**3. Propofol**

Propofol is a 1,4-diisopropyl quinol with sedative-hypnotic properties. Because of its slight solubility in water, the drug is formulated as an emulsion for clinical use. It is highly lipophilic and distributes extensively in the body. The drug was introduced to the North American market in 1989 and has largely displaced both thiopental and methohexital for induction of general anesthesia and maintenance of sedation.

Propofol's rapid metabolism accounts for its short activity. It is also a potent antiemetic, especially in the absence of concomitant opioid administration. Only after much experience with the drug for sedation was the patients' clear head and happy affect after emergence was this quality appreciated by the author. Unfortunately, these qualities have also made propofol a drug of abuse within small numbers of the profession ("white rabbit") as well as by celebrities like Michael Jackson.

Propofol also results in inhibition of the N-methyl, D-aspartate (NMDA) subtype of glutamate receptor [4]. Lack of recall was observed in 95% of patients at BIS of 77 [5]. Propofol at 25–50 mcg/kg/min was sufficient to produce sedation to 60 < BIS < 75 with baseline EMG for many patients. However, as little as 2.5 mcg/kg/min and as much as 200 mcg/kg/min have been required to achieve the same numerically defined level of sedation at 60 < BIS < 75 with baseline EMG. This 20-year experience represents nearly a hundred-fold variation in propofol requirements. Incrementally inducing patients starting with 50 mcg/kg propofol miniboluses (*Watch YouTube Propofol induction with BIS monitor without instrumenting airway*) allows the anesthesiologist to identify outliers early in the case and enables all patients to receive "not too much, too little, but just the right amount" and not to hear, feel or remember their surgery. The expression "not too much, too little, but just the right amount" is the basis for using the shorthand expression "Goldilocks" anesthesia. Those unfamiliar with the Goldilocks story should watch YouTube Goldilocks and the Three Bears—Fairy Tales.

Textbook doses for propofol sedation do not discuss the value of incremental induction not only to identify outliers but also to dramatically minimize airway management and eliminate precipitous blood pressure drops. Incremental propofol induction more often maintains the airway patency by preserving muscle tone of the *temporalis, masseter, genioglossus* and *orbicularis oris*.

Propofol was introduced to North America in 1989 and quickly replaced both thiopental and methohexital as the preferred induction agent. As a proprietary agent, a 20 cc propofol bottle retailed around \$12–15 USD, making a continuous infusion for surgery apparently prohibitive for multihour surgeries in a cost-conscious office-based cosmetic surgery suite.

After five years of performing propofol ketamine (PK) intravenous sedation using an average three 20 cc bottles of propofol per hour, the author's surgeons kept clamoring for a less expensive way to administer it, especially for 4–6 hours rhytidectomies with or without browlifts, platysmal plications or blepharoplasties. Five years of data on 1264 patients demonstrated no reduction in propofol requirements with either 2 or 4 mg preoperative midazolam as administered [6].

This same paper [6] also published the lowest postoperative nausea and vomiting (PONV) rate (0.6%) in the literature without antiemetic use in an Apfel-defined high-risk patient population, i.e. nonsmoking females with positive PONV and/or motion sickness histories, having emetogenic (cosmetic) surgery. Scrupulous opioid avoidance both during and after surgery has allowed this astounding PONV rate to go unchallenged to date.

Aspect Medical Systems (Aspect Medical Systems, a venture capital company, was purchased by Medtronic that has subsequently been acquired by Covidien) exhibited their bispectral index monitor™ (BIS) for measuring cortical effect at the 1997 International Anesthesia Research Society (IARS) annual meeting in San Francisco. The author was exhibiting his Society for Office Anesthesiologists (SOFA) at the same meeting and was initially exposed to the BIS monitor there. The BIS monitor appeared to offer more promise reducing propofol requirements than previous efforts with midazolam premedication [6]. Later work validated that promise [7, 8]. Entropy™ is another depth of anesthesia monitor but has not been validated in nearly as many clinical papers as BIS [9].
