Target-controlled infusion (TCI) technology is now well established worldwide, except in the United States where it has not been approved by the Food and Drug Administration. TCI provides clinicians the convenience of thinking in terms of target concentrations rather than bolus doses and infusion rates.1 Target-controlled drug delivery is based on ever-advancing pharmacokinetic models,2 enhancing accurate drug delivery, and decreasing variability relative to bolus injection dosing.1
Although popular for total IV anesthesia, TCI shows promise for deep sedation outside the operating room. When compared with intermittent bolus dosing, TCI has shown less respiratory depression in such sedation settings.3,4 This is because TCI infusions typically require less total propofol,5 providing faster recoveries.5 Edwards et al.6 report remarkable safety in the seemingly unimaginable scenario of using nonmedical staff to successfully administer TCI-facilitated propofol sedation to 4342 patients. Although existing pharmacokinetic models are optimized for operating room anesthesia, their specific validation and refinement for procedural sedation are warranted.
Given the safety history of TCI, and the intrinsic safety of carefully titrated propofol infusions, we believe that TCI could improve the safety and efficacy of emergency department procedural sedation. As emergency physicians, we daily encounter anxious patients requiring painful procedures (e.g., fracture reduction, major joint relocation, abscess incision and drainage, arthrocentesis, and laceration repair). We also encounter patients with the variations in physiology handled by the most recent propofol pharmacokinetic models: very young, very elderly, and very obese. Deep rather than moderate sedation is often necessary to humanely accomplish these procedures, especially in children. For the same reason, anesthesiologists choose to sedate with propofol, in our practice propofol is our principal deep sedative, with presedation analgesia achieved with titrated opioids.7–10
Current monitoring modalities detect but do not predict adverse events during procedural sedation. Therefore, there is no objective means to gauge the ongoing risk of ventilatory compromise, making it difficult to know when the patient is at high risk for adverse events. It may be challenging to find an appropriate sedation end point where the patient is able to tolerate the procedure without pain or anxiety while maintaining adequate ventilation.11 Similar to our colleagues in anesthesiology, emergency physicians have adopted rigorous safety precautions, including vigilant monitoring during deep sedation.7,9,10 TCI could potentially enhance the quality and safety of emergency department sedation practice in the following 3 ways.
Lacking TCI, emergency physicians currently administer propofol with intermittent bolus dosing attempting to approximate the steady state achieved by TCI. We estimate the appropriate size of each bolus, as well as the interval between boluses, to obtain a steady drug effect. However, this cannot be done accurately, given that the polyexponetial plasma concentration versus time curve is slightly different after each bolus.
Despite vigilance and continuous monitoring, multiple intermittent boluses lead to multiple peaks and troughs in drug concentration. The peaks do not provide any therapeutic value but are associated with increased risk for respiratory and cardiovascular depression. By using capnography, we see hypopneic hypoventilation and even apnea when propofol peaks are pronounced.9,10 Computerized propofol delivery provides the precision and finesse to smooth these peaks and troughs, thus decreasing the likely frequency, magnitude, and duration of hypoventilation.
ENHANCED PATIENT COMFORT
The intent of deep sedation is to provide consistent patient comfort during a painful and anxiety-inducing procedure. The troughs in drug concentration that result from intermittent bolus dosing can induce periods of suboptimal sedation depth, at times during the most critical parts of the procedure. Smoothing these troughs with TCI could provide a more reliably favorable and tolerable patient experience.
TOTAL MONITORING FOCUS
Regulations in many states prohibit nurses from administering propofol, even when the ordering physician is physically present. As a result, during procedural sedation, emergency physicians often find themselves personally administering intermittent propofol boluses. Adoption of TCI would reduce the physical effort of drug administration to adjusting a target-concentration dial, keeping our eyes more consistently on the patient and monitoring the vital signs. Thus, TCI would better facilitate a total focus on patient monitoring. In the future, TCI could potentially be linked to vital signs as a closed-loop system for adjusting dosage and infusion rate with the use of algorithms that integrate real-time vital sign data with TCI function.
There are disadvantages to TCI. The pumps are expensive. As with any new technology, involved staff need special training in the care and use of the device. During each sedation, a few additional minutes of staff time would be required for set up and pump programming. This might be deemed excessive for a brief painful procedure. There is a small risk of human programming errors, for example, inputting the wrong patient covariates (e.g., age, height, and weight). However, there are also errors associated with bolus drug delivery, as well as errors in programming conventional infusion pumps. A dedicated propofol TCI drug delivery system might be less error-prone than programming a general-purpose infusion pump.
In summary, emergency department deep sedation appears to be an appropriate scenario in which TCI could enhance patient safety, patient comfort, and facilitate safe performance of painful procedures. Once TCI has been approved by the Food and Drug Administration in the United States, the United States community of emergency physicians is ready to undertake the research necessary to confirm or refute this promise.
Name: Steven M. Green, MD.
Contribution: This author helped in concept development, drafting, and critical review.
Attestation: Steven M. Green approved the final manuscript.
Name: Baruch S. Krauss, MD, EdM.
Contribution: This author helped in concept development and extensively editing the manuscript.
Attestation: Baruch S. Krauss approved the final manuscript.
This manuscript was handled by: Steven L. Shafer, MD.
1. Hu C, Horstman DJ, Shafer SL. Variability of target-controlled infusion is less than the variability after bolus injection. Anesthesiology. 2005;102:639–45
2. Eleveld DJ, Proost JH, Cortínez LI, Absalom AR, Struys MM. A general purpose pharmacokinetic model for propofol. Anesth Analg. 2014;118:1221–37
3. Chan WH, Chang SL, Lin CS, Chen MJ, Fan SZ. Target-controlled infusion of propofol versus intermittent bolus of a sedative cocktail regimen in deep sedation for gastrointestinal endoscopy: comparison of cardiovascular and respiratory parameters. J Dig Dis. 2014;15:18–26
4. De Vito A, Agnoletti V, Berrettini S, Piraccini E, Criscuolo A, Corso R, Campanini A, Gambale G, Vicini C. Drug-induced sleep endoscopy: conventional versus target controlled infusion techniques—a randomized controlled study. Eur Arch Otorhinolaryngol. 2011;268:457–62
5. Sakaguchi M, Higuchi H, Maeda S, Miyawaki T. Dental sedation for patients with intellectual disability: a prospective study of manual control versus Bispectral Index-guided target-controlled infusion of propofol. J Clin Anesth. 2011;23:636–42
6. Edwards JA, Kinsella J, Shaw A, Evans S, Anderson KJ. Sedation for oocyte retrieval using target controlled infusion of propofol and incremental alfentanil delivered by non-anaesthetists. Anaesthesia. 2010;65:453–61
7. Godwin SA, Burton JH, Gerardo CJ, Hatten BW, Mace SE, Silvers SM, Fesmire FMAmerican College of Emergency Physicians. . Clinical policy: procedural sedation and analgesia in the emergency department. Ann Emerg Med. 2014;63:247–58
8. Krauss B, Green SM. Procedural sedation and analgesia in children. Lancet. 2006;367:766–80
9. Krauss B, Hess DR. Capnography for procedural sedation and analgesia in the emergency department. Ann Emerg Med. 2007;50:172–81
10. Miner JR, Burton JH. Clinical practice advisory: emergency department procedural sedation with propofol. Ann Emerg Med. 2007;50:182–7
11. Green SM, Mason KP. Reformulation of the sedation continuum. JAMA. 2010;303:876–7