Pense-bête

ANALGESIC CONSTANT RATE INFUSIONS
Dr. Robert Stein, Dr. David Thompson, & the VIN Gang


A constant rate infusion (CRI) of analgesic drugs is a simple and effective means of improving patient comfort. Various formulations can be used as a constant rate infusion; the protocol chosen depends on the patient and the degree of pain experienced or anticipated. Some of the commonly used drugs include the following:

1) KETAMINE -- NMDA (N-methyl-D-aspartate) receptors are present in the dorsal horn of the spinal cord and certain areas within the brain. Intense and/or chronic noxious input to the dorsal horn cells (mediated principally by C-fibers) results in the removal of magnesium from the NMDA receptors and their activation by glutamate. This causes prolonged depolarization of spinal neurons (an increase in the magnitude and duration of neuron firing), which leads to an “amplification” of the pain response. This is a significant part of the process of central sensitization (an increase in the excitability of spinal neurons) and may result in hyperalgesia (an excessive response to a painful stimulus) and allodynia ( a painful response to a normally non-painful stimulus).

It is readily apparent that blocking (antagonizing) the NMDA receptors will help to minimize excessively painful responses. Additionally, studies suggest that antagonizing these receptors improves opioid receptor sensitivity, reduces opioid tolerance and minimizes the development of rebound hyperalgesia (the phenomenon of markedly increased pain when opioids are withdrawn).

Ketamine is the most commonly used antagonist of NMDA receptors in veterinary medicine. While its effects as a dissociative anesthetic at standard doses are well known, a new realm of activity occurs when it is delivered at sub-anesthetic doses. At constant rate infusion doses, ketamine blocks receptor activity without causing any dissociative or other adverse effects.

It should be noted that a microdose ketamine CRI should not be used as a sole means of analgesia. It is intended to augment other pain relievers, and should always be used in conjunction with opioids or other analgesics.

2) MORPHINE -- When combined with ketamine in a constant rate infusion, significant analgesia is achieved. The steady-state levels of morphine help to avoid some of the “peak and valley” effects seen with prn administration of opioids. Additionally, its use intraoperatively (as a “piggyback” onto anesthetic maintenance fluids) serves to reduce the amount of anesthetic gas required, which can be useful in decreasing the risk of hypotension.

It can be used in cats at the low end of the dosing spectrum (higher rates may induce significant dysphoria and excitation).

While other opiods can be substituted for morphine, we have elected to only include information for one other mu agonist, fentanyl, in the dosing information section. This reference is not intended to be an exhaustive review of all CRI options but to serve as a solid but basic reference for those adding CRI analgesia to their practice.

3) LIDOCAINE -- The addition of lidocaine has several benefits. For intractable/very severe pain, it adds to the analgesia and sedation. Lidocaine is reported to have some cytoprotective effects, such as weak calcium channel inhibition (which may be helpful in preventing reperfusion injury), and reduced neutrophil chemotaxis and platelet aggregation (which could help significantly in cases with the potential for DIC or SIRS, including GDV’s and splenectomies). Also, lidocaine has some activity in preventing ileus (potentially useful for enterotomies).

Various dosage rates of lidocaine have been advocated. In dogs, rates as low as 10 ug/kg/minute (0.6 mg/kg/hour) provide analgesia, though it may take up to 50 ug/kg/minute (3 mg/kg/hour) for the full cytoprotective and anti-ileus effects. Until further data is available, lidocaine’s use in cats cannot be recommended, due to the potential for toxicity, usually manifested as seizures and severe bradycardia.

CRI DOSING INFORMATION


KETAMINE (100 mg/ml) - 2 to 20 ug/kg/minute (0.12 to 1.2 mg/kg/hr).

    MORPHINE (15 mg/ml) - 2 to 6 ug/kg/minute (0.12 to 0.36 mg/kg/hr).
      LIDOCAINE (20 mg/ml) - 10 to 50 ug/kg/minute (0.6 to 3.0 mg/kg/hr).

        GENERAL INFORMATION



          EXAMPLE FELINE OR CANINE KETAMINE RECIPE

          This simple recipe is based on routine supportive fluid rates of 10 to 20 ml/kg/hr.
          This is the recommended starting recipe for those new to CRI analgesics.
          The following recipe can be used in dogs and cats.

          KETAMINE: Add 60 mg ketamine (0.6 ml) to 1000 ml fluids


            GENERAL INFORMATION



              EXAMPLE FELINE OR CANINE MK RECIPE

              This simple recipe is based on a 1 ml of the final dilution/kg/hr fluid rate.
              The following recipe can be used in dogs and cats.

              KETAMINE: 60 mg/500 ml = 0.6 ml/500 ml diluent = 1.2 ml/1000 ml diluent

                  MORPHINE: 60 mg/500 ml = 4 ml/500ml = 8 ml/1000 ml

                      GENERAL INFORMATION



                                  EXAMPLE CANINE MLK RECIPE

                                  This simple recipe is based on a 1 ml of the final dilution/kg/hr fluid rate.
                                  The following three drugs can be used in any combination for dogs.

                                  KETAMINE: 60 mg/500 ml = 0.6 ml/500 ml diluent = 1.2 ml/1000 ml diluent

                                      MORPHINE: 60 mg/500 ml = 4 ml/500ml diluent = 8 ml/1000 ml diluent
                                          LIDOCAINE: 500 mg/500 ml = 25 ml/500 ml diluent = 50 ml/1000 ml diluent

                                              GENERAL INFORMATION

                                                            ADDITIONAL CRI DRUGS AND DOSES


                                                            FENTANYL – 0.02 to 0.06 ug/kg/minute (0.0012 to 0.0036 mg/kg/hr).