Myoclonus and hypersensitivity of the hind limbs and tail with urinary retention following neuraxial administration of morphine in a cat

An adult female domestic shorthair cat developed myoclonus, muscle rigidity, and hypersensitivity of the hind limbs and tail with urinary retention following neuraxial administration of morphine. Myoclonic contractions resolved following treatment with midazolam and a urinary catheter was placed until normal micturition returned. The cat was clinically normal 36 hours after neuraxial morphine injection. The cat underwent a second surgery without neuraxial morphine and control of postoperative pain required more intervention.Key clinical message:Neuraxial morphine may cause myoclonus and urinary retention. The response to pharmacological treatment of myoclonus is varied, but a benzodiazepine drug may be effective.     

Severe pruritus and myoclonus following intrathecal morphine administration in a dog

During epidural needle placement in a 32-kg dog the subarachnoid space was punctured and half the intended dose of lidocaine, bupivacaine, and morphine was injected. After recovery from anesthesia the dog showed signs of severe pruritus of the tail base and limbs and myoclonus of the tail and hind limbs. Methadone, acepromazine, ketamine, buprenorphine, and butorphanol were administered to control myoclonus and pruritus, but were unsuccessful. Diazepam was used to control myoclonus until the effects of morphine abated.     

Postoperative urinary retention in a dog following morphine with bupivacaine epidural analgesia.

Urinary retention, overflow incontinence, and subsequent detrusor atony were observed following surgery in which a morphine with bupivacaine epidural injection was used for perioperative analgesia. The premise that the urinary retention may have been due to the effects of the morphine component of the epidural is discussed, along with other possible causes.     

Side effects of etomidate in dogs

Intravenous administration of etomidate, a nonbarbiturate sedative hypnotic, induced excitement, myoclonus, pain on injection, vomiting, and apnea during induction of anesthesia in 20 experimental dogs and 70 hospitalized dogs. The dogs had excitement and purposeless muscle movements during recovery from anesthesia. The frequency and severity of the side effects were markedly attenuated or eliminated by the administration of diazepam, acepromazine, or morphine prior to etomidate administration.     

Suspected epidural morphine analgesia induced chronic urinary and bowel dysfunction in a cat

A 12-year-old male castrated domestic shorthair developed chronic urinary retention, constipation and a decreased perineal reflex following a single lumbo-sacral epidural injection of morphine during general anesthesia. Similar adverse effects have been reported in humans following epidural analgesia, but this is the first reported case of both urinary and bowel dysfunction in a cat purportedly from an epidural. The cat was medically managed with manual bladder expressions, intermittent enemas, and various medications including bethanechol, cisapride and stool softeners. The cat continues to have long-term neurologic dysfunction 15 months post-onset. This case report describes a rare but serious potential risk of lumbo-sacral epidural injections in cats.     

Analgesic effects of subarachnoidally administered hyperbaric opioids in horses

OBJECTIVE: To evaluate the effects of subarachnoidally administered hyperbaric morphine, buprenorphine, and methadone on avoidance threshold to noxious electrical stimulation of the perineal, sacral, lumbar, and thoracic regions in horses. ANIMALS: 6 healthy adult horses. PROCEDURES: Horses were assigned to receive subarachnoid administration of hyperbaric morphine (0.01 mg/kg), buprenorphine (0.001 mg/kg), methadone (0.01 mg/kg), or 10% dextrose solution in equal volumes (5 mL). Electrical stimulation was applied every 10 minutes for 60 minutes and every 30 minutes for 120 minutes after subarachnoid injection over the dermatomes of the perineal, sacral, lumbar, and thoracic regions, and the avoidance threshold voltage was recorded. Heart and respiratory rate, blood gas tensions, serum electrolyte concentrations, and sedative effects were also evaluated. RESULTS: Administration of 10% dextrose solution did not change the avoidance threshold. Morphine and methadone significantly increased the avoidance threshold by 10 minutes after injection, which lasted until 120 minutes after subarachnoid administration in the perineal, sacral, lumbar, and thoracic regions. Profound analgesia (avoidance threshold > 40 V) was achieved in all regions. Buprenorphine also significantly increased the avoidance threshold by 10 minutes (36 V) after injection, which lasted 60 minutes and was considered moderate. Heart rate, blood pressure, respiratory rate, and blood gas tensions stayed within reference range. No ataxia, signs of sedation, or CNS excitement were observed. CONCLUSIONS AND CLINICAL RELEVANCE: Subarachnoid administration of hyperbaric morphine or methadone produces intense analgesia for 120 minutes over the dermatomes of the perineal, sacral, lumbar, and thoracic areas without cardiorespiratory depression, ataxia, or CNS excitement in horses.     

Intrathecal morphine overdose in a dog

CASE DESCRIPTION: A healthy 6-year-old 28.5-kg (62.7-lb) spayed female Boxer undergoing surgical repair of a ruptured cranial cruciate ligament was inadvertently administered an overdose of morphine (1.3 mg/kg [0.59 mg/lb]) via subarachnoid injection. CLINICAL FINDINGS: 50 minutes after administration of the overdose, mild multifocal myoclonic contractions became apparent at the level of the tail; the contractions migrated cranially and progressively increased in intensity and frequency during completion of the surgery. TREATMENT AND OUTCOME: The myoclonic contractions were refractory to treatment with midazolam, naloxone, phenobarbital, and pentobarbital; only atracurium (0.1 mg/kg [0.045 mg/lb], IV) was effective in controlling the movements. The dog developed hypertension, dysphoria, hyperthermia, and hypercapnia. The dog remained anesthetized and ventilated mechanically; treatments included continuous rate IV infusions of propofol (1 mg/kg/h [0.45 mg/lb/h]), diazepam (0.25 mg/kg/h [0.11 mg/lb/h]), atracurium (0.1 to 0.3 mg/kg/h [0.045 to 0.14 mg/lb/h]), and naloxone (0.02 mg/kg/h [0.009 mg/lb/h]). Twenty-two hours after the overdose, the myoclonus was no longer present, and the dog was able to ventilate without mechanical assistance. The dog remained sedated until 60 hours after the overdose, at which time its mentation improved, including recognition of caregivers and response to voice commands. No neurologic abnormalities were detectable at discharge (approx 68 hours after the overdose) or at a recheck evaluation 1 week later. CLINICAL RELEVANCE: Although intrathecal administration of an overdose of morphine can be associated with major and potentially fatal complications, it is possible that affected dogs can completely recover with immediate treatment and extensive supportive care.     

Combined spinal-epidural anesthesia in a dog

OBJECTIVE: To report use of combined spinal epidural anesthesia for tail resection and surgical exploration of the pelvic canal and the perineal-pararectal area in a dog. ANIMAL: A 4-month-old, 13 kg male Collie dog. METHODS: Under inhalant anesthesia, an epidural catheter was threaded through a Tuohy needle at L5-L6. Then using a Whitacre spinal needle bupivacaine and fentanyl were administered in the subarachnoid space at L6-L7 level. Fifteen minutes later, morphine was administered epidurally. Bupivacaine and morphine were administered epidurally 4 hours after the subarachnoid injection. RESULTS: No cardiorespiratory response to surgical stimulation was observed. Postoperative analgesia was satisfactory, and the catheter was removed 30 hours later. No complications or neurologic sequelae occurred before discharge or were noted 10 days later. CONCLUSION: Combined spinal-epidural anesthesia provided excellent intraoperative anesthesia and perioperative analgesia in a dog undergoing surgery involving the pelvic canal. CLINICAL RELEVANCE: Combined spinal-epidural anesthesia can be performed in dogs, and its use should be considered in major surgeries caudal to the diaphragm, as the epidural catheter allows cranial extension of the block, providing excellent intraoperative anesthesia and perioperative analgesia.     

Experiences With Morphine Injected Into the Subarachnoid Space in Sheep

The effects of morphine (M), 0.1 mg/kg, administered into the lumbosacral subarachnoid space of sheep used for experimental stifle surgery, were investigated. In a pilot study, preservative-free morphine was administered to three sheep, morphine containing preservatives to two sheep, and saline (S) to one sheep. After recovery from anesthesia, all five sheep administered M displayed rear limb weakness. One sheep, which had received morphine containing preservatives, also licked and chewed incessantly at its flank and hindquarters during recovery. A group of 24 sheep was used to study the effects of morphine containing preservatives, injected intrathecally, on recovery from general anesthesia and hindlimb orthopedic surgery. Eight sheep received M, eight sheep received S, and eight sheep had a needle placed in the subarachnoid space without any injection (N). Times from end of anesthesia to standing varied greatly and did not differ significantly among groups (P=.73), with M sheep averaging 119 minutes; S sheep, 87 minutes; and N sheep, 83 minutes. One sheep administered M licked and chewed at its hindquarters during recovery. Another group of 24 sheep was used to study the effects of morphine containing preservatives, injected intrathecally, on postoperative lameness. Treatments were as described previously. Sheep were videotaped intermittently for 36 hours after surgery, and each sheep was scored as follows; 0 = not lame; 1 = slightly lame; and 2 = very lame. The average lameness scores, which did not differ significantly among groups (P=.21), were: M sheep, 1.07; S sheep, 0.81; and N sheep, 0.68. One sheep administered M displayed extensor spasms of the hindlimbs, and could not stand until several hours after surgery. We conclude that subarachnoid morphine at the dosage used produces no apparent benefit in sheep which have had stifle surgery, and in fact may cause detrimental side effects, such as hindlimb weakness, and pruritis or irritation of the hindquarters.     

INTRACRANIAL SUBARACHNOID HEMORRHAGE FOLLOWING LUMBAR MYELOGRAPHY IN TWO DOGS

Intracranial subarachnoid hemorrhage is a rare but serious complication of lumbar puncture in humans. Possible sequelae include increased intracranial pressure, cerebral vasospasm, or mass effect, which can result in dysfunction or brain herniation. We describe two dogs that developed intracranial subarachnoid hemorrhage following lumbar myelography. In both dogs, myelography was performed by lumbar injection of iohexol (Omnipaque). Both the dogs underwent uneventful ventral decompressive surgery for disk herniation; however, the dogs failed to recover consciousness or spontaneous respiration following anesthesia. Neurologic assessment in both dogs postoperatively suggested loss of brain stem function, and the dogs were euthanized. There was diffuse subarachnoid hemorrhage and leptomeningeal hemorrhage throughout the entire length of the spinal cord, brain stem, and ventrum of brain. No evidence of infectious or inflammatory etiology was identified. The diagnosis for cause of brain death was acute subarachnoid hemorrhage. Our findings suggest that fatal subarachnoid hemorrhage is a potential complication of lumbar myelography in dogs. The cause of subarachnoid hemorrhage is not known, but may be due to traumatic lumbar tap or idiosyncratic response to contrast medium. Subsequent brain death may be a result of mass effect and increased intracranial pressure, cerebral vasospasm, or interaction between subarachnoid hemorrhage and contrast medium.     

Results of preemptive epidural administration of morphine with or without bupivacaine in dogs and cats undergoing surgery: 265 cases (1997-1999)

OBJECTIVE: To determine prevalence of adverse effects associated with epidural administration of morphine with or without bupivacaine in dogs and cats undergoing surgery and evaluate effects of epidural administration of morphine on postoperative pain severity. DESIGN: Retrospective study. ANIMALS: 242 dogs and 23 cats. PROCEDURE: Morphine with or without bupivacaine was administered prior to surgery with a Tuohy needle, spinal needle, or epidural catheter. In 18 dogs that underwent surgery twice, results of preemptive epidural administration of morphine with or without bupivacaine were compared with results of systemic administration of oxymorphone and ketoprofen. RESULTS: The delivered fraction of isoflurane was significantly lower in animals given morphine and bupivacaine than in animals given morphine alone. Analgesia was of significantly longer duration in dogs given morphine and bupivacaine than in dogs given morphine alone. During anesthesia, mild respiratory and cardiovascular depression was reported. Seven dogs and 2 cats had urine retention, and 2 dogs developed pruritus. Six dogs vomited when a second dose of morphine was given epidurally the day after surgery. Eight of 72 dogs had delayed hair growth. In 18 dogs that underwent surgery twice, the delivered fraction of isoflurane was significantly lower and the duration of analgesia was significantly longer when morphine with or without bupivacaine was given epidurally than when oxymorphone and ketoprofen were given. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that preemptive epidural administration of morphine with or without bupivacaine is a safe and effective method of inducing long-lasting analgesia in dogs and cats and is superior to standard management of postoperative pain with repeated injection of oxymorphone and ketoprofen.     

A retrospective study of efficacy and side effects of intrathecal administration of hyperbaric bupivacaine and morphine solution in 39 dogs undergoing hind limb orthopaedic surgery

ObjectiveTo evaluate the intraoperative efficacy of intrathecal anaesthesia with hyperbaric bupivacaine 0.5% and morphine 1% solution (HIA) in dogs undergoing hind limb orthopaedic surgery, using the cardiovascular response to surgical stimulation and to report the perioperative side effects.Study designRetrospective clinical study.AnimalsForty-three dogs that underwent general anaesthesia for hind limb orthopaedic surgery between 2010 and 2011.MethodsThe anaesthesia records of dogs that received HIA were reviewed. The bupivacaine and morphine doses were calculated based on body mass (BM) and spinal cord length (SCL). Cardiovascular response (CR) to surgical stimulation, the incidence of hypotension, bradycardia, urinary retention, pruritus and offset of motor block were all reported. The intraoperative time-to-event probability of CR was analyzed using Kaplan–Meier survival analysis.ResultsThe median (range) bupivacaine dose related to BM was 0.57 (0.40–0.78) mg kg^?1, while that related to SCL was 0.13 (0.08–0.19) mg cm^?1. A CR was observed in 3/39 (8%) dogs within the first hour after intrathecal injection (Ii) and in 9/39 (23%) dogs over the entire duration of surgery. At 70 minutes from Ii the event-free probability of CR fell below 80%. Hypotension was observed in 12/39 (31%), bradycardia in 6/39 (15%), pruritus in 3/39 (8%), and urinary retention in 3/39 (8%) dogs respectively. Five hours after Ii, 35/39 (89%) dogs were able to walk with only residual ataxia.Conclusions and clinical relevanceIntrathecal anaesthesia with hyperbaric bupivacaine 0.5% and morphine 1% solution provided effective intraoperative antinociception up to 70 minutes in dogs undergoing hind limb surgery. The technique of HIA can provide effective analgesia during short hind limb surgeries in dogs.     

The disposition and local effects of intra-articular morphine in normal ponies

Morphine (15 mg in 5 ml saline) was injected into the left, and 5 ml saline into the right, tarsocrural joint of 8 ponies. Venous blood samples were collected before and at 0.5, 1, 2, 6 and 24 h after the intra-articular morphine injection and analysed for morphine and its metabolites. Synovial fluid was sampled from both tarsocrural joints before and 24 h after injection. Synovial white blood cell and red blood cell counts, protein and hyaluronate concentrations were measured in all the samples; and the synovial fluid morphine concentration from the left tarsocrural joint was measured 24 h after the injection. The peak mean plasma morphine concentration (7.1 μg/l) was detected in samples taken 0.5 h after the intra-articular morphine injection, but neither morphine nor its metabolites were found in plasma 6 h or more post injection. Morphine was detected in the synovial fluid of each pony 24 h after the injection. The plasma morphine or morphine-6-glucuronide concentrations were lower than those likely to have any systemic effect. The synovial fluid white blood cell count and protein concentration were increased and hyaluronate concentration decreased in samples taken 24 h after the intra-articular morphine injection, compared to the pre-injection samples. No differences were found between morphine and saline injected joints. It was concluded that morphine did not irritate the joint more than saline.     

The influence of furosemide on plasma elimination and urinary excretion of drugs in standardbred horses

A study of the effects of intravenous administration of either 150 mg or 250 mg of furosemide to standardbred mares pre-treated with other drugs was undertaken to determine whether a unique pattern of drug elimination into urine and from plasma for each compound occurred. Furosemide significantly reduced the plasma concentrations of codeine compared to control 2-6 h after furosemide administration. In contrast, the plasma concentrations of theophylline, phenylbutazone, pentazocine, guaifenesin and flunixin were not markedly altered by furosemide. In the case of acepromazine, clenbuterol and fentanyl, the data generated were insufficient to state with certainty whether or not furosemide affected the plasma concentrations of these three drugs. A significant reduction was noted in the urinary concentrations of guaifenesin, acepromazine, clenbuterol, phenylbutazone, flunixin, fentanyl and pentazocine within 1-4 h of furosemide administration. The urinary concentrations of theophylline remained reduced as long as 8 h after furosemide injection. Furosemide administration to horses pre-treated with codeine resulted in depression of urinary morphine concentrations 2-4 h and 9-12 h after furosemide injection. A lower furosemide dose (150 mg) produced changes in drug urinary excretion and plasma elimination equivalent to the higher dose (250 mg). It is evident that furosemide affects the urinary and plasma concentrations of other co-administered drugs but not in a predictable fashion, which limits the extrapolation of these results to as yet untested drugs.     

Reverse tolerance to the stimulant effects of morphine in horses

Horses were given 4 intravenous injections of morphine sulfate, 0.5 mg per kg, spaced two days apart. The motor response to morphine was measured by counting the number of steps taken with the left foreleg during a 4 minute interval at various times after the injection. By the third injection of morphine there was a significant increase in motor response. This sensitization or reverse tolerance persisted for several weeks after the last injection. Cross-sensitization also developed to the stimulant effects of apomorphine. This finding suggests that sensitization to the stimulant effects of morphine may involve dopamine receptors in the central nervous system.     

Postoperative analgesia in dogs receiving epidural morphine plus medetomidine

This investigation was carried out to compare the postoperative analgesia and plasma morphine concentrations in dogs given epidural morphine or epidural morphine combined with medetomidine prior to surgery. Twelve dogs (seven males and five females) with ruptured cranial cruciate ligaments presented to the Washington State University Veterinary Teaching Hospital. Six dogs received an epidural injection of morphine (0.1 mg/kg) and six dogs received epidural morphine (0.1 mg/kg) combined with medetomidine (0.005 mg/kg). Numeric rating scale (NRS) pain scores and cumulative pain scores (CPS) were assigned to 10-min segments of video. Video segments, heart rates and respiratory rates were recorded prior to premedication and at 4, 8, 12, 18 and 24 h after epidural injection. Blood was sampled from the cephalic vein at each of these times and during anesthesia at 0.5, 1, 2 and 3 h after epidural injection. Data were analyzed using either Friedman's test or one-way anova for repeated measures. In the morphine group, significant increases compared with premedication values were detected at 4, 8 and 12 h after epidural injection for NRS and at 4 and 12 h after epidural injection for CPS. In the morphine plus medetomidine group, NRS was significantly higher at 4 and 8 h whereas there were no differences from baseline values for CPS. Plasma morphine concentrations were not significantly different between treatment groups, but were significantly increased compared with preinjection values at 0.5, 1, 12, 18, and 24 h in the morphine plus medetomidine group. Epidurally administered morphine combined with medetomidine was associated with only minor benefits based on subjective pain scoring when compared with morphine alone in these dogs undergoing repair of a ruptured cranial cruciate ligament.     

Hypobaric intrathecal anaesthesia for partial hemipelvectomy in a dog.

OBJECTIVE : To report the intrathecal use of a hypobaric anaesthetic solution for partial hemipelvectomy in a nine-year-old, neutered female, Golden Retriever dog, weighing 34 kg. METHODS : Under inhalational anaesthesia, with the dog lying in lateral recumbency and the surgical side uppermost, 1.9 ml of a hypobaric solution containing 3.42 mg of bupivacaine and 0.66 mg of morphine were administered in the subarachnoid space at L5-6 level 30 minutes before surgery. Following the intrathecal injection the dog was maintained for five minutes in a 10 degrees head-down position, then for three minutes in a 10 degrees head-up position. RESULTS : Apart from a transient increase in heart and respiratory rates during resection of the sartorius muscle, which was treated with a plasma Target Controlled Infusion (TCI) of fentanyl, spinal anaesthesia provided cardiovascular stability and excellent relaxation of the surgical site. Neither motor blockade nor proprioceptive deficit were apparent in the contra-lateral hind limb at recovery, 200 minutes after injection. Postoperatively, rescue analgesia was not required in the 48 hours following surgery. CLINICAL SIGNIFICANCE : In dogs, the use of intrathecal hypobaric bupivacaine and morphine as a part of a balanced anaesthetic protocol should be considered during unilateral major orthopaedic surgeries of the pelvis and hind limb, as it allowed a reduction in the dose administered compared to isobaric solutions, providing selective spinal anaesthesia, excellent long-lasting analgesia, and rapid recovery of ambulation.     

The post-operative analgesic effects of epidurally administered morphine and transdermal fentanyl patch after ovariohysterectomy in dogs

ObjectiveTo investigate the analgesic and side effects of epidural morphine or a fentanyl patch after ovariohysterectomy in dogs.Study designProspective, randomized clinical study.AnimalsTwenty female mongrel dogs undergoing ovariohysterectomy.MethodsThe dogs were allocated to one of two groups: epidural morphine or transdermal fentanyl patch. Anaesthesia was induced with propofol and maintained with isoflurane. Morphine (0.1 mg kg^?1) was administered epidurally in the epidural morphine group and a transdermal fentanyl patch was applied 24 hours before the operation in the fentanyl patch group.The heart rate, respiratory rate, body temperature, plasma cortisol concentration, and sedation and analgesia scores were recorded during the 24 hour post-operative period. Adverse effects such as vomiting, anorexia, skin reactions, urinary retention, and time to start licking the surgical site were also recorded. p < 0.05 was considered significant. Statistical analyses utilized anova for repeated measures, Friedman tests, Mann-Whitney U-tests and independent sample t-tests as relevant.ResultsPain scores were lower in the epidural group than in the fentanyl group at all post-operative times. The dogs in the epidural morphine group were calm and relaxed, whereas discomfort and vocalization were recorded in the fentanyl patch group. The sedation scores were higher in the fentanyl patch group throughout the 12 hour period. Salivation and anorexia lasted longer in the fentanyl patch group than in the epidural morphine group. Plasma cortisol concentrations were high in the early post-operative period in both groups. The fentanyl patch group had higher cortisol concentrations than the epidural morphine group. Slight erythema was recorded in two dogs when the patches were removed.Conclusion and clinical relevanceEpidurally administered morphine provided better analgesia and caused fewer adverse effects than the fentanyl patch after ovariohysterectomy in dogs.     

Pharmacokinetics and pharmacodynamics of morphine in llamas

OBJECTIVE: To assess the pharmacokinetics and pharmacodynamics of morphine in llamas. ANIMALS: 6 healthy adult llamas. PROCEDURES: Llamas received morphine sulfate in a randomized crossover design. In phase 1, they received IV or IM administration of morphine at 0.05 or 0.5 mg/kg, respectively; in phase 2, they received IV administration of morphine at 0.05, 0.25, or 0.5 mg/kg. Plasma morphine and morphine-6-glucuronide concentrations were determined by validated methods. Body temperature, heart rate, respiratory rate, sedation, and analgesia were assessed and compared with plasma concentrations by regression analysis. RESULTS: Total body clearance was similar between IV administration of morphine sulfate at 0.25 and 0.5 mg/kg (mean +/- SD, 25.3 +/- 6.9 mL/min/kg and 27.3 +/- 5.9 mL/min/kg, respectively), and linearity was demonstrated between these doses. Bioavailability of morphine following IM administration at 0.5 mg/kg was 120 +/- 30%. Body temperature and sedation increased as the dose of morphine administered increased. Heart rate was unaffected by varying doses. Respiratory rate decreased as dose increased. Analgesia was difficult to assess as a result of high individual variability. Intravenous administration of morphine at 0.25 mg/kg provided the most consistent increase in tolerance to electric stimulation. Pharmacodynamic modeling revealed a sigmoidal relationship between plasma concentration and sedation score. CONCLUSIONS AND CLINICAL RELEVANCE: Morphine was characterized by a large apparent volume of distribution and high systemic clearance in llamas. A prolonged half-life was observed with IM injection. Intravenous administration of morphine sulfate at 0.25 mg/kg every 4 hours is suggested for further study.     

Cardiorespiratory effects and efficacy of morphine sulfate in winter flounder (Pseudopleuronectes americanus)

OBJECTIVE: To assess the cardiorespiratory effects of morphine sulfate and evaluate whether morphine blocks cardiac responses to a noxious stimulus in winter flounder. ANIMALS: 42 winter flounder (Pseudopleuronectes americanus) that were acclimated at 10 degrees C. PROCEDURES: Each fish was fitted with a Doppler flow probe around the ventral aorta; cannulae were placed for injection of drug or saline (0.9% NaCl) solution and assessments of respiration. Selected cardiorespiratory variables were measured in morphine-injected (40 mg/kg, IP [n = 18] or 17 mg/kg, IV [2]) or saline solution-injected (1.6 mL [22]) fish at various intervals. Heart rate and cardiac output (CO) were also measured in flounder that were injected with saline solution (n = 19) or morphine (10) and received a noxious or innocuous stimulus (injection of 5% acetic acid or saline solution SC into a cheek) 50 minutes later. RESULTS: Morphine administration promptly induced marked bradycardia (and a concomitant reduction in CO), followed by prolonged (> 48 hours) increases in CO and heart rate. Morphine injection only transiently affected respiratory rate. Application of a noxious stimulus to control flounder resulted in a significant (10%) but transient (< 5 minutes' duration) increase in CO, which was completely blocked by prior administration of morphine. CONCLUSIONS AND CLINICAL RELEVANCE: Although morphine blocked the response to a noxious stimulus in fish, its cardiovascular effects might preclude its use in many research situations. Investigation of the dose dependency of these cardiovascular effects and their interspecific variation is required to determine the applicability of morphine for use in fish.