Introduction

Non-steroidal anti-inflammatory drugs (NSAIDs) are widely used for analgesia in the peri-operative period with a recent UK survey showing that around 98% of dogs and cats receive NSAIDS for routine procedures such as neutering peri-operatively.¹ There are also many studies that support the analgesic benefit of administering a NSAID for acute pain relief after different types of surgery. However, NSAIDs are not without side effects, and although some risk factors for adverse events have been identified, it remains difficult to identify in advance which individual patient may develop side effects as a result of peri-operative NSAID administration. In order to reduce the likelihood of adverse effects it is important to understand the mechanism of action of NSAIDs and their potential side effects on organ function. This knowledge, combined with an understanding of factors that may increase the risk of side effects in an individual patient can be used to determine which patients should receive NSAIDs peri-operatively and overall reduce the likelihood of NSAID related adverse events.

What Are the Advantages of NSAID Administration Peri-operatively?

The clear and obvious advantage of NSAID administration in the peri-operative period is analgesia with NSAIDs making a valuable contribution to both preventive and multi-modal analgesia. Preventive analgesia aims to decrease the impact of the nociceptive barrage associated with noxious stimuli in the peri-operative period, in particular with a focus on decreasing the development of peripheral and central sensitisation. Multi-modal analgesia refers to the use of different classes of analgesic drug in combination, so that the pain pathway is obtunded at multiple different receptors and targets, overall increasing efficacy of the analgesic protocol compared to using a single class of analgesic drug in isolation. Multi-modal techniques may also allow a reduction in dose of each individual class of drug and, therefore, reduce side effects; a factor that may be particularly pertinent for opioids where sedation or dysphoria and nausea can be problematic in the post-operative period. Multi-modal analgesia techniques incorporating opioids and NSAIDs are widely used in dogs and cats undergoing routine procedures such as neutering and there is good evidence to support their efficacy over unimodal techniques in these species.

NSAIDs are also the only class of drug that is licensed to be administered by owners in the home environment after surgery. The optimal time duration for the administration of analgesics after different types of surgery is currently unknown. There is a trend in the UK for the administration of tramadol instead of or in combination with NSAIDs peri-operatively but it should be noted that the evidence for the efficacy of oral tramadol is very limited;² therefore, tramadol should not be used as a NSAID substitute unless NSAIDs are contra-indicated in a particular patient. Therefore, peri-operative NSAIDs play a pivotal role in the provision of post-operative analgesia following surgery.

What Are the Disadvantages of NSAID Administration Peri-operatively?

The major disadvantage of NSAID administration in the peri-operative period is the risk of adverse effects. Probably the most important consideration for NSAID administration is whether there is a significant risk of hypotension during anaesthesia, because of the potential for renal ischaemia and acute kidney injury when production of renal prostaglandins is inhibited in the face of reduced renal blood flow. One might argue that hypotension is always a risk factor during anaesthesia and, therefore, NSAID administration should always be delayed until after anaesthesia when the patient is awake and likely to be normotensive but this might be disadvantageous in terms of optimising analgesia. The author takes a pragmatic approach to this conundrum. NSAID administration is delayed until after anaesthesia and surgery if there is considered to be a greater likelihood of hypotension during anesthesia, whereas NSAIDs are administered pre-operatively to healthy patients undergoing routine surgery. This approach should maximise the analgesic benefit of NSAIDs in healthy patients while avoiding adverse events in patients that are cardiovascularly unstable or patients where significant blood loss is anticipated.

Monitoring and supporting blood pressure during anaesthesia: When administering a NSAID before anaesthesia and surgery it is best practice to monitor and support blood pressure during anaesthesia to ensure that animals do not become hypotensive during the peri-operative period (mean arterial blood pressure [MAP] <60 mm Hg).

What about patients with chronic kidney disease? There is some evidence to suggest that prostaglandins produced in the kidney via cyclo-oxygenase enzyme are not important in maintaining renal blood flow and GFR under conditions of euvolemia and normotension in cats and dogs. However, it is also known that COX expression in the kidney is altered in chronic kidney disease (CKD) in cats and dogs and in humans with CKD there is an increased risk of nephrotoxicosis from NSAIDs.³

A recent study in cats with IRIS stage 2–3 CKD given meloxicam found no effect of meloxicam administration on GFR suggesting that maintenance of GFR was not dependent on cyclo-oxygenase derived prostaglandins⁴ and studies in cats with osteoarthritis administered meloxicam have not shown a detrimental effect of chronic NSAID (meloxicam) administration on renal parameters or longevity.^5,6 However, in these studies, cats were not anaesthetized and blood pressure was presumably maintained within normal limits; therefore, it is difficult to extrapolate these findings to an anaesthetized patient where hypotension is common.

The author errs on the side of caution in terms of peri-operative NSAID administration to cats and dogs with CKD; in the peri-operative period adequate analgesia can usually be provided with opioids or adjunctives such as ketamine. A NSAID can be considered once the animal is normotensive and fully recovered from anaesthesia, although complete data on the safety of NSAIDs in CKD patients are currently lacking and this must be considered in the decision-making process.

Animals undergoing gastro-intestinal surgery: There are no data describing the clinical effects of NSAIDs on the healing of the gastrointestinal tract after surgery in dogs and cats. However, given that cyclo-oxygenase derived prostaglandins are important in angiogenesis and healing in the GI tract it would seem sensible to avoid NSAID administration to cats and dogs undergoing GI surgery. At the author’s institution, in dogs, such cases are commonly administered paracetamol intravenously, although it is important to be aware that the intravenous preparation of paracetamol is not licensed in dogs and there no data to compare the safety of paracetamol with NSAIDs in animals with GI disease. Similarly, the author would avoid NSAID administration to dogs and cats with pre-existing ulcerative GI disease that may be at a higher risk of GI perforation compared to the healthy animal.

Animals with disorders of haemostasis: NSAIDs with effects on the COX-1 enzyme will decrease production of thromboxane A2 in platelets, therefore, it is prudent to avoid NSAID administration to animals with disorders of haemostasis in the peri-operative period. Animals undergoing orthopaedic surgery: The author considers that there is currently insufficient clinical evidence to indicate that NSAIDs should be withheld from animals undergoing orthopaedic surgery involving bone healing and that NSAIDs should be used peri-operatively as part of a multi-modal analgesia technique.

Timing of NSAID Administration in the Peri-operative Period

NSAIDs that are licensed for administration in the peri-operative period can be given before surgery at around the time of premedication, during surgery or post-operatively once the animal is fully recovered from anaesthesia and normotensive.

There is some evidence that administering NSAIDs pre-operatively provides superior analgesia and reduces secondary hyperalgesia, a cardinal sign of central sensitisation, after surgery, compared with post-operative administration (Lascelles et al. 1998). This would suggest that the optimal time of administration in terms of pain-relief is pre-operatively. However, side effects should always be considered and if there is concern over blood pressure management during anaesthesia then administration of any NSAID should be delayed until the animal is normotensive and fully recovered from anaesthesia.

References

1.  Hunt JR, Knowles TG, Lascelles BD, Murrell JC (2015). Prescription of perioperative analgesics by UK small animal veterinary surgeons in 2013. Vet Rec. 176:493.

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

3.  Gooch K, Culleton B, Manns B, Zhang J, Alfonso H, Tonelli M, Frank C, Klarenbach S, Hemmelgarn BR (2007). NSAID use and progression of chronic kidney disease. Am J Med. 120:281–287

4.  Surdyk KK, Brown CA, Brown SA (2013). Evaluation of glomerular filtration rate in cats with reduced renal mass and administered meloxicam and acetylsalicylic acid. Am J Vet Res. 74:648–51.

5.   Gowan RA, Baral RM, Lingard AE, Catt MJ, Stansen W, Johnston L, Malik R (2012). A retrospective analysis of the effects of meloxicam on the longevity of aged cats with and without overt chronic kidney disease.  J Fel Med Surg. 14:876–81.

6.  Gowan RA, Lingard AE, Johnston L, Stansen W, Brown SA, Malik R (2011). Retrospective case-control study of the effects of long-term dosing with meloxicam on renal function in aged cats with degenerative joint disease. J Fel Med Surg. 13:752–61.