would be beneficial. Although no adverse effects were seen in this patient, the case emphasizes the necessity of double-checking drug labels to avoid potential deleterious effects of administration of drugs by the wrong route.
The authors thank Dr. Matt Johnson for his role as the primary surgical clinician, Dr. Cindy Shmon for her role as faculty surgeon and for her assistance with editing, and Dr. Tanya Duke for her role as faculty anesthesiologist and for assistance with editing. CVJ
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