Circulation 84,122 • Volume 24, No. 1 • Spring 2009   Issue PDF

In a Specified Context, Ketamine is Non-Adrenergic and Provides Preemptive Analgesia

Barry L. Friedberg, MD

To the Editor

Dr. Durieux’s article “Does anesthetic management affect cancer outcome?” in the winter 2008-9 APSF Newsletter was really very interesting. However, his non-contextual inclusion of ketamine as a “bad” drug might discourage APSF readers from administering BIS-monitored propofol ketamine (PK) anesthesia1 to their patients. In the context in which Dr. Durieux cites the use of ketamine,2 as well as its historically established reputation,3 it is unquestionably an adrenergic stimulator. However, that context ignores earlier (and later) published work that demonstrates a lack of hypertension, tachycardia, and hallucinations.4-7 These publications demonstrate a context in which ketamine is not an adrenergic stimulator; namely that in which propofol is incrementally titrated to BIS <75 prior to the administration of a 50 mg dissociative dose of ketamine and 2-3 minutes prior to injection or incision.1

BIS monitoring was added to PK anesthesia in 1997. It serves a 2-fold purpose. First, BIS defines a level of propofol sedation at which ketamine can be given without the adrenergic side effects. Second, during the case, it helps the anesthesiologist educate the surgeon (when possible) when the patient requires re-injection of small amounts of local anesthesia, despite the appearance of a blanched field. Conducting a case in this manner prevents the patient from experiencing pain during the initial injection of local and, subsequently, during the surgery itself. This, plus the decreased catecholamine state from the preoperative oral clonidine premedication, sets the stage for minimal postoperative discomfort. Not only is this specific context devoid of adrenergic stimulation, but also it provides the patient with the benefits of preemptive analgesia, avoiding the postoperative pain Dr. Durieux says “may play a very important role in metastasis after cancer surgery.”

Postoperatively, patients receiving BIS/PK MAC have only required oral Tylenol®, Tylenol PM®, or IV Toradol®, even for abdominoplasties, not morphine PCA. No hospital admissions have resulted for unmanageable pain of PONV since inception of PK MAC in 1992. Absent a Level I study to establish reproducibility, BIS/PK MAC has been administered for more than 100 different surgeons over a decade in >2,500 patients. This clinical experience should strongly suggest reproducibility. Other anesthesiologists have also reported similar outcomes when following the clinical pathway referenced herein. Interested readers may access the pertinent algorithms from the home page of my website (

Barry L. Friedberg, MD


  1. Friedberg BL. Propofol ketamine with bispectral (BIS) index monitoring. In: Friedberg BL, ed. Anesthesia in cosmetic surgery. New York: Cambridge University Press, 2007:1-13.
  2. Melamed R, Bar-Yosef S, Shakhar G, et al. Suppression of natural killer cell activity and promotion of tumor metastasis by ketamine, thiopental, and halothane, but not by propofol: mediating mechanisms and prophylactic measures. Anesth Analg 2003;97:1331-9.
  3. White PF, Way WL, Trevor AJ. Ketamine—its pharmacology and therapeutic uses. Anesthesiology 1982;56:119-36.
  4. Friedberg BL. The effect of a dissociative dose of ketamine on the bispectral index (BIS) during propofol hypnosis. J Clin Anesth 1999;11:4-7.
  5. Friedberg BL. Facial laser resurfacing with the propofol-ketamine technique: room air, spontaneous ventilation (RASV) anesthesia. Dermatol Surg 1999;25:569-72.
  6. Friedberg BL, Sigl JC. Clonidine premedication decreases propofol consumption during bispectral index (BIS) monitored propofol-ketamine technique for office-based surgery. Dermatol Surg 2000;26:848-52.
  7. Friedberg BL. The dissociative effect and preemptive analgesia. In: Friedberg BL, ed. Anesthesia in cosmetic surgery. New York: Cambridge University Press, 2007:39-46.