Tuesday, April 21, 2015

Is Tramadol An Effective Postoperative Analgesic in Dogs?


Postoperative pain control is a critical aspect of the care of surgical patients in veterinary medicine. Many drug types are available for postoperative analgesia such as opioids and non-steroidal antiinflammatories. Tramadol, a synthetic opioid, is a widely used analgesic in humans and has become popular for clinical use in dogs. It is an oral medication usually given at a dose of 2-4 mg/kg every 8-12 hours. It is frequently combined with a non-steroidal anti-inflammatory, such as carprofen, for postoperative analgesia. Side effects of tramadol include sedation, nausea, constipation, and seizures. Tramadol therefore is not recommended for dogs with seizure disorders.

Metabolism
Tramadol is metabolized by the liver to form O-desmethyltramadol, or the M1 metabolite.(1) This metabolite is also an active form of the drug. Pharmacokinetic studies have found that oral administration of tramadol results in adequate blood levels of the drug and its metabolite.(1)

Efficacy
Although rapidly gaining widespread use after introduction to the veterinary market, efficacy studies of the analgesic properties of tramadol have been slow to materialize. One study from several years ago separately evaluated morphine and tramadol for postoperative analgesia after ovariohysterectomy in dogs.(2) Using multiple parameters to evaluate pain, both drugs were found to be effective.  In another study, tramadol was compared to codeine and ketoprofen for analgesia after maxillectomy or mandibulectomy in dogs.(3) All drugs, including tramadol, were found to provide effective postoperative analgesia.

Conversely, more recent studies have found tramadol to compare poorly to other standard analgesics for postoperative pain. Carprofen was more effective than tramadol for postoperative pain in a series of dogs having enucleation.(4) Pain scores were monitored and dogs receiving tramadol were more likely to require rescue analgesics than those receiving carprofen. In another study, after TPLO for ruptured cruciate in 30 dogs, those that received firocoxib orally, alone or in combination with tramadol, had lower pain scores, lower rescue opiate administration, and greater limb function than dogs that received only tramadol.(5) Tramadol was also not effective in providing analgesia in an experimental study using an acute pain model in Beagles.(6)

These studies create a mixed and confusing message to veterinary clinicians about the efficacy of tramadol. Inherent to all pain studies is the difficulty in making objective assessments of postoperative pain in dogs, but well controlled studies using accepted methods of pain scoring should provide useful information. The conflicting results of clinical and experimental studies make it clear that tramadol alone as a postoperative analgesic may not provide the expected level of analgesia. This appears to be particularly true after procedures associated with high pain levels, such as in dogs having major orthopedic surgery.

Conclusions
Even in view of the studies showing lack of efficacy, tramadol’s advantages make it an attractive choice for postoperative analgesia. It is administered orally, is well tolerated by most dogs, and is felt by many clinicians to be a reasonable alternative for dogs in which NSAIDS are contraindicated. We routinely use tramadol in combination with carprofen for postoperative analgesia in dogs. In our clinical experience that combination provides effective analgesia even after orthopedic procedures such as TPLO. Tramadol alone is prescribed in those dogs that cannot take NSAIDS since there are few alternatives and tramadol is certainly better than no analgesic treatment.

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References
1. KuKanich, B. and Papich, M. G. (2004), Pharmacokinetics of tramadol and the metabolite O- desmethyltramadol in dogs. Journal of Veterinary Pharmacology and Therapeutics, 27: 239–246.

2. Mastrocinque, S. and Fantoni, D. T. (2003), A comparison of preoperative tramadol and morphine for the control of early postoperative pain in canine ovariohysterectomy. Veterinary Anaesthesia and Analgesia, 30: 220–228.

3. Martins TL1, Kahvegian MA, Noel-Morgan J, Leon-Román MA, Otsuki DA, Fantoni DT.
Comparison of the effects of tramadol, codeine, and ketoprofen alone or in combination on postoperative pain and on concentrations of blood glucose, serum cortisol, and serum interleukin-6 in dogs undergoing maxillectomy or mandibulectomy. Am J Vet Res. 2010 Sep;71(9):1019-26.

4. Cherlene Delgado, DVM, Ellison Bentley, DVM, DAVCO, Scott Hetzel, MS, and Lesley J Smith, DVM, DACVAA. Carprofen provides better post-operative analgesia than tramadol in dogs after enucleation: A randomized, masked clinical trial. J Am Vet Med Assoc. 2014 December 15; 245(12): 1375–1381.

5. Davila D1, Keeshen TP, Evans RB, Conzemius MG.
Comparison of the analgesic efficacy of perioperative firocoxib and tramadol
administration in dogs undergoing tibial plateau leveling osteotomy. J Am Vet Med Assoc. 2013 Jul 15;243(2):225-31.

6. Kogel B, Terlinden R, Schneider J. Characterisation of tramadol, morphine and tapentadol in an acute pain model in Beagle dogs. Vet Anaesth Analg. 2014 May;41(3):297-304




Sunday, April 12, 2015

Nasopharyngeal Polyps in Cats: Key words - stertor, traction, and bulla osteotomy

Nasopharyngeal (NP) polyps in cats are characterized by well-circumscribed solid masses that are found in the nasopharynx, tympanic bulla, and Eustachian tube.  They are benign and thought to be secondary to inflammation from bacterial or viral infections.  Similar polyps can also be present in the external ear canal.  Affected cats are usually young (less than 1 year) but all ages can be affected.

Clinical Signs

Presenting signs of nasopharyngeal polyps may vary depending on location. Inspiratory stertor is commonly found due to the fleshy mass just dorsal to the soft palate causing obstruction of the nasal passages. Stertorous breathing in cats should alert the clinician to a mass lesion in the nasopharynx since other causes, such as elongated soft palate, are uncommon in cats.

Signs of otitis media, such as Horner’s syndrome, head tilt, and pain may also be seen. (Fig. 1) 
Fig. 1: Right sided Horner's syndrome seen in a kitten with a
NP polyp. 
Polyps in the external ear canal can result in or be secondary to otitis externa causing head shaking, ear scratching, and malodorous otic discharge.

Diagnosis

A thorough oral examination should be performed. Sedation will probably be necessary since the polyp will likely be obscured by the soft palate. If the mass is large enough simple palpation of the soft palate with a finger may indicate a mass effect. Retraction of the soft palate with stay sutures or a spay hook, with the cat in dorsal recumbency, should expose the mass. (Fig. 2)
Fig. 2: NP polyp in a cat (arrow) adjacent to the soft palate (SP) The cat is in
dorsal recumbency.

Otoscopic examination should also be performed to look for extensions of polyps into the external ear canal. Cleaning of otic discharge and debris may be necessary to adequately expose the mass.

Differential diagnoses for nasopharyngeal polyps are lymphosarcoma, other types of  neoplasia, foreign body, or congenital anomaly of the pharynx or upper airway. In one study of nasopharyngeal disorders in 53 cats 49% of them were diagnosed with lymphosarcoma and  28% were diagnosed as polyps.(1)

Imaging

Skull radiographs with emphasis on the tympanic bulla may provide useful information. Affected cats may show radiographic signs of chronic otitis media such as bony proliferation of the bulla and increased soft tissue density within the bulla.(Fig. 3)
Fig. 3: Bony proliferation of the bulla (arrow) secondary to
a nasopharyngeal polyp in a cat.
However, radiographs of the bullae are not a very sensitive imaging test and significant changes may be present with normal appearing bullae on films.

CT scans are a more sensitive and diagnostic imaging modality for bulla disorders and are useful in cats with nasopharyngeal polyps or other bulla diseases. Increased soft tissue density is commonly seen in one or both bullae. (Fig. 4)
Fig. 4: CT scan of a cat with a NP polyp showing increased soft tissue density
within the bulla. (arrow)
In cases of severe infection or invasive neoplasia, lysis of the bulla may be seen. These findings are useful for preoperative evaluation of cats undergoing ventral bulla osteotomy, a recommended surgery for cats with nasopharyngeal polyps or other chronic middle or external ear disease.

Treatment

Traction

Surgical removal of the polyps is the most effective means of relieving clinical signs. Under general anesthesia the cat is placed in dorsal recumbency and a mouth speculum placed to allow exposure of the oral cavity and pharynx. The soft palate is retracted rostrally with either stay sutures or a spay hook. Gentle manipulation of this tissue is important since it is sensitive and prone to edema with manipulation.  Even under anesthesia many cats will exhibit discomfort while the soft palate is being manipulated. Once the polyp is exposed, grasp it with either stay sutures or Allis tissue forceps.(Fig. 5) Gentle but firm rostral and ventral traction is placed on the polyp and continued until the mass is removed. 
Fig. 5: NP polyp (arrow) being removed by traction.
The tissue frequently has a large round component that is connected to a tail that is the Eustachian tube portion of the polyp. Control hemorrhage with direct pressure on the affected pharyngeal tissues.

Bulla Osteotomy

To completely remove the polyp tissues, ventral bulla osteotomy is then performed. Which side to operate depends on the preoperative imaging or lateralizing clinical signs. If lateralization was not possible or if changes are seen bilaterally on imaging, both bullae are ostetomized to be sure of removing all remaining polyp tissues. Although most polyps are unilateral, the author recently treated a cat with bilateral polyps requiring osteotomy of both bullae.

Small fragments of polyp tissue are usually found in the tympanic bullae exposed by the ventral bulla osteotomy. (Fig. 6-7)
Fig. 6: Diagram of a ventral bulla osteotomy in a cat. Rongeurs are used to
remove the ventral aspect of the bulla and expose both compartments.
from: Boothe H. Surgery for otitis media and otitis internal.
From: Saunders Manual of Small Animal Practice3rd ed., Birchard and Sherding, editors. Elsevier, 2006, pg. 601.

Fig. 7: Bulla osteotomy in a cat with NP polyps. The ventral floor of the
bulla has been removed. Note the polypoid tissue filling the bulla cavity. (arrow)

It is important to expose both compartments of the bulla when performing the osteotomy (ventral-medial and dorso-lateral chambers). Care is taken not to injure components of the inner ear, located dorsally in the bulla, when doing polyp excision and curretage.  Save all tissues removed for histopathology and obtain samples from the bulla for culture and sensitivity.

Postoperative Care and Complications

Routine supportive care including analgesics and antibiotics are administered postoperatively. Antibiotic choice is guided by results of culture and sensitivity of samples obtained from the bullae.

Common complications after polyp removal are pharyngeal swelling and Horner’s syndrome due to injury to sympathetic nerves in the middle ear. Both of these problems are usually mild, short term in duration, and not requiring treatment. Recurrence of polyps is more likely if only the nasopharyngeal portion is removed. In a clinical study of 31 cats with nasopharyngeal polyps, 5 recurred postoperatively, 4 of which did not have a bulla osteotomy. (2)

References

1. HS Allen, J Broussard, and K Noone (1999) Nasopharyngeal diseases in cats: a retrospective study of 53 cases (1991-1998). Journal of the American Animal Hospital Association: November/December 1999, Vol. 35, No. 6, pp. 457-461. 
2. Kapatkin, AS, Matthiesen, DT, Noone KE. et.al. Results of surgery and long-term follow-up in 31 cats with nasopharyngeal polyps. J Am An Hosp Assoc 1990 Vol 26 No 4 pp. 387-392.