Constant rate infusions (Proceedings)

Traditionally, analgesic drugs like opioids, alpha-2 agents, local anesthetics, NSAIDs and dissociative anesthetics have been administered as a single dose treatment.  When drugs are given in this manner, the patient will experience “peaks” and “troughs” in the plasma drug level.  Administration of drugs via a constant rate infusion will smooth out these high and low levels, enabling the veterinarian to provide a more consistent level of pain control.  Various drugs can be used to prevent pain associated with surgery (preemptive analgesia), reduce the amount of inhaled anesthetic used (improving cardiovascular stability) and control postoperative pain.  Drugs may be utilized in constant rate infusions (CRIs) as a single agent infusion or in combinations to provide multimodal analgesia.  Our goal today is to discuss some of the more popular combinations and how they can be adapted and utilized for your anesthetic and/or pain control plan.

When should you consider using a CRI?  They are very helpful when working with patients with a preexisting problem that now requires surgery, such as fractures, herniated discs, abdominal exploratory, thoracotomies, etc.  They are especially helpful with severe or pathologic pain situations.  Most are administered in an isotonic solution such as LRS or normal saline.  Most drugs are given first as a loading dose and then the infusion started.  They can be given during surgery or after surgery.

Drugs

Opioids

Several different opioids have been used in infusions, including morphine, fentanyl, and hydromorphone.  Opioids produce clinical effects of analgesia, sedation, bradycardia, respiratory depression and vomiting.  They are extremely useful for anesthetized patients as they provide analgesia without cardiovascular depression.  They also have a “MAC” sparing effect:  in other words, their use enables the anesthetist to use less inhaled general anesthetic which also promotes cardiovascular stability.  Patients that exhibit bradycardia (HR<60 bpm) or respiratory depression may need to have the CRI adjusted downward.  Vomiting is unlikely to occur in a painful animal.

Morphine is a full mu (μ) agonist with a duration in the dog of approximately 2-4 hours after a single dose.  It is administered at a rate of 2-6 μg/kg/min when used in an infusion (loading dose 0.5 mg/kg IM if no other full mu agonists have been given).  It can be combined with lidocaine, or ketamine.  Morphine does release histamine, so lowered blood pressure can be seen when high doses are administered rapidly IV.  Cats are prone to dysphoric reactions when administered high doses of morphine.  The drug is light sensitive, so the bag should be covered if considering long term use.

Fentanyl is also a full mu agonist with a short duration of action (30 minutes).  It does not release histamine.  It is most commonly administered as an infusion or via transdermal patch.  It also can be used alone or in combination with other drugs.  The rates vary widely; surgical analgesia can be achieved with CRI rates of 10 to 45 μg/kg/hr and postoperative analgesia with 2-5 μg/kg/hr in dogs and 1-4 μg/kg/hr in cats.  Alternatively, when I don't have a syringe or infusion pump, I take 10 mls of fentanyl (0.050 mg/ml) and add it to a 500 ml bag.  Using a micro drip set that delivers 60 drops/ml, I start at about 1 drop/sec in a medium/large dog (≈ 20-25 kg) and adjust the rate up or down according to blood pressure, heart rate, vaporizer setting, respiratory rate, etc.  Smaller dogs may take a lower rate, but often do well with the same rate.  Fentanyl can be used in cats: loading dose of 5 μg/kg and a CRI rate of up to 24 μg/kg/hr can be used.  High levels of fentanyl should be discontinued 30-45 minutes before the end of anesthesia and a lower rate used for postoperative relief to avoid dysphoria.  Despite its short duration, there can be a lot of individual variation in recovery times for fentanyl infusions.

Hydromorphone can be utilized in CRI as well and may be a good alternative to morphine in cats.  We suggest a loading dose of 0.05 mg/kg IV and a CRI of 0.4 μg/kg/min (24 μg/kg/hr) for postoperative pain or perioperative management.

Lidocaine: 

Lidocaine has been used frequently in the last few years as an aid for patients with neuropathic or other severe pain problems.  A loading dose of 1-2 mg/kg IV is used in the dog, followed by a CRI of 0.6 to 3 mg/kg/hr (10-50 μg/kg/min).  In addition to its analgesic effects, lidocaine has antiarrhythmic effects, promotes GI motility, and reduces the requirement for injectable and inhalant anesthetics.  Potential problems with systemic lidocaine administration include disorientation, twitching, seizures, vomiting, hypotension and cardiovascular depression.  Lidocaine infusions can be used in cats, but caution should be exercised due to the sensitivity and lower threshold to local anesthetic toxicity of the cat.  Lower ends of the range are used in the cats (25 μg/kg/min).  Bupivicaine should not be used intravenously because of its high potential for cardiovascular toxicity.

Ketamine is also helpful for chronic or severe pain problems.  Ketamine (dissociative anesthetic) is an NMDA antagonist in the dorsal horn of the spinal cord.  As such, it helps prevent “windup” and central sensitization of the spinal cord.  A loading dose of 0.5 mg/kg IV is suggested, followed by a CRI of 2-10 μg/kg/min.  The higher rate can be easily accomplished by adding 60 mg of ketamine (0.60 ml) to a liter bag of fluids and deliver at normal anesthesia fluid rates of 10 ml/kg/hr.

Practical Suggestions

• Most of these drugs require a loading dose for maximum efficacy.

• When making infusions with large volumes added, be sure to remove the equivalent volume from the diluent prior to adding the drug:  e.g. remove 50 mls of saline from the bag before adding the lidocaine.

• Protect the bag from ambient light.

Combinations

Morphine and Ketamine (MK)

Combine 60 mg of ketamine and 60 mg of morphine in a 1 liter bag of fluids and deliver at a rate of 2 ml/kg/hr.  This rate can be used for both dogs and cats.  The rate can be adjusted slightly higher for dogs, but care should be taken in cats to watch for dysphoria if a higher rate is used.  Fentanyl can be substituted for morphine by adding 0.6 mg fentanyl (12 mls).  If fluid loading is a concern for your patient, you can add the drugs to a 500 ml bag of fluids and use 1 ml/kg/hr.

Morphine, lidocaine and ketamine (MLK)

Recommendation for dogs

Remove 25 mls from a 1 liter bag of fluids.  Add 25 mls of lidocaine (500 mg).  Add 60 mg ketamine and 60 mg morphine.  Use 2 mls/kg/hr (1 liter bag) or 1 ml/kg/hr if you add the drugs to a 500 ml bag of fluids.

References

Muir WW, Wiese AJ, March PA. Effects of morphine, lidocaine, ketamine, and morphine-lidocaine-ketamine drug combination on minimum alveolar concentration in dogs anesthetized with isoflurane. AJVR 2003; 64; 1155-1160.

Muir WW, Gaynor JS. Handbook of veterinary pain management, St. Louis, 2002, Mosby.