Grunwell JR, Travers C, Stormorken AG, Scherrer PD, Chumpitazi CE, Stockwell JA, Roback MG, Cravero J, Kamat PP. Pediatric Critical Care Medicine, August 2017, vol 18, no 8, pp 356-363.
The combination of propofol and ketamine has emerged as a popular sedation choice in the emergency setting. Ketamine, especially, is used widely in both adult and pediatric emergency departments for procedural sedation (PS). It has proven success with painful procedures such as fracture reduction, abscess drainage, and laceration repair. However, there have been few studies in the pediatric population investigating the safety and efficacy of both ketamine and propofol when used in combination, outside of the emergency department and in operating room locations.
Using data collected from the Pediatric Sedation Research Consortium (PSRC) in this observational study, Grunwell, et al, describe experiences with the combined use of ketamine and propofol (“ketofol”) for procedural sedation outside of the emergency department. The study population received intravenous ketamine plus propofol for PS. Within the PSRC, this population was a subset of sedation encounters receiving intravenous ketamine. Patients were less than 21 years of age. Patients receiving Ketamine in the non-intravenous route (intranasal, intramuscular, ect.) were excluded. The primary outcomes measured were successful completion of a procedure and the occurrence of an adverse event (AE) or serious adverse event (SAE).
The authors’ results showed that between September 2007 and November 2015 there were ~8000 ketamine + propofol sedations reported in the PSRC database. A total of 7,313 met inclusion criteria. Roughly 71% of sedated patients were less than 13 years old. Over 80% of patients were American Society of Anesthesiologists Physical Status (ASA) III or less. 99 percent of patients were nil per os (NPO) for clears greater than two hours and 98% were NPO for solids greater than six hours. Location of ketofol sedations included 76% in a radiology or sedation unit, 11% in an intensive care unit, 5% in a floor or clinic location, 0.4% in a catheterization laboratory, and 0.1% in a dental area. Of the 7,313 sedations, half received other agents in addition to ketofol, most commonly a benzodiazepine. Of all ketofol sedated patients, 716 (10%) experienced at least one adverse event and 254 (3.5%) experienced at least one serious adverse event. The most common serious adverse event was upper airway obstruction (144) followed by emergent airway intervention (118). One patient had a cardiac arrest. Although the total SAE rate was 3.5%, which is overall low, it is higher than the rate of propofol (2.2%) alone or ketamine alone (1.77%), as reported in previous PSRC studies. The overall AE ratio for ketamine and propofol combined was documented to be 9.8% which is nearly double the AE ratio for propofol alone (5%) and nearly 1.5 times the rate for ketamine alone (7.3%) as noted in previous PSRC studies. The most common AE was desaturation, followed by cough. Over 99% of procedures were completed. Over two thirds of the studies were classified as painful procedures.
There are several limitations to this study. First, it is a retrospective study and is observational. Second, there is no data recorded on depth of sedation which can impact both SAE and AE. Third, while the definitions of SAEs are generally well agreed upon, AEs may not be reported consistently by sedation providers. Lastly, the authors acknowledge that it is impossible to know the sequence of ketamine-propofol administration or whether the medications were pre-mixed in the same syringe.
Does this mean that propofol and ketamine can no longer be used in combination? Well, perhaps the practice deserves analysis. The authors raise the key point that the overall SAE rate is higher for ketamine-propofol combined than for either sedation option alone. They also mention that two-thirds of the procedures studied were documented as painful. So why use two medications when you can choose one? Green et al has presented both the positives and the negatives in his 2015 article. Some noteworthy advantages of “ketofol” include combining the analgesic effects of ketamine and propofol. Additionally, the anti-emetic properties of propofol often offset ketamine associated emesis and ketamine may also blunt the hypotensive effects of propofol. However, there seems to be no compelling evidence that there is superior sedation with the ketamine-propofol combination. Furthermore, using two sedation medications often adds complexity to the sedation plan.
The article abstract can be found via the link on our blog, www.pedzzzz.com.
References:
- Grunwell JR, Travers C, Stormorken AG, Scherrer PD, Chumpitazi CE, Stockwell JA, Roback MG, Cravero J, Kamat PP. “Pediatric Procedural Sedation Using the Combination of Ketamine and Propofol Outside of the Emergency Department.” Pediatric Critical Care Medicine, August, 2017, vol 18, no. 8, pp. 356-363.
- Green, SM, Andolfatto, G, Krauss, BS. “Ketofol for Procedural Sedation Revisited: Pro and Con.” Annals of Emergency Medicine, vol. 65, no. 5, 2015, pp. 489–491.
Carmen D. Sulton, MD
Assistant Professor of Pediatrics and Emergency Medicine
Emory University School of Medicine
Atlanta, GA
Laurie Burton, MD
Assistant Professor of Pediatrics and Emergency Medicine
Emory University School of Medicine
Atlanta, GA
Pradip Kamat, MD, MBA, FCCM
Associate Professor of Pediatrics
Emory University School of Medicine
Director Children’s Sedation services at Egleston
Atlanta, GA
Jason Reynolds, MD
Assistant Professor of Pediatrics
Section of Pediatric Sedation
Baylor College of Medicine
San Antonio, TX
Patricia Scherrer, MD
Associate Professor of Pediatrics
Section of Pediatric Sedation
Baylor College of Medicine
San Antonio, TX
