The nuts and bolts of analgesic infusions for private general practice (Proceedings)

Analgesics administered by intermittent bolus create broad swings in drug plasma levels. Constant rate intravenous infusions (CRIs) are manually controlled titratable infusions. CRIs establish more consistent plasma levels and better overall control of drug effects. Mu agonist opioids, lidocaine, and ketamine are the most frequently utilized analgesics providing an effective multimodal benefit with low potential for adverse events. While delivery is possible through a standard gravity drip set, most prefer the fine control provided by an IV fluid pump or syringe pump. Calculators are available to eliminate the worry associated with drug delivery calculations. Analgesic CRIs not only contribute to compassionate pain relief, they can also help contribute to a balanced anesthetic program, reducing maintenance agent requirements, frequently improving patient blood pressures and ventilation. This session will focus on the details of how you can easily integrate analgesic CRIs into daily practice in the primary care setting.

Overview of presentation

Constant Rate Infusions have become a frequently utilized analgesic delivery method in the primary care setting. Delivering drugs via this route allows for a more consistent drug delivery that avoids the peaks and valleys associated with intermittent administration. CRIs also allow for much greater control of the medications' effects, both positive and negative.

Common Manual Infusion Drugs and Dose Rates

Target controlled infusions (TCIs) are more sophisticated infusion methods requiring computerized delivery systems. TCIs require a detailed understanding of the given drug's species specific pharmacokinetics. You might think of a TCI as a precision vaporizer with a specific drug delivery scale while a CRI is more like a non-precision vaporizer providing more general low, medium, high range guidance. Most importantly, unlike TCIs, CRIs are a practical method for any practice.

Drugs commonly delivered through CRIs include morphine, hydromorphone, fentanyl, ketamine, midazolam, lidocaine, and dexmedetomidine. The opioids provide titratable analgesia that benefits the patient at the peripheral and central levels. Nausea, clinically relevant bradycardia and respiratory depression are not expected at normal analgesic dose rates. Ketamine enhances analgesia via different mechanisms; NMDA antagonism reducing central sensitization, enhancing opioid analgesia, reducing the risk of opioid induced hyperalgesia and opioid tolerance as well as possible direct analgesia via the D2 dopamine receptors. Midazolam provides sedation and relaxation, central analgesia, as well as a MAC sparing effect that can be of major benefit for patients experiencing problematic isoflurane or sevoflurane induced hypotension. Lidocaine is capable of enhancing analgesia while providing anti-inflammatory, reperfusion, cerebral protectant and GI motility benefits. Dexmedetomidine is attractive as an anxiolytic as well as a tool for enhanced patient analgesia.

CRIs are most commonly delivered through the IV fluid bag route or directly using a syringe pump. The IV fluid bag route is attractive because it allows for precise delivery rates using equipment already available at most practices. The simplest method involves a single fluid bag providing both the drug delivery as well as the patient's fluid needs. The downside to this method is the inability to adjust the fluid rate without changing the drug delivery rate. To maximize the flexibility of this method you generally need to pick low to midrange drug dose rates so that adjustments in the patient's fluid need don't take you outside of recommended drug dose rates.

You can expand your flexibility by running separate fluid lines through different IV fluid pumps. In the two-pump model, the CRI drugs would be delivered at a very low rate (ex. 1 ml/kg/hr) while the patient's additional fluid needs are separately managed through the second line. This allows for greater flexibility of drug and fluid delivery but requires multiple pumps and multiport IV access.

The greatest level of flexibility is gained when each analgesic is delivered through its own IV fluid bag. This allows for variable adjustments of each drug independent of the other but requires the greatest equipment resources and IV access ports.

While the calculations of the various CRI delivery options may seem daunting, this headache has been eliminated by easy to use calculators directly available online. These calculators allow you to vary the IV fluid bag size, fluid delivery rate, and drug dose rates to satisfy any conceivable combination.

Although the author does not generally recommend using gravity administration for analgesic CRIs this may be a consideration in some settings. Delivering gravity administered CRIs through a buretrol maximizes control over drug delivery while also setting a limit to the maximum amount of drug delivered.

Syringe pumps are the most ideal way to deliver CRI drugs. The author prefers syringe pumps like the Medfusion 2001 and 2010i which are readily available on the secondary equipment market. The Razel Scientific Company makes very solid volume delivery based syringe pumps that cost $50.00 to $200.00 used and $550.00 to $800.00 new.

When starting to explore CRI use, running a single agent ketamine CRI at 0.4 to 0.6 mg/kg/hr dose rate is a good start point. This should enhance the preanesthetic opioid analgesia without having a dramatic effect on the overall patient appearance or inhalant agent needs. After the staff has developed an initial comfort zone with ketamine only CRIs consider adding lidocaine and morphine at the lower end of their dose rate range (see chart below). Gradually work up to midrange combinations of the three drugs as the staff's comfort zone expands, allowing the staff to see how the inhalant needs of the average patient decline as the CRI drug effects increase. The final step involves upper dose rate deliveries for the more painful procedure. Expect a significant reduction in the patient's inhalant requirements. The staff's comfortable acceptance of analgesic CRIs will be enhanced if you first apply these techniques to young healthy routine surgeries like spays and neuters.

CRIs should be preceded by loading doses. Loading doses are needed in order to achieve initial therapeutic blood levels. Without loading doses, it would take 3 to 5 half-lives of each drug to reach reasonably steady state drug levels. Remember that these loading doses may, indeed, be covered by the patient's preanesthetic or induction medications.

Typically, an analgesic CRI is slowed towards the end of the anesthetic procedure and discontinued just prior to the patient's recovery to facilitate extubation. The CRI is then reinitiated at 25 to 50% of the intraoperative drug dose rates with ongoing adjustments based on patient need. Most clinicians will also adjust the postoperative drug combinations and ratios, often dropping the lidocaine to low end dose rates if not discontinuing it altogether.

The duration of analgesic infusions are not specifically limited with respect to any set number of days. For some extremely painful patients the CRI may be continued over several days. It is a clinician's judgment as to the relative day to day dose rate reductions that should be effected as tissue stores become saturated by the medications. It should be no surprise that higher dose, longer duration infusions will lead to a more sustained patient effect after discontinuation of the infusion. While the stability of morphine-ketamine saline solutions has been demonstrated out to 4 days, it is not clear how stable other drug combinations in fluid types other than saline would be. When morphine CRI solutions are used for longer than a few hours it is recommended that the bag be covered with a light-proof wrap.

CRIs are inexpensive tools. An 8 hour mid-dose rate morphine/lidocaine/ketamine CRI for a 20 kg patient costs the practice less than $1.50 (drug costs).

The suitability of a given drug infusion, as with any analgesic drug use, should be based on a sound understanding of that drug's potential impact on any patient of a given health status. It is beyond the scope of this review to discuss detailed drug suitability issues.