CONSTANT RATE INFUSION (CRIs) & ANALGESIA Carolyn Cartwright, RVT, VTS (Anesthesia/Analgesia)

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1 CONSTANT RATE INFUSION (CRIs) & ANALGESIA Carolyn Cartwright, RVT, VTS (Anesthesia/Analgesia) Effective approach for optimum pain management requires a practical multimodal anesthesia and analgesia protocol. The goal is to provide the best pain management for the individual patient and achievable for all members of the veterinary team for optimal patient outcomes. We should all strive to be patient advocates, particularly when managing pain. Managing patient pain is part of the Standard of Care, according to the AAHA regulations. The veterinary team needs to be proactive in assessment and application for patient pain management. There are numerous approaches for patient management with a large variety of pain assessment and treatment protocols. Knowledge of the physiology of pain, pharmacology of analgesics and thorough patient evaluation are essential for optimal patient outcomes. Anesthetic allows for surgical, medical or diagnostic procedures for humanitarian reasons. Historically the view was a Triad of anesthesia consisting of narcosis, muscle relaxation and analgesia. Currently, the fourth dimension added is spinal reflex suppression, and is referenced as balanced anesthesia or multimodal anesthesia. Anesthetic drugs have progressed over recent years, although they still fall short of ideal. Consequently, careful preanesthetic assessment of patients before sedation and anesthesia is essential to identify any physiological, pathological or drug-related factors that may complicate anesthetic management. Patient evaluation, special considerations such as proposed procedures, history, breed, drugs, equipment, facility available and the veterinary team member s skill level should be taken into consideration when developing a patient protocol and selecting particular techniques. How do we determine what protocol and when to add analgesics? Patient Management requires - We need to assess if the procedure is: Painful how invasive is the procedure who is performing the procedure and time required is the patient already injured or diseased would the patient benefit from the other effects of analgesics, ex: Sedation - Patient assessment - Providing non-pharmacological comfort and care - Differentiating pain from stress - Appropriate analgesia/sedation - Administering medications and performing analgesic techniques - Monitoring and treating drug effects - Assessing patients pre, intra and post- operatively - Optimal Communication with veterinary team and clients - Maintain Medical record and controlled substance records Recognition and Assessment of the patient pain level is key to optimal pain management - Pain assessment on the awake patient: Pain assessment can be Objective or Subjective data, and can be affected by the assessors skill level and experience - Objective is observation of the autonomic nervous system, endocrine responses and behavior

2 cardiovascular/respiratory response, muscle guarding, movement, food and water intake Objective data is measurable either directly or remotely, by assessing with hands on, telemetry, video or force plate for example. - Subjective Pain Scoring may be affected by the following factors; Temperament Vocalization Posture Locomotion level of sedation behavioral changes There are many pain-scoring systems, from simple to complex. - Simple Descriptive Scale - Visual Analogue Scale - Numerical Rating Scale - Multifactorial Pain Scale Pain assessment on the anesthetized patient requires understanding the responses to nociceptive stimulation under anesthesia. - Generally noxious stimulation causes a stress response - True pain is only experienced by conscious animals - Stress triggers the sympathetic nervous system resulting in increased blood pressure, heart rate, muscle tone and respiratory rate and decreased depth of anesthesia resulting in awakening Understanding animal behavior assists in evaluation

3 Pain Score Systems

4 Categorized Numerical Rating Scales and VAS many available scales are this type Glasgow pain scale validated (used at WCVM) Categories with own numerical scales or VAS 10 cm line Individual behaviors given score Vocalization, muscle guarding etc. Mental attitude Some questions can be directed to owner How willing is your pet to play? How difficult for your dog to lie down? Glasgow Composite Measure Pain Scale: CMPS - Feline Guidance for use The Glasgow Feline Composite Measure Pain Scale (CMPS-Feline), which can be applied quickly and reliably in a clinical setting, has been designed as a clinical decision making tool for use in cats in acute pain. It includes 28 descriptor options within 7 behavioral categories. Within each category, the descriptors are ranked numerically according to their associated pain severity and the person carrying out the assessment chooses the descriptor within each category which best fits the cat's behavior/condition. It is important to carry out the assessment procedure as described on the questionnaire, following the protocol closely. The pain score is the sum of the rank scores. The maximum score for the 7 categories is 20. The total CMPS-Feline score has been shown to be a useful indicator of analgesic requirement and the recommended analgesic intervention level is 5/20. Glasgow Feline Composite Measure Pain Scale: CMPS - Feline Choose the most appropriate expression from each section and total the scores to calculate the pain score for the cat. If more than one expression applies choose the higher score LOOK AT THE CAT IN ITS CAGE: Is it? Question 1 Silent / purring / meowing 0 Crying/growling / groaning 1 Question 2 Relaxed 0 Licking lips 1 Restless/cowering at back of cage 2 Tense/crouched 3 Rigid/hunched 4 Question 3 Ignoring any wound or painful area 0 Attention to wound 1

5 Question 4 a) Look at the following caricatures. Circle the drawing which best depicts the cat s ear position? b) Look at the shape of the muzzle in the following caricatures. Circle the drawing which appears most like that of the cat? APPROACH THE CAGE, CALL THE CAT BY NAME & STROKE ALONG ITS BACK FROM HEAD TO TAIL Question 5 Does it? Respond to stroking 0 Is it? Unresponsive 1 Aggressive 2 IF IT HAS A WOUND OR PAINFUL AREA, APPLY GENTLE PRESSURE 5 CM AROUND THE SITE. IN THE ABSENCE OF ANY PAINFUL AREA APPLY SIMILAR PRESSURE AROUND THE HIND LEG ABOVE THE KNEE Question 6 Does it? Do nothing 0 Swish tail/flatten ears 1 Cry/hiss 2 Growl 3 Bite/lash out 4 Question 7 General impression Is the cat? Happy and content 0 Disinterested/quiet 1 Anxious/fearful 2 Dull 3 Depressed/grumpy 4 Pain Score /20 Universities of Glasgow & Edinburgh Napier Licensed to NewMetrica Ltd. Permission granted to reproduce for personal and educational use only. To request any other permissions please contact jacky.reid@newmetrica.c

6 SHORT FORM OF THE GLASGOW COMPOSITE PAIN SCALE Dog s name Hospital Number Date / / Time Surgery Yes/No (delete as appropriate) Procedure or Condition In the sections below please circle the appropriate score in each list and sum these to give the total score. A. Look at dog in Kennel Is the dog? (i) (ii) Quiet 0 Crying or whimpering 1 Groaning 2 Screaming 3 Ignoring any wound or painful area 0 Looking at wound or painful area 1 Licking wound or painful area 2 Rubbing wound or painful area 3 Chewing wound or painful area 4 In the case of spinal, pelvic or multiple limb fractures, or where assistance is required to aid locomotion do not carry out section B and proceed to C Please tick if this is the case then proceed to C. B. Put lead on dog and lead out of the kennel. When the dog rises/walks is it? (iii) Normal 0 Lame 1 Slow or reluctant 2 Stiff 3 It refuses to move 4

7 C. If it has a wound or painful area including abdomen, apply gentle pressure 2 inches round the site. Does it? (iv) Do nothing 0 Look round 1 Flinch 2 Growl or guard area 3 Snap 4 Cry 5 D. Overall Is the dog? (v) Happy and content or happy and bouncy 0 Quiet 1 Indifferent or non-responsive to surroundings 2 Nervous or anxious or fearful 3 Depressed or non-responsive to stimulation 4 Is the dog? (vi) Comfortable 0 Unsettled 1 Restless 2 Hunched or tense 3 Rigid 4 Total Score (i+ii+iii+iv+v+vi) =

8 Some examples of drugs used to achieve balanced anesthesia are: 2. Analgesia - Opiods can be used for premedication, added intra-operatively and for postoperative pain management - NSAIDS can be used pre or postoperatively ( caution with preoperative administration due to low perfusion if hypotension occurs) - Local anesthetics For protocols on the patient awake, sedated or under general anesthesia, and in combination with other anesthetic techniques. Can be added intra or post-operatively. 3. Narcosis - Isoflurane - Thiopental - propofol 4. Muscle relaxation and reflex suppression - Isoflurane - Thiopental Mu-Opiods in Dogs and Cats Hydromorphone and morphine o o o o o Good sedation Good analgesic for invasive surgery Inexpensive Vomiting possible in dogs Lasts 1-2 hours in the dog; 3-4 hours in cat Meperidine (weak m agonist) o o o Mild sedation Lasts ~1 hour in cats and dogs Never IV (histamine release) Methadone not available in Canada Mu- Opioids for infusions in Dog reduce Isoflurane by about 50% Fentanyl, remifentanil, sufentanil - Powerful opioids for invasive surgery - Fentanyl and sufentanil last minutes -Often used as an infusion with little accumulation over time - Remifentanil broken down in plasma - Only used as an infusion with no accumulation over time - Fentanyl used in awake dogs and cats for analgesia - Bolus: 2-4 g/kg / 6-40 g/kg/hr - Remifentanil (6-40 g/kg/hr) - Use fentanyl for loading bolus

9 - Sufentanil (Bolus: 1-2 g/kg / 2-6 g/kg/hr) -Powerful, short acting may need to ventilate lungs Mu-Opioid Infusions in cats reduce isoflurane by about 15-20% - Cats can have opioid induced excitement - Cats may not metabolize drug as fast as dogs - Not many studies performed in cats Fentanyl (6 g/kg/hr) Sufentanil (0.6 g/kg/hr) Remifentanil (6 20 g/kg/min) Other Opioids in dogs and cats commonly used are butorphanol and buprenorphine, but not used as CRIs. Transdermal Fentanyl Patches - Time to peak plasma concentration hrs in dog 6-12 hrs in cat - Avoid placing patch/skin on heating pad Increases absorption rate - May require additional analgesia - Decreases isoflurane requirements by 18% in cats - Do not use with butorphanol - Placement after surgery - Must have analgesic plan for intermediate period - Patch adhesive contains fentanyl to give bolus - NEVER cut patch - 4 mg/kg/hr size patch recommended for dogs - 25, 50, 75, 100 mg/hr release sizes - 25 mg/hr patch for cats as small as 2kg - Dermal depot in cats, still have fentanyl in circulation following removal of patch - Drug depot effect not seen in dogs - Concentrations fall as soon as patch removed - Effective for cat spay Ketamine Infusions in dogs and cats - Ketamine is a dissociative anesthetic with analgesic properties - Prevents wind-up in spinal cord - Good for severe chronic pain - During anesthesia, lowers isoflurane 25% in dogs mg/kg / mg/kg/hr - Lower dose postoperatively - Side effects - Ventricular arrhythmias - Hypertension - Dysphoria Lidocaine Infusions in dogs and cats - Possibly more for inflammatory and visceral pain? - Lowers isoflurane requirements by 29% in dogs - Can cause hypotension, reduced cardiac contractility Especially in cats; use very carefully at low doses - Anesthetics decrease metabolism Liver blood flow mg/kg/hr (Dog)

10 - Not recommended for cats - Anesthesia slows elimination in cats - Cardiovascular depression Alpha Agonist Infusions 2 Good for intra-operative stability (sedation/analgesia) Dog - Dexmedetomidine in dog ( mg/kg/hr) - Lowers isoflurane concentration mg/kg/hr lowers isoflurane by 18% - 3 mg/kg/hr lowers isoflurane by 59% - Heart rate decreases and blood pressure increases - Cautiously used in ill dogs under anesthesia Cat - Similar infusion rates tested without isoflurane anesthesia Dexmedetomidine - Good analgesic - Good sedative - Does have side-effects that we must consider Bradycardia Hypertension Decreased myocardial contractility - For patients with good cardiovascular reserve Can we combine analgesics? - Yes, each drug can act at a different place within the body - Creates a more powerful way to control pain or make it more bearable - Be aware of how the drugs interact With each other With anesthetic drugs - Know the pharmacology and side-effects Mixing infusions in dogs and cats - Use mixes wisely Opioids, lidocaine, ketamine, alpha 2 adrenergic agonists - Can use lower rates of each drug - Adding all drugs in one bag fluids Less flexibility, inexpensive - Syringe driver for each drug Flexibility to change rates, expensive, cumbersome - Will profoundly lower isoflurane requirements - Morphine, lidocaine, ketamine mix is popular (MLK) % decrease in isoflurane requirements (dog) - FLK also popular (fentanyl instead of morphine)

11 MLK Infusion Cheat-Sheet used to administer - at 0.1mg/kg/hr, - Lidocaine at 50mg/kg/min, - Ketamine 10mg/kg/min - Choose the rate at which you wish to administer the infusion. - 10ml/kg/hr is recommended where the infusion is the only fluid therapy being given and the infusion should - Be made up in a balanced poly-ionic solution such as Hartmanns solution. Care must be taken increasing - Fluid rate in face of hypotension or blood loss will lead to overdose of the morphine, lidocaine and ketamine. - 1ml/kg/hr is suitable in surgery where other sources of fluid therapy are included and the infusion - Piggybacked onto the fluid therapy administration set. The benefit of this option is that changes in the fluid - Therapy rates will not affect the dose of infusion drugs given to the patient. Discontinue ketamine use at end of surgery or signs of ketamine-induced excitement may be seen. A solution with half the above volume of ketamine can be continued into recovery or the ketamine omitted. * DO NOT use lidocaine premixed with epinephrine. This could cause fatal hypertension or dysrhythmias. * Withdraw this volume of fluid from a 1000ml (1 litre) bag of fluids prior to addition of any drugs. When using 500ml bags withdraw, half the volume indicated. Wound Soaker Catheters - Can provide post-op analgesia for 2-3 days - Pre-place during surgery - Commercial kits available (Mila) - Use lidocaine infusions ( mg/kg/min diluted to 2-5 ml/hr lidocaine) or 8-12 hours

12 Opiods in Horses Morphine in Horses - Side-effects of opioids in horses Excitement behaviors Decreased GIT motility - Use IM route and give not longer than 24 hrs - Respiratory depression? - Not always anesthetic-sparing, may increase requirements - Control excitement with sedatives - Acepromazine and/or alpha agonists 2 - Care with distinguishing between opioid excitement and signs of pain - Used at mg/kg IV/IM for horses in pain; lasts ~ 4 hours - May require use of sedatives in awake horses - Morphine alone may cause cardiovascular stimulation - Intra-articular use - 50 mg/joint - Intra-operative use mg/kg bolus followed by 0.1 mg/kg/hr infusion - Improved recovery - No conclusive evidence produces post-op colic - Higher doses can result in rough recoveries - Running or galloping movements in lateral recumbency - Banging head on floor while trying to achieve sternal - Pacing when up Fentanyl, Remifentanil in anesthetized horses - Better given with alpha agonist infusions 2 Fentanyl - Stormy recoveries possible. - Turn off infusion 20 minutes before recovery - 1 mg/kg (slow) then 1.4 mg/kg/hr Remifentanil mg/kg/hr. - Good recovery Butorphanol in horses - Can still produce excitement - Often used intra-operatively mg/kg IV/IM

13 Alpha 2 Infusion 0.01 mg/kg/hr Infusion may cause fecal impaction - Reasonable visceral analgesia - Analgesia short-lasting and not profound require 0.08 mg/kg IM every 3 hours - Can be injected 2-3 times daily for several days - Analgesia not as consistent as with infusion - Less risk of impaction Adrenergic Agonist Infusions in horses for analgesia - Dexmedetomidine used for invasive procedures with isoflurane (inhalational) 0.25 g/kg / 1 3 g/kg/hr - Increases urine output - Stable anesthesia Fentanyl patches in Large Animal Horses x 100 mg/hr patch - Varied results - Peak levels of clinical effect after 12 hours - Some excitement - Acepromazine or alpha 2 to sedate - May need to add another analgesic - Can supplement with NSAIDs - One 100 mg/hr patch can be used in foals - Peak plasma levels after 14 hours Goats and sheep kg (50 mg/hr patch) - Peak levels 8-18 hours (mean 13 hours) - Variable plasma levels in individuals Llamas mg/hr (3 x 100 mg/hr patches) - Peak levels in 12 hours and lasted 72 hours Pigs - 20kg pigs (50 mg/hr); 300kg pigs (two 100 mg/hr) - Place behind ear or inner thigh Ketamine Infusions in Horses - Provides analgesia - Can be used at very low dose in conscious horse mg/kg/hr - Under GA; does not lower isoflurane requirements mg/kg/hr - Standing 1 mg/kg over minutes mg/kg/hr - Risk of excitement - Control with sedatives (alpha 2 best) Lidocaine Infusion in horses (without epinephrine!) mg/kg over 10 minutes, then 3 mg/kg/hr - Use under GA or standing - Found to be useful for somatic but not visceral analgesia in conscious horses - Stop infusion 30 min before recovery to prevent ataxia - Reduces isoflurane requirements - May promote GIT motility?

14 Recipe for 500 kg horse (~$150/day) 32.5 ml loading dose over 10 minutes 375 mls 2% lidocaine in 5L LRS Give at approximately 1L/hr Drip rate 3 drops/sec (10 drop/ml) Horse Recovery - Stop lidocaine and fentanyl infusions 20 minutes before into recovery box. Stop others just before move horse. - Give NSAIDs if warranted (phenylbutazone/flunixin) - Consider nerve blocks if warranted (e.g. intratesticular lidocaine) - Usually sedate with alpha 2 agonist - Romifidine mg/kg IV - Xylazine 0.2 mg/kg IV - Long term morphine may cause ileus - Post-operative analgesics Methylnaltrexone? Fentanyl Patch? Epidural? Not all CRIs are for pain Infusion Rates of Antidysrhythmics, Inotropes & Vasopressors

15 Before finishing anesthesia - Consider repeat dose opioids Anti-emetic at vomiting centre Low dose triggers chemoreceptor trigger zone Usually don t observe vomiting when post-op opioids are given - Consider keeping patient on infusions - Need to watch for side effects Dysphoria Cardiac arrhythmias After Surgery during Recovery Post-operative period - Choose powerful analgesics for invasive surgery - Use several drugs and techniques wisely - Good multimodal regimes vs polypharmacy - Ensure plasma concentrations are maintained - Monitor for pain (use score sheets) - Adjust analgesic regime as necessary - Gradually wean off powerful drugs as healing occurs - Lower anesthetic agents - Lower intensive monitoring post-op, monitor vitals & pain but not dealing with uncomfortable patient through the night - Quicker recovery time - Greater patient comfort & care - Monitor for pain Use pain assessment charts RVTs very skilled

16 Post-operative Opioids - Repeat opioids as necessary - Change infusion rates as necessary - Review analgesic approach - Ice packs - Good nursing care - Use potent opioids for first hours IV if catheter - Hydromorphone (periodic dosing or infusion) - Morphine (periodic dosing or infusion) - Fentanyl (usually infusion) - Remifentanil not reliable in the postoperative setting - Watch for dysphoria, respiratory depression, post-op ileus, urinary retention - Use lower doses if observed, or switch - Consider placing fentanyl patch at this point - When able to move onto less powerful opioids Tramadol (oral efficacy?) Buprenorphine (not with fentanyl patch?) Butorphanol (not with fentanyl patch) Meperidine (short-acting Injectable NSAIDS - Choose drugs licensed for peri-operative use Meloxicam SQ Not recommended for cats pre-anesthetic - Carprofen SQ No reports renal damage in healthy patients No interference with coagulation Keep patient on fluid therapy during anesthesia Mild analgesic Good in combination with other analgesics - Robenocoxib SQ ( Onsior Injectable ) Similar efficacy to meloxicam, shown to be better than buprenorphine for cat spays Benefits to using CRIs - Lower anesthetic agents - Lower intensive monitoring post-op, monitor vitals & pain but not dealing with uncomfortable patient through the night - Quicker recovery time - Greater patient comfort & care Summary - Choose powerful analgesics for invasive surgery - Use several drugs and techniques wisely - Good multimodal regimes vs polypharmacy - Ensure plasma concentrations are maintained - Monitor for pain (use score sheets) - Adjust analgesic regime as necessary - Gradually wean off powerful drugs as healing occurs

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