Do opioids provide adequate analgesia for surgical coeliotomy in teleost fish?

Imagine this clinical scenario...

You are contacted by an ornamental fish keeper who has noticed one of their teleost fish has a distended abdomen. Upon examination, you are suspicious of an abdominal tumour. You plan to perform a coeliotomy under general anaesthesia to identify the cause of the abdominal distention and want to construct an analgesic plan to go with it. You identify opioid analgesia as one potential option, so you decide to consult the evidence to inform whether opioids would be an appropriate choice of perioperative analgesia in this case.

The evidence

Four relevant laboratory-based randomised controlled trials were identified, all of which studied the effects of opioids on teleost fish undergoing surgery under anaesthesia.

Baker et al. (2013) studied 90 adult koi fish obtained from a commercial supplier, 23 male, 19 female, and 48 of unrecorded sex. The fish were split into three groups; treatment only (18/90), treatment with anaesthesia and surgery (36/90), and treatment with anaesthesia but without surgery (36/90). The surgery groups were treated with coeliectomy and unilateral gonadectomy, and the anaesthesia groups were given opioids, one given butorphanol and the other given morphine. The non-anaesthesia group was injected with saline. The outcomes studied were; respiratory rate, food consumption, activity level, interactive level, and hiding behaviour.

Crivelaro et al. (2019) studied 16 male adult Nile tilapia fish, split into a treatment group and control group. The treatment group were given injections of 30mg/kg methadone, while the control group were given the equivalent volume of saline. All of the fish underwent a laparoscopic ventricular partial resection through coelomic access. The outcomes studied were; recovery time, opercular beat rate, caudal fin beat rate, use of cover, and food consumption. The fish were recorded on video post-surgery for analysis.

Gräns et al. (2014) studied 36 rainbow trout obtained from a hatchery, which were evenly distributed into four groups (9 per group); anaesthesia with no surgery or treatment, anaesthesia with treatment but no surgery, anaesthesia with surgery but no treatment, and anaesthesia with surgery and treatment. The fish were then objectively assessed and cardioventilatory data was monitored for 7 days postoperatively.

Harms et al. (2005) studied 30 koi carp obtained from a commercial producer, 20 male, 8 female, and 2 of unknown sex. The fish were split into two treatment groups and a control group, with one treatment group receiving butorphanol, the other receiving ketoprofen, and the control group receiving the equivalent volume of saline. Outcomes studied included; objective assessment, vertical position in water column, activity level, respiratory rate, response to food, and clinical pathology.

Limitations of the evidence

The overall strength of evidence is moderate, partly due to robust study design; all four were randomised controlled trials, and three of them were blinded (Baker et al, 2013, Crivelaro et al, 2019, Harms et al, 2005). However, some limitations in the ways these studies were carried out prevented them from providing strong evidence.

All four studies used randomisation but none of them provided a method of randomisation, so it is unclear whether or not the authors minimised confounding factors. All four also failed to mention the time of year the studies were conducted and the weather temperature, both of which could have influcenced outcomes.

Additionally, there are no species-specific guidelines outlining reliable indicators of pain for teleost fish which may have decreased the accuracy of pain assessments carried out by all four studies. Further research on behavioural indication of pain in teleost fish is required so that outcome selection can be standardised in future studies.

In all four studies, many of the outcomes such as activity level and respiration rate may have been affected by the sedative effect of opioids, which makes it difficult to discern whether outcomes were affected by a reduction in pain, or by adverse effects of the opioids.

Two papers (Baker et al, 2013, Gräns et al, 2014) provided some data in graphical – rather than numerical – format. This makes it difficult for the reader to discern the magnitude of the impact of treatment.

Each of the papers also had unique limitations. Baker et al. (2013) had a single person acting as surgeon and observer with no mention of whether they were blinded to which group each fish was placed in. If they were not blinded, this could have led to bias.

Crivelaro et al. (2019) was limited by its small sample size and an assumption that caudal fin beat rate is representative of all activity levels. Gräns et al. (2014) failed to provide the control group with an equivalent dose of saline, making blinding impossible. Harms et al. (2005) obtained haematology and biochemistry results by comparing pre- and post-surgical values, not by considering normal species reference ranges.

Summary of findings

The findings suggest that perioperative use of opioids for teleost fish undergoing surgery may reduce behavioural changes associated with pain when compared to fish that aren’t given analgesia. However, there is insufficient evidence to determine whether they provide adequate pain relief, and all of the findings must be considered in line with the limitations outlined above.

Baker et al. (2013) found a significant decrease in respiratory rate for all treatment groups compared to the baseline, and no significant differences in hiding behaviour, water column location, and interactive behaviour between the groups. Feeding behaviour in groups that were given an injection of either butorphanol or saline were unchanged. Meanwhile, the surgery group that was treated with analgesia saw a decrease in feeding behaviour, but this was brief compared to the decrease in feeding behaviour displayed by the group that was operated on without analgesia.

Crivalero et al. (2019) found that the mean recovery time was significantly higher in the methadone group than the control group. This was the only statistically significant finding, with the rest of the findings not statistically significant. Ventilation rate was higher in the control group than the methadone-treated group at all time points, swimming activity was higher in the control than methadone group, and no significant difference was seen between groups in food consumption.

Gräns et al. (2014) found that buprenorphine significantly decreased heart rate and ventilation rate when compared with the control group throughout the study, and that surgical intervention did not significantly impact ventilation rate or heart rate in the buprenorphine treated groups.

Harms et al. (2005) found that the butorphanol treated group was the only one not to have significant decreases in caudal fin beat rate and vertical column position. The only clinical difference between treatment groups was a lower increase in creatinine kinase in the ketoprofen group compared with the butorphanol group of the control group. All groups saw a decrease in respiratory rate and a decrease in food consumption post-surgery, but there was no significant difference between them.

Conclusion

The findings suggest that perioperative use of opioids for teleost fish undergoing surgery may reduce behavioural changes associated with pain when compared to fish that aren’t given analgesia. However, there is insufficient evidence to determine whether they provide adequate pain relief, and all of the findings must be considered in line with the limitations outlined above.

Further research is required to measure opioid efficacy and the appropriate doses required to provide surgical analgesia, as well as research into pain indicators in teleost fish.

Disclaimer

The application of evidence into practice should take into account multiple factors, not limited to: individual clinical expertise; patient’s circumstances and owner’s values; country, location or clinic where you work; the individual case in front of you; and the availability of therapies and resources.