- Email: [email protected]
Post operative analgesic actions of flunixin in the cat
J. vet. Anaesth. Vol. 23(2) (1996)
Post operative analgesic actions of flunixin in the cat D. Fonda Clinica Chirurgica Veterinaria, Universita' degli Studi di Milano, Celoria 10, 20133 Milano, Italy
SUMMARY
MATERIALS AND METHODS
The post operative analgesic and sedative effects of flunixin (1 mgkg bwt) iv were investigated for the first 90 min post surgery in 20 cats undergoing a variety of surgical procedures. The results were compared with those obtained in another 20 cats, subjected to similar anaesthetic and surgical procedures, but treated with pethidine, 3 mgkg bwt iv. Post operatively, the analgesic effect of flunixin was shown to be adequate and its administration safe, so that it may reasonably be included among possible post operative analgesic treatments of choice in cats.
All the cats were referred to the Surgical Department of the University of Milan. They were healthy and randomly assigned to the FLX or PDT group. Details of gender, age, weight and duration of anaesthesia are shown in Table 1. The cats were scheduled for a variety of surgical procedures (Table 2). The anaesthetic regimen included premedication with acepromazine (0.25 mgkg bwt) and atropine (0.06 mgkg bwt), given together im, followed after 20 min by ketamine (20 mgkg bwt im) and endotracheal intubation. Anaesthesia was maintained with halothane in oxygen (100%) using a non-rebreathing system (Mapleson C). The cats were given the analgesic drug, flunixin meglumine (1 mgkg bwt iv) or pethidine hydrochloride (3 mg/kg bwt iv), when the halothane was turned o f f . A visual analogue scale (100 mm) was used to measure the pain score post operatively (Reid and Nolan 1991). A score of zero was applied to those animals which were pain free and a score of 100 to those which showed maximum pain. A score of more than 60 points was taken to indicate insufficient analgesia and the need for further analgesic drug. Observations for pain score were carried out for each cat by 3 veterinary students, who were unaware which analgesic drug had been administered. The graphic V.A.S. scale was recorded at 15 min intervals for 1.5 h. Pain assessment involved observation of the response to stimulation of the patient (Lloyd-Thomas 1990). The stimulus was applied either by movement of the treated area or limb in orthopaedic surgery or by finger pressure on the surgical wound. Other clinical changes, including heart and breathing rates, and behavioural alterations which occurred after pain stimulation were recorded. An attempt was made to separate the sedative effect from analgesia. To follow the scoring system previously reported in the dog (Young et al. 1990), evaluation of sedation in the cats was performed on the basis of 9 clinical variables: spontaneous position, placement on side, jaw tone, response to noise, attitude, pedal reflex, palpebral reflex, response to tongue traction, and anal reflex. A sedation score, from a maximum of 34 points in an anaesthetised, sleeping animal, to 0 points in an awake, normal cat, was recorded at the same time intervals. Because of the potential for hypotension at high doses of pethidine, arterial blood pressure was monitored indirectly (Sphygmomanometer Neonatal BP- 107, Nippon Colin) at
INTRODUCTION Advances in the understanding of the pathophysiology of pain (Bonica 1992), together with a renewed awareness of the importance of animal welfare (Rollin 1987), have led to improved post surgical pain control. However, until recently these developments have only been applied in a limited manner to cats. Opiate drugs have had restricted use because of excitement in the case of overdose and of imagined respiratory depression (Hall and Clarke 1991). The older non-steroidal anti-inflammatory agents (NSAIDs) such as phenylbutazone and acetaminophen have not been recommended as analgesics for cats because of toxicity and other untoward effects. Use of the newer NSAIDs, such as meclofenamic acid, naproxen, fenoprofen, ibuprofen, indomethacin, has also been restricted (Dodman 1992). Considerations such as these account for the general failure to provide adequate post operative pain relief in cats. Flunixin (FLX) meglumine is a non-steroidal antiinflammatory drug. It was considered to be toxic in cats by Krohne and Vestre (1989), although no references were given to explain this supposed toxicity (Cribb 1992). In later studies the main pharmacokinetic parameters of FLX were determined in the cat after a single oral or iv administration and no clinical signs of toxicity were seen (Lees and Taylor 1991; Taylor et al. 1991; Taylor et al. 1994). In the present study, the analgesic and sedative effects of flunixine meglumine (1 mgkg bwt iv) were evaluated in 20 cats. Comparison was made with another 20 cats, which underwent similar anaesthetic and surgical procedures, but were given pethidine hydrochloride (PDT), 3 mgkg bwt iv. A preliminary report, with fewer cases and different surgical procedures, has been published (Fonda 1993). 52
J. vet. Anaesth. Vol. 23(2) (1996)
TABLE 3: Pain scores, expressed as mean t sem at different times after the injection of the analgesic drug (time 0)
TABLE 1: Details of the cats included in the study Group 1 (n=20) Flunixin
Group 2 (n=20) Pethidine
10110
1218
Age (mean) range
2y 5m 4m-12y
l y 5m 1.5-4y
bwt (mean) range
3.4 kg 1-7 kg
3 kg 250 g-6 kg
53 min 12-133 min
62 rnin 18-1 20 rnin
Maledfemales
Anaesthesia time (mean) range
Time
Flunixin
Pethidine
15' 30' 45' 60' 75' 90'
7.8 (k2.8) 7.9 (k2.1) 13.3 (k2.9) 15.9 (k2.9) 16.8 (k2.7) 20.8 (k2.6)
1.9 (k0.2) 5.1 (k1.l) 8.9 (kl.8) 12.7 (k2.5) 19.4 (k4.2) 23.3 (k4.9)
P
<0.05 NS NS NS NS NS
TABLE 4: Sedation scores expressed as mean t sem at different times after the injection of the analgesic drug (time 0) Time
TABLE 2: Number of cats undergoing each surgical procedure Surgical procedure Fracture repair Ostectomy Ophthalmic surgery: conjuntival flap keratectomy ocular enucleation third eyelid excision Soft tissue surgery: cleft palate repair npl excision Abdominal surgery: cystotomy ovariectomy
Group 1 Flunixin
Group 2 Pethidine
9
9 2 4
4 (2) (-) (11 (1) 5
(1) (2) (1) 4
(2) (3) 2
15' 30 45 60 75' 90
(-1
29.7 25.4 21.6 19.7 16.4 12.9
(* 0.9) (* 1.4) (* 1.8) (i1.7) (* 1.5) (k 1.5)
Pethidine 31.6 (k 0.7) 28.8 (k 1.1) 24.7 (k 1.4) 23.0 (k 1.3) 20.1 (k 1.3) 16.3 (* 1.1)
P
NS
<0.005 <0.005 <0.005 <0.005 ~0.005
at 15 min with similar pain scores in both groups during,the remaining 75 min (Table 3). In the FLX group, one cat showed pain scores of 50 and 51 after conjunctival flap construction, but it was not considered to need additional, opioid analgesia. In the same group, in spite of low pain scores, 2 cats occasionally attemped to rub their mouths with their paws after cleft palate repair. No other undesiderable responses were observed. FLX treatment produced lower sedation scores than PDT, with statistical significance at all time points after 15 rnin (Table 4). In the 5 cats in which blood pressure was monitored, significant differences were seen in heart and respiratory rates during the first 45 rnin between the 2 drug groups, with higher values in cats injected with flunixin (Table 5). The' difference between the values for systolic, mean and diastolic pressure for the 2 groups did not achieve statistical significance, except at one time point for diastolic pressure (Table 6).
(-1 (1) (3)
1 (2)
Flunixin
(-1 (11
the beginning of this study in 5 cats given pethidine and for comparison in another 5 cats given flunixin. The occlusion cuff was always placed over the medial artery above the carpal joint. Sphygmomanometry allowed the recording of systolic, mean and diastolic pressures and heart rate. Breathing rate was recorded by direct observations over 30 s. Mean (+ sem) values on the scores at each time point were calculated. Variances of the 2 groups were compared using a test for normal random variables (F for P<0.05). A 2tailed 2 samples t-test was used to determine significant differences between the groups. P<0.05 was considered significant. In the comparison of the sedation scores, which were deemed to be non-parametric samples, the MannWhitney U test was used and differences between the groups were considered significant at P<0.05.
DISCUSSION The present study did not attempt to compare the effect of FLX with that obtained in a control or placebo group. It was also considered necessary to administer the analgesic drugs iv at the end of anaesthesia to allow sufficient time to obtain an analgesic effect before the animal regained consciousness (Crane 1987). It should be possible to assess the efficacy of any new analgesic drug by comparison with another well established analgesic agent (Casali et al. 1981). Pethidine has been shown to be metabolised rapidly by cats (Booth 1988), to be safe if used with ketamine (Hatch 1973), to be faster and shorter in action (Davis and Donnelly 1968), and more predictable in its effects than other opioid drugs (Waterman
RESULTS The test for normal random variation did not show any differences between the groups. On the clinical tests, analgesia obtained with FLX was similar to that obtained with PDT. In all cases, the maximum level achieved at each time point was 5 1 for the FLX group and 57 for the PDT one. In both groups, mean values were well below the score of 60 points, the point which was defined in this study to indicate insufficient analgesia. Mean pain scores showed that significantly better analgesia was achieved in the PDT group
53
J. vet. Anaesth. Vol. 23(2) (1996)
TABLE 5: Heart and respiratory rates expressed as mean (* sem) in 5 cats at different times after the injection of the analgesic drug (time 0)
Time beatslmin Flunixin Pethidine P breathslmin Flunixin Pethidine P
15
30
45'
60'
75'
190 (k4.5) 137 (k11.6) c0.05
201 (k6.7) 148 (k10.7) c0.05
203 (k7.6) 158 (kl1.6) c0.05
205 (k8.5) 155 (k15.2) <0.05
200 (k7.2) 172 (kl1.2)
189 (k11.2) 176 (k10.7)
NS
NS
32 (k7.6) 23 (k4.9)
42 (k5.8) 28 (k5.4)
57 (k5.8) 43 (k4.5)
NS
53 (k5.4) 34 (k4.0) <0.05
50 (k4.9) 37 (k4.0)
NS
46 (k4.0) 32 (k4.5) c0.05
NS
NS
90
TABLE 6: Blood pressure values expressed as mean (* sem) in 5 cats at different times after the injection of the analgesic drug (time 0)
Time
15
Systolic blood pressure (mmHg) Flunixin mean 109 sern (k14.8) Pethidine mean 86 sern (k4.9) P NS Mean arterial blood pressure (mmHg) Flunixin mean 91 sern (k10.3) Pethidine mean 70 sem (k4.0) P NS Diastolic blood pressure (mmHg) Flunixin mean 64 sern (k7.2) Pethidine mean 53 sem (k2.7) P NS
30'
45
60'
75'
90
1 04 (k13.0)
112 (k8.5)
120 (k7.6)
110 (k7.6)
99 (k7.2)
90 (k4.5)
98 (k5.8)
100 (k4.9)
108 (4.5)
116 (k10.7)
NS
NS
NS
NS
NS
82 (k9.4)
90 (k7.6)
98 (k7.6)
88 (k6.2)
75 (k4.9)
72 (k4.0)
75 (k2.2)
82 (k3.1)
84 (k4.0)
87 (k7.2)
NS
NS
NS
NS
NS
61 (k7.2)
67 (k4.0)
74 (k7.6)
70 (k7.2)
63 (*5.9)
53 (kl.8)
56 (k1.3) c0.05
61 (k4.5)
63 (k2.7)
65 (k5.4)
NS
NS
NS
NS
effects of the inhalation agent and none from the analgesic itself. PDT, in contrast, is likely itself to have caused some sedation. Furthermore, the deeper sedation obtained in cats injected with PDT is partially confirmed by arterial blood pressure values which, although recorded in a small number of cases, were within normal ranges (Haskins 1987). The analgesic effect of FLX in the cat appears to be similar to that reported in the dog (Reid and Nolan 1991; Fonda and Coates 1994). The most important advantage appears to be that, when severe pain is difficult to control, FLX can be used with an opioid drug, taking advantage of the opioid-sparing effect of the NSAIDs (Dahl and Kehlet 1991). There is only one report of FLX toxicity in feline species (Wolf et al. 1991) although, as in the dog, FLX should not be given to any patient at potential risk of renal ischaemia (Smithermann 1992). Other contraindications to the use of FLX in the dog have also been reported, namely interactions
1989). On the basis of studies in the dog, the absorption of pethidine appears to be less erratic after iv injection compared with subcutaneous or even im injection in surgical patients (Kalthum and Waterman 1988). FLX appeared to provide good initial post operative analgesia in the cat without undesirable clinical side effects. Even though most of the surgical procedures undertaken in this series cannot be considered to be very painful (Crane 1987), no cases of vocalisation, prolonged recovery or clinically adverse effects were seen. This lack of overt behavioural evidence of pain during recovery after FLX must be qualified, because differences in the pain and distress behaviour of dogs and cats are now recognised and cats in pain seem less likely to vocalise than dogs (Hansen and Hardie 1993). The lesser sedation observed in patients treated with FLX is consistent with a gradual disappearance of the sedative 54
J. vet. Anaesth. Vol. 23(2) (1996)
London, Bailliere Tindall, p 324. Hansen, B. and Hardie, E. (1993) Prescription and use of analgesics in dogs and cats in a veterinary teaching hospital: 258 cases (1983-1989) J. Am. vet. med. Ass. 202, 1485-1494. Haskins, S.C. (1987) Monitoring of anesthetized patient. In: Principles and Practice of Veterinary Anesthesia Ed: C. E. Short, Baltimore Williams and Wilkins, p 455. Hatch, R.C. (1973) Effects of ketamine used in conjunction with meperidine or morphine in cats. J. Am. vet. med. Ass. 162,964-966. Kalthum W. and Waterman, A. (1988) The pharmacokinetics of intravenous pethidine HCI in dogs: normal and surgical cases. J. vet. Anaesrh. 15,3955. Krohne. S.G. and Vestre, W.A. (1989) Ophthalmic usage of nonsteroidal anti-inflammatory agents. In: Current Veterinary Therapy. Ed: R. W. Kirk, X ed. Philadelphia, Saunders, 642-644. Lees, P. and Taylor, P.M. (1991) Pharmacodynamics and pharmacokinetics of flunixin in the cat. Brit. vet. J. 147,298-305. Lloyd-Thomas, A.R. (1990) Pain management in paediatric patients. Brit. J. Anaesth. 64,85- 104. Mathews, K.A., Doherty, T., Dyson, D.H., Wilcock, B. and Valliant, A. (1990) Nephrotoxicity in dogs associated with methoxyflurane anesthesia and flunixin meglumine analgesia. Canadian vet. J. 31, 766771. McNeil, P.E. (1992) Acute tubulo-interstitial nephritis in a dog after halothane anesthesia and administration of flunixin meglumine and trimetoprim-sulphadiazine. Vet. Rec. 131, 148-151. Reid J. and Nolan, A.M. (1991) A comparison of the post operative analgesia and sedative effects of flunixin and papaveretum in the dog. J. small Anim. Pract. 32,603-608. Rollin, B. (1987) Animal pain, scientific ideology, and the reappropriation of common sense. J. Am. vet. med. Ass. 191, 1222-1226. Smithermann, P. (1992) Intra-operative use of flunixin meglumine. Vet. Rec. 130, 1992. Taylor P.M., Lees, P., Reynoldson, J., Stodulski, G. and Jefferies, R. (1991) Pharmacodynamics and pharmacokinetics of flunixin in the cat: a preliminary study. Vet. Rec. 128, 258. Jefferies, R. and Lees P.(1994) Flunixin in the Taylor, P.M., Winnard J.G., cat: a pharmacodynamic, pharmacokinetic and toxicological study. Brit. vet. J. 150,253-262. Waterman, A.E. (1989) Analgesia in dogs and cats. In: Advances in Small Animal Practice. Ed: E.A. Chandler. Oxford, Blackwell. pp 159-191. Wolf, D.C., Lenz, S.D. and Carlton, W.W. (1991) Renal papillary necrosis in two domestic cats and a tiger. Vet. Pathol. 28,8447. Young, L.E., Brearley, J.C., Richards, D.L.S., Bartram, D.H. and Jones R.S. (1990) Medetomidine as a premedicant in dogs and its reversal by atipamezole. J. small Anim. Pract. 31,554-559.
with gallamine and methoxyflurane (Mathews et al. 1990), with halothane and trimethoprim-sulphadiazine (McNeil 1992), with other steroids (Butterworth and Weaver 1992) or other non-steroidal anti-inflammatory drugs (Elwood et al. 1992).
ACKNOWLEDGEMENTS The author thanks Dr Polly M. Taylor for her encouragement and help.
REFERENCES Bonica, J.J. (1992) Pain research and therapy: history, current status and future goals. In: Animal Pain. Eds: C.E. Short and A. van Poznak, New York, Churchill Livingstone, pp 1-29. Booth, N.H. (1988) Neuroleptanalgesics, narcotic-analgesics, and analgesic antagonists. In: Veterinaty Pharmacology and Therapeutics. Eds: N.H. Booth and L.E. McDonald, VI edn. Ames, Iowa University Press, pp 290-398. Butterworth, S.J. and Weaver B.M.Q. (1992) Drug combination side-effects. Vet. Rec. 129,251-252. Casali, R., Novelli, G.P. and Bonetti, L. (1981) Confront0 tra dipirone e meperidina nel dolore chirurgico. Anestesia e Rianimazione. 22, 143151. Crane, S.W. (1987) Perioperative analgesia: a surgeon's perspective. J. Am. vet. med. Ass. 191, 1254-1257. Cribb, P.H. (1992) Precautions when using anti-prostaglandins. Vet. Clin. N. Am. Small Anim. Pract. 22,370-372. Davis, L.E. and Donnelly, E.J. (1968) Analgesic drugs in the cat. J. Am. vet. med. Ass. 153, 1161-1 167. Dahl, J.B. and Kehlet, H. (1991) Non-steroidal anti-inflammatory drugs: rationale for use in severe post operative pain. Brit J. Anaesrh. 66, 703712. Dodman, N.H. (1992) Advantages and guidelines when using antiprostaglandins. Vet. Clin. N. Am. Small Anim. Pract. 22,367-369. Elwood, C., Boswood, A,, Simpson, K. and Carmichael, S. (1992) Renal failure after flunixin meglumine administration. Vet. Rec. 130,582-583. Fonda, D. (1993) Post operative analgesic effect of flunixin in the cat. J. vet. Anaesth. 20,29. Fonda, D. and Coates, M. (1994) Controllo dell'algia postoperatoria nel cane mediante flunissina. Veterinaria, 8, 1, 23-29. Hall, L.W. and Clarke, K.W. (1991) Veferinaty Anaesthesia. 9th edn.
55
Post operative analgesic actions of flunixin in the cat D. Fonda Clinica Chirurgica Veterinaria, Universita' degli Studi di Milano, Celoria 10, 20133 Milano, Italy
SUMMARY
MATERIALS AND METHODS
The post operative analgesic and sedative effects of flunixin (1 mgkg bwt) iv were investigated for the first 90 min post surgery in 20 cats undergoing a variety of surgical procedures. The results were compared with those obtained in another 20 cats, subjected to similar anaesthetic and surgical procedures, but treated with pethidine, 3 mgkg bwt iv. Post operatively, the analgesic effect of flunixin was shown to be adequate and its administration safe, so that it may reasonably be included among possible post operative analgesic treatments of choice in cats.
All the cats were referred to the Surgical Department of the University of Milan. They were healthy and randomly assigned to the FLX or PDT group. Details of gender, age, weight and duration of anaesthesia are shown in Table 1. The cats were scheduled for a variety of surgical procedures (Table 2). The anaesthetic regimen included premedication with acepromazine (0.25 mgkg bwt) and atropine (0.06 mgkg bwt), given together im, followed after 20 min by ketamine (20 mgkg bwt im) and endotracheal intubation. Anaesthesia was maintained with halothane in oxygen (100%) using a non-rebreathing system (Mapleson C). The cats were given the analgesic drug, flunixin meglumine (1 mgkg bwt iv) or pethidine hydrochloride (3 mg/kg bwt iv), when the halothane was turned o f f . A visual analogue scale (100 mm) was used to measure the pain score post operatively (Reid and Nolan 1991). A score of zero was applied to those animals which were pain free and a score of 100 to those which showed maximum pain. A score of more than 60 points was taken to indicate insufficient analgesia and the need for further analgesic drug. Observations for pain score were carried out for each cat by 3 veterinary students, who were unaware which analgesic drug had been administered. The graphic V.A.S. scale was recorded at 15 min intervals for 1.5 h. Pain assessment involved observation of the response to stimulation of the patient (Lloyd-Thomas 1990). The stimulus was applied either by movement of the treated area or limb in orthopaedic surgery or by finger pressure on the surgical wound. Other clinical changes, including heart and breathing rates, and behavioural alterations which occurred after pain stimulation were recorded. An attempt was made to separate the sedative effect from analgesia. To follow the scoring system previously reported in the dog (Young et al. 1990), evaluation of sedation in the cats was performed on the basis of 9 clinical variables: spontaneous position, placement on side, jaw tone, response to noise, attitude, pedal reflex, palpebral reflex, response to tongue traction, and anal reflex. A sedation score, from a maximum of 34 points in an anaesthetised, sleeping animal, to 0 points in an awake, normal cat, was recorded at the same time intervals. Because of the potential for hypotension at high doses of pethidine, arterial blood pressure was monitored indirectly (Sphygmomanometer Neonatal BP- 107, Nippon Colin) at
INTRODUCTION Advances in the understanding of the pathophysiology of pain (Bonica 1992), together with a renewed awareness of the importance of animal welfare (Rollin 1987), have led to improved post surgical pain control. However, until recently these developments have only been applied in a limited manner to cats. Opiate drugs have had restricted use because of excitement in the case of overdose and of imagined respiratory depression (Hall and Clarke 1991). The older non-steroidal anti-inflammatory agents (NSAIDs) such as phenylbutazone and acetaminophen have not been recommended as analgesics for cats because of toxicity and other untoward effects. Use of the newer NSAIDs, such as meclofenamic acid, naproxen, fenoprofen, ibuprofen, indomethacin, has also been restricted (Dodman 1992). Considerations such as these account for the general failure to provide adequate post operative pain relief in cats. Flunixin (FLX) meglumine is a non-steroidal antiinflammatory drug. It was considered to be toxic in cats by Krohne and Vestre (1989), although no references were given to explain this supposed toxicity (Cribb 1992). In later studies the main pharmacokinetic parameters of FLX were determined in the cat after a single oral or iv administration and no clinical signs of toxicity were seen (Lees and Taylor 1991; Taylor et al. 1991; Taylor et al. 1994). In the present study, the analgesic and sedative effects of flunixine meglumine (1 mgkg bwt iv) were evaluated in 20 cats. Comparison was made with another 20 cats, which underwent similar anaesthetic and surgical procedures, but were given pethidine hydrochloride (PDT), 3 mgkg bwt iv. A preliminary report, with fewer cases and different surgical procedures, has been published (Fonda 1993). 52
J. vet. Anaesth. Vol. 23(2) (1996)
TABLE 3: Pain scores, expressed as mean t sem at different times after the injection of the analgesic drug (time 0)
TABLE 1: Details of the cats included in the study Group 1 (n=20) Flunixin
Group 2 (n=20) Pethidine
10110
1218
Age (mean) range
2y 5m 4m-12y
l y 5m 1.5-4y
bwt (mean) range
3.4 kg 1-7 kg
3 kg 250 g-6 kg
53 min 12-133 min
62 rnin 18-1 20 rnin
Maledfemales
Anaesthesia time (mean) range
Time
Flunixin
Pethidine
15' 30' 45' 60' 75' 90'
7.8 (k2.8) 7.9 (k2.1) 13.3 (k2.9) 15.9 (k2.9) 16.8 (k2.7) 20.8 (k2.6)
1.9 (k0.2) 5.1 (k1.l) 8.9 (kl.8) 12.7 (k2.5) 19.4 (k4.2) 23.3 (k4.9)
P
<0.05 NS NS NS NS NS
TABLE 4: Sedation scores expressed as mean t sem at different times after the injection of the analgesic drug (time 0) Time
TABLE 2: Number of cats undergoing each surgical procedure Surgical procedure Fracture repair Ostectomy Ophthalmic surgery: conjuntival flap keratectomy ocular enucleation third eyelid excision Soft tissue surgery: cleft palate repair npl excision Abdominal surgery: cystotomy ovariectomy
Group 1 Flunixin
Group 2 Pethidine
9
9 2 4
4 (2) (-) (11 (1) 5
(1) (2) (1) 4
(2) (3) 2
15' 30 45 60 75' 90
(-1
29.7 25.4 21.6 19.7 16.4 12.9
(* 0.9) (* 1.4) (* 1.8) (i1.7) (* 1.5) (k 1.5)
Pethidine 31.6 (k 0.7) 28.8 (k 1.1) 24.7 (k 1.4) 23.0 (k 1.3) 20.1 (k 1.3) 16.3 (* 1.1)
P
NS
<0.005 <0.005 <0.005 <0.005 ~0.005
at 15 min with similar pain scores in both groups during,the remaining 75 min (Table 3). In the FLX group, one cat showed pain scores of 50 and 51 after conjunctival flap construction, but it was not considered to need additional, opioid analgesia. In the same group, in spite of low pain scores, 2 cats occasionally attemped to rub their mouths with their paws after cleft palate repair. No other undesiderable responses were observed. FLX treatment produced lower sedation scores than PDT, with statistical significance at all time points after 15 rnin (Table 4). In the 5 cats in which blood pressure was monitored, significant differences were seen in heart and respiratory rates during the first 45 rnin between the 2 drug groups, with higher values in cats injected with flunixin (Table 5). The' difference between the values for systolic, mean and diastolic pressure for the 2 groups did not achieve statistical significance, except at one time point for diastolic pressure (Table 6).
(-1 (1) (3)
1 (2)
Flunixin
(-1 (11
the beginning of this study in 5 cats given pethidine and for comparison in another 5 cats given flunixin. The occlusion cuff was always placed over the medial artery above the carpal joint. Sphygmomanometry allowed the recording of systolic, mean and diastolic pressures and heart rate. Breathing rate was recorded by direct observations over 30 s. Mean (+ sem) values on the scores at each time point were calculated. Variances of the 2 groups were compared using a test for normal random variables (F for P<0.05). A 2tailed 2 samples t-test was used to determine significant differences between the groups. P<0.05 was considered significant. In the comparison of the sedation scores, which were deemed to be non-parametric samples, the MannWhitney U test was used and differences between the groups were considered significant at P<0.05.
DISCUSSION The present study did not attempt to compare the effect of FLX with that obtained in a control or placebo group. It was also considered necessary to administer the analgesic drugs iv at the end of anaesthesia to allow sufficient time to obtain an analgesic effect before the animal regained consciousness (Crane 1987). It should be possible to assess the efficacy of any new analgesic drug by comparison with another well established analgesic agent (Casali et al. 1981). Pethidine has been shown to be metabolised rapidly by cats (Booth 1988), to be safe if used with ketamine (Hatch 1973), to be faster and shorter in action (Davis and Donnelly 1968), and more predictable in its effects than other opioid drugs (Waterman
RESULTS The test for normal random variation did not show any differences between the groups. On the clinical tests, analgesia obtained with FLX was similar to that obtained with PDT. In all cases, the maximum level achieved at each time point was 5 1 for the FLX group and 57 for the PDT one. In both groups, mean values were well below the score of 60 points, the point which was defined in this study to indicate insufficient analgesia. Mean pain scores showed that significantly better analgesia was achieved in the PDT group
53
J. vet. Anaesth. Vol. 23(2) (1996)
TABLE 5: Heart and respiratory rates expressed as mean (* sem) in 5 cats at different times after the injection of the analgesic drug (time 0)
Time beatslmin Flunixin Pethidine P breathslmin Flunixin Pethidine P
15
30
45'
60'
75'
190 (k4.5) 137 (k11.6) c0.05
201 (k6.7) 148 (k10.7) c0.05
203 (k7.6) 158 (kl1.6) c0.05
205 (k8.5) 155 (k15.2) <0.05
200 (k7.2) 172 (kl1.2)
189 (k11.2) 176 (k10.7)
NS
NS
32 (k7.6) 23 (k4.9)
42 (k5.8) 28 (k5.4)
57 (k5.8) 43 (k4.5)
NS
53 (k5.4) 34 (k4.0) <0.05
50 (k4.9) 37 (k4.0)
NS
46 (k4.0) 32 (k4.5) c0.05
NS
NS
90
TABLE 6: Blood pressure values expressed as mean (* sem) in 5 cats at different times after the injection of the analgesic drug (time 0)
Time
15
Systolic blood pressure (mmHg) Flunixin mean 109 sern (k14.8) Pethidine mean 86 sern (k4.9) P NS Mean arterial blood pressure (mmHg) Flunixin mean 91 sern (k10.3) Pethidine mean 70 sem (k4.0) P NS Diastolic blood pressure (mmHg) Flunixin mean 64 sern (k7.2) Pethidine mean 53 sem (k2.7) P NS
30'
45
60'
75'
90
1 04 (k13.0)
112 (k8.5)
120 (k7.6)
110 (k7.6)
99 (k7.2)
90 (k4.5)
98 (k5.8)
100 (k4.9)
108 (4.5)
116 (k10.7)
NS
NS
NS
NS
NS
82 (k9.4)
90 (k7.6)
98 (k7.6)
88 (k6.2)
75 (k4.9)
72 (k4.0)
75 (k2.2)
82 (k3.1)
84 (k4.0)
87 (k7.2)
NS
NS
NS
NS
NS
61 (k7.2)
67 (k4.0)
74 (k7.6)
70 (k7.2)
63 (*5.9)
53 (kl.8)
56 (k1.3) c0.05
61 (k4.5)
63 (k2.7)
65 (k5.4)
NS
NS
NS
NS
effects of the inhalation agent and none from the analgesic itself. PDT, in contrast, is likely itself to have caused some sedation. Furthermore, the deeper sedation obtained in cats injected with PDT is partially confirmed by arterial blood pressure values which, although recorded in a small number of cases, were within normal ranges (Haskins 1987). The analgesic effect of FLX in the cat appears to be similar to that reported in the dog (Reid and Nolan 1991; Fonda and Coates 1994). The most important advantage appears to be that, when severe pain is difficult to control, FLX can be used with an opioid drug, taking advantage of the opioid-sparing effect of the NSAIDs (Dahl and Kehlet 1991). There is only one report of FLX toxicity in feline species (Wolf et al. 1991) although, as in the dog, FLX should not be given to any patient at potential risk of renal ischaemia (Smithermann 1992). Other contraindications to the use of FLX in the dog have also been reported, namely interactions
1989). On the basis of studies in the dog, the absorption of pethidine appears to be less erratic after iv injection compared with subcutaneous or even im injection in surgical patients (Kalthum and Waterman 1988). FLX appeared to provide good initial post operative analgesia in the cat without undesirable clinical side effects. Even though most of the surgical procedures undertaken in this series cannot be considered to be very painful (Crane 1987), no cases of vocalisation, prolonged recovery or clinically adverse effects were seen. This lack of overt behavioural evidence of pain during recovery after FLX must be qualified, because differences in the pain and distress behaviour of dogs and cats are now recognised and cats in pain seem less likely to vocalise than dogs (Hansen and Hardie 1993). The lesser sedation observed in patients treated with FLX is consistent with a gradual disappearance of the sedative 54
J. vet. Anaesth. Vol. 23(2) (1996)
London, Bailliere Tindall, p 324. Hansen, B. and Hardie, E. (1993) Prescription and use of analgesics in dogs and cats in a veterinary teaching hospital: 258 cases (1983-1989) J. Am. vet. med. Ass. 202, 1485-1494. Haskins, S.C. (1987) Monitoring of anesthetized patient. In: Principles and Practice of Veterinary Anesthesia Ed: C. E. Short, Baltimore Williams and Wilkins, p 455. Hatch, R.C. (1973) Effects of ketamine used in conjunction with meperidine or morphine in cats. J. Am. vet. med. Ass. 162,964-966. Kalthum W. and Waterman, A. (1988) The pharmacokinetics of intravenous pethidine HCI in dogs: normal and surgical cases. J. vet. Anaesrh. 15,3955. Krohne. S.G. and Vestre, W.A. (1989) Ophthalmic usage of nonsteroidal anti-inflammatory agents. In: Current Veterinary Therapy. Ed: R. W. Kirk, X ed. Philadelphia, Saunders, 642-644. Lees, P. and Taylor, P.M. (1991) Pharmacodynamics and pharmacokinetics of flunixin in the cat. Brit. vet. J. 147,298-305. Lloyd-Thomas, A.R. (1990) Pain management in paediatric patients. Brit. J. Anaesth. 64,85- 104. Mathews, K.A., Doherty, T., Dyson, D.H., Wilcock, B. and Valliant, A. (1990) Nephrotoxicity in dogs associated with methoxyflurane anesthesia and flunixin meglumine analgesia. Canadian vet. J. 31, 766771. McNeil, P.E. (1992) Acute tubulo-interstitial nephritis in a dog after halothane anesthesia and administration of flunixin meglumine and trimetoprim-sulphadiazine. Vet. Rec. 131, 148-151. Reid J. and Nolan, A.M. (1991) A comparison of the post operative analgesia and sedative effects of flunixin and papaveretum in the dog. J. small Anim. Pract. 32,603-608. Rollin, B. (1987) Animal pain, scientific ideology, and the reappropriation of common sense. J. Am. vet. med. Ass. 191, 1222-1226. Smithermann, P. (1992) Intra-operative use of flunixin meglumine. Vet. Rec. 130, 1992. Taylor P.M., Lees, P., Reynoldson, J., Stodulski, G. and Jefferies, R. (1991) Pharmacodynamics and pharmacokinetics of flunixin in the cat: a preliminary study. Vet. Rec. 128, 258. Jefferies, R. and Lees P.(1994) Flunixin in the Taylor, P.M., Winnard J.G., cat: a pharmacodynamic, pharmacokinetic and toxicological study. Brit. vet. J. 150,253-262. Waterman, A.E. (1989) Analgesia in dogs and cats. In: Advances in Small Animal Practice. Ed: E.A. Chandler. Oxford, Blackwell. pp 159-191. Wolf, D.C., Lenz, S.D. and Carlton, W.W. (1991) Renal papillary necrosis in two domestic cats and a tiger. Vet. Pathol. 28,8447. Young, L.E., Brearley, J.C., Richards, D.L.S., Bartram, D.H. and Jones R.S. (1990) Medetomidine as a premedicant in dogs and its reversal by atipamezole. J. small Anim. Pract. 31,554-559.
with gallamine and methoxyflurane (Mathews et al. 1990), with halothane and trimethoprim-sulphadiazine (McNeil 1992), with other steroids (Butterworth and Weaver 1992) or other non-steroidal anti-inflammatory drugs (Elwood et al. 1992).
ACKNOWLEDGEMENTS The author thanks Dr Polly M. Taylor for her encouragement and help.
REFERENCES Bonica, J.J. (1992) Pain research and therapy: history, current status and future goals. In: Animal Pain. Eds: C.E. Short and A. van Poznak, New York, Churchill Livingstone, pp 1-29. Booth, N.H. (1988) Neuroleptanalgesics, narcotic-analgesics, and analgesic antagonists. In: Veterinaty Pharmacology and Therapeutics. Eds: N.H. Booth and L.E. McDonald, VI edn. Ames, Iowa University Press, pp 290-398. Butterworth, S.J. and Weaver B.M.Q. (1992) Drug combination side-effects. Vet. Rec. 129,251-252. Casali, R., Novelli, G.P. and Bonetti, L. (1981) Confront0 tra dipirone e meperidina nel dolore chirurgico. Anestesia e Rianimazione. 22, 143151. Crane, S.W. (1987) Perioperative analgesia: a surgeon's perspective. J. Am. vet. med. Ass. 191, 1254-1257. Cribb, P.H. (1992) Precautions when using anti-prostaglandins. Vet. Clin. N. Am. Small Anim. Pract. 22,370-372. Davis, L.E. and Donnelly, E.J. (1968) Analgesic drugs in the cat. J. Am. vet. med. Ass. 153, 1161-1 167. Dahl, J.B. and Kehlet, H. (1991) Non-steroidal anti-inflammatory drugs: rationale for use in severe post operative pain. Brit J. Anaesrh. 66, 703712. Dodman, N.H. (1992) Advantages and guidelines when using antiprostaglandins. Vet. Clin. N. Am. Small Anim. Pract. 22,367-369. Elwood, C., Boswood, A,, Simpson, K. and Carmichael, S. (1992) Renal failure after flunixin meglumine administration. Vet. Rec. 130,582-583. Fonda, D. (1993) Post operative analgesic effect of flunixin in the cat. J. vet. Anaesth. 20,29. Fonda, D. and Coates, M. (1994) Controllo dell'algia postoperatoria nel cane mediante flunissina. Veterinaria, 8, 1, 23-29. Hall, L.W. and Clarke, K.W. (1991) Veferinaty Anaesthesia. 9th edn.
55