**4. Ketamine**

ketamine administration. No tachycardia or hypertension was observed when ketamine was administered well prior to the lidocaine with epinephrine solution injection. Nontriggering

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

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

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

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 prohibi-

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

tive for multihour surgeries in a cost-conscious office-based cosmetic surgery suite.

should watch YouTube Goldilocks and the Three Bears—Fairy Tales.

"Goldilocks'" anesthesia also means surgical facilities need not stock dantrolene.

**3. Propofol**

like Michael Jackson.

general anesthesia and maintenance of sedation.

44 Anesthesia Topics for Plastic and Reconstructive Surgery

In the 1950s, postoperative pain was treated with morphine or meperidine, often undertreated for two reasons: (a) fear of producing opioid addiction and (b) problems of overtreatment, respiratory insufficiency or apnea and death. Naloxone was not introduced until 1971 and pulse oximetry became commercially available in 1983.

The researchers of the day postulated that, if another class of drugs could be developed that would ameliorate pain without respiratory depression, patients could be better treated for postoperative pain with neither under- nor overtreatment.

The first class of drugs explored was the phencyclidines. The parent compound, phencyclidine phosphate, was marketed as Serenyl® by Parke-Davis in 1958 but was quickly withdrawn from the market because of the high percentage of undesirable side effects, i.e. hallucinations, mania, delirium and disorientation. Later, phencyclidine phosphate, as a drug of abuse, became better known by the initials, PCP or "angel dust."

The researchers did not give up quickly on the phencyclidine class. They began experimenting with a modified PCP molecule, ketamine, which received FDA approval in humans in 1971. The drug, like its predecessor, was introduced as the "silver bullet," a complete, total intravenous agent, meaning no other agents were needed. Because it supported both respiration and blood pressure, ketamine quickly gained a reputation as a safe drug but one not good for adult patients. It did become popular in children's burn units, especially for the extremely painful dressing changes.

During the author's anesthesia residency at Stanford 1975–1977, he was introduced to administering ketamine in small doses (10–20 mg IV) prior to positioning elderly patients about to receive spinal anesthesia for surgery on femoral head or shaft fractures. Elderly patients were not particularly susceptible to ketamine-associated hallucinations or dysphorias. Veterinarians also adopted ketamine, quickly realizing that it was nearly impossible to kill an animal, even if the per body weight dose was more than twice the recommended amount. Also, the animals did not complain about hallucinations. While ketamine was a safe drug, two generations of human anesthesiologists have avoided its use in adult day surgery. Sometime during the mid-1970s, a Las Vegas plastic surgeon, Charles Vinnik, wearied listening to his patients cry out when he injected local anesthesia under his self-directed diazepam and meperidine IV sedation. Even though the patients had amnesia for the experience, the patients' cries were distressing to the OR staff. Vinnik asked his anesthesiologist if there was anything else he could use that would eliminate the distressing reactivity of the patients. Ketamine was suggested. Ketamine was first synthesized by Stevens in 1962 and first used in humans by Domino and Corssen in 1965. The drug was used in clinical practice barely 5 years when its use was suggested to Vinnik.

ability of the BIS monitor to accurately measure propofol. This study compared ketamine doses of 0.2–0.5 mcg/kg and concluded 0.5 mcg/kg would defeat the BIS [14]. An earlier publication using **50 mg ketamine, independent of body weight**, confirmed BIS' utility [15]. More controversial is the author's use of **50 mg ketamine** *independent* **of body weight**. Brain weight does not vary with body weight (i.e. the brain weight of a 100-kg male is not twice that of a 50-kg female). The midbrain is a very small portion of the total brain weight. The NMDA receptors are a small part of the very small midbrain. After observing the same immobility (or dissociative effect) in 100-kg males as in 50-kg females, body weight was not deemed a consideration for effective ketamine dose. With the addition of BIS/EMG monitoring, absence of EMG spike is considered numerically reproducible evidence of NMDA saturation and nono-

Brain Monitored Propofol Ketamine for Elective Cosmetic Surgery

http://dx.doi.org/10.5772/intechopen.71442

47

In many third world countries, ketamine infusions are still to be found as the drug was originally marketed. However, as propofol has become generic and very inexpensive, more anesthesia providers from third world countries have accessed the author's web site to obtain

Ketamine, ironically, is the perfect adjuvant drug (or the 'olive' in the propofol 'martini') not the complete and total intravenous agent its makers originally intended it to be, at least in the

Brain monitored PK IV sedation is less expensive, safer and simpler and gives better outcomes (i.e. virtually no PONV [16] and minimal postoperative pain). With ability to stratify anesthesia outcomes by depth of anesthesia and the negative effects of routine anesthesia overmedication (i.e. BIS <45), studies have demonstrated more apparent negative effects from this practice [17–20]. Postoperative cognitive dysfunction (POCD) is the name for the pseudo-Alzheimer's type of confusion seen more often in elderly, rhytidectomy patients. Sometimes this lasts hours, days, weeks or months. Sometimes the effects are not transitory. Rapid emergence does not preclude intraoperative overmedication. Patients are left with the long-term

The brain monitored PK IV sedation technique also gives providers the ability to refrain from the nefarious practice of routinely overmedicating patients for fear of undermedicating them.

**5. Putting brain monitored propofol ketamine ("Goldilocks") anesthesia** 

Along with the patient, many egos enter the operating room, not the least of which is that of the surgeon's. The surgeon's cooperation with local anesthesia is essential for success. The surgeon must also understand the need for *adequate* local anesthesia. **Surgeon perfection injecting local analgesia is not a requirement, only persistence.** Surgeons typically

*Daniel HS Lin, DO, Cosmetic surgeon*

pioid, preemptive analgesia.

western world.

**into practice**

information with which to execute the PK paradigm.

consequences of their anesthesiologist's short-term care.

*Teaching the technique is simple. Teaching cooperation is not.*

Through trial and error, Vinnik came upon his initial ketamine dose of 75 mg independent of body weight to prevent the patients from either moving or crying out after they were rendered sleepy from incremental doses of intravenous diazepam. Vinnik began with his test dose of 10 mg diazepam administered through an external jugular (to avoid venous thrombosis), followed by 5–10 mg increments to a total of 25–50 mg. Vinnik had his patients engage a 24-hour nurse to observe them after discharge to home. His cost-effective concept meant the cost of the recovery nurse did not come from him.

Although Vinnik published his diazepam-ketamine technique (i.e. **hypnosis first, then dissociation**) without the reported hallucinations or dysphorias, the 1981 paper appeared in the plastic surgery literature [10]. Vinnik's approach lay largely unnoticed in the anesthesia community until the author heard him speak in Newport Beach, CA, in December 1991, later visiting his office operating room in March 1992.

The author considered Vinnik's use of ketamine useful but doubted diazepam would be an optimal drug for day cases expected to return to home. Propofol was then considered as an alternative to diazepam for hallucination-blocking purpose. Searching the anesthesia literature to support this use of propofol turned up no useful information. March 26, 1992 was the beginning of this author's clinical trial of propofol followed by ketamine [11]. In the 1990s, ketamine became a drug of abuse, a "rave" drug and later lumped together with flunitrazepam and gamma hydroxybutyrate (GHB) as "date rape" drugs. Ketamine is also a drug of abuse. Heavy users can develop long-term bladder or urinary tract damage and incontinence.

Anesthesia trainees continue to be taught ketamine causes tachycardia, hypertension and hallucinations despite the knowledge that benzodiazepines [12] or propofol hypnosis blocks ketamine hallucinations [13]. In the pre-BIS era, loss of lid reflex and loss of verbal response defined adequate hallucination-blocking depth of propofol hypnosis. With real-time BIS/ EMG monitoring, the level of hallucination-blocking propofol hypnosis is more numerically defined as 60 < BIS < 75 with baseline EMG. Some believe the use of ketamine defeats the ability of the BIS monitor to accurately measure propofol. This study compared ketamine doses of 0.2–0.5 mcg/kg and concluded 0.5 mcg/kg would defeat the BIS [14]. An earlier publication using **50 mg ketamine, independent of body weight**, confirmed BIS' utility [15].

During the author's anesthesia residency at Stanford 1975–1977, he was introduced to administering ketamine in small doses (10–20 mg IV) prior to positioning elderly patients about to receive spinal anesthesia for surgery on femoral head or shaft fractures. Elderly patients were not particularly susceptible to ketamine-associated hallucinations or dysphorias. Veterinarians also adopted ketamine, quickly realizing that it was nearly impossible to kill an animal, even if the per body weight dose was more than twice the recommended amount. Also, the animals did not complain about hallucinations. While ketamine was a safe drug, two generations of human anesthesiologists have avoided its use in adult day surgery. Sometime during the mid-1970s, a Las Vegas plastic surgeon, Charles Vinnik, wearied listening to his patients cry out when he injected local anesthesia under his self-directed diazepam and meperidine IV sedation. Even though the patients had amnesia for the experience, the patients' cries were distressing to the OR staff. Vinnik asked his anesthesiologist if there was anything else he could use that would eliminate the distressing reactivity of the patients. Ketamine was suggested. Ketamine was first synthesized by Stevens in 1962 and first used in humans by Domino and Corssen in 1965. The drug was used in clinical practice barely 5 years

Through trial and error, Vinnik came upon his initial ketamine dose of 75 mg independent of body weight to prevent the patients from either moving or crying out after they were rendered sleepy from incremental doses of intravenous diazepam. Vinnik began with his test dose of 10 mg diazepam administered through an external jugular (to avoid venous thrombosis), followed by 5–10 mg increments to a total of 25–50 mg. Vinnik had his patients engage a 24-hour nurse to observe them after discharge to home. His cost-effective concept meant the

Although Vinnik published his diazepam-ketamine technique (i.e. **hypnosis first, then dissociation**) without the reported hallucinations or dysphorias, the 1981 paper appeared in the plastic surgery literature [10]. Vinnik's approach lay largely unnoticed in the anesthesia community until the author heard him speak in Newport Beach, CA, in December 1991, later

The author considered Vinnik's use of ketamine useful but doubted diazepam would be an optimal drug for day cases expected to return to home. Propofol was then considered as an alternative to diazepam for hallucination-blocking purpose. Searching the anesthesia literature to support this use of propofol turned up no useful information. March 26, 1992 was the beginning of this author's clinical trial of propofol followed by ketamine [11]. In the 1990s, ketamine became a drug of abuse, a "rave" drug and later lumped together with flunitrazepam and gamma hydroxybutyrate (GHB) as "date rape" drugs. Ketamine is also a drug of abuse. Heavy users can develop long-term bladder or urinary tract damage and incontinence. Anesthesia trainees continue to be taught ketamine causes tachycardia, hypertension and hallucinations despite the knowledge that benzodiazepines [12] or propofol hypnosis blocks ketamine hallucinations [13]. In the pre-BIS era, loss of lid reflex and loss of verbal response defined adequate hallucination-blocking depth of propofol hypnosis. With real-time BIS/ EMG monitoring, the level of hallucination-blocking propofol hypnosis is more numerically defined as 60 < BIS < 75 with baseline EMG. Some believe the use of ketamine defeats the

when its use was suggested to Vinnik.

46 Anesthesia Topics for Plastic and Reconstructive Surgery

cost of the recovery nurse did not come from him.

visiting his office operating room in March 1992.

More controversial is the author's use of **50 mg ketamine** *independent* **of body weight**. Brain weight does not vary with body weight (i.e. the brain weight of a 100-kg male is not twice that of a 50-kg female). The midbrain is a very small portion of the total brain weight. The NMDA receptors are a small part of the very small midbrain. After observing the same immobility (or dissociative effect) in 100-kg males as in 50-kg females, body weight was not deemed a consideration for effective ketamine dose. With the addition of BIS/EMG monitoring, absence of EMG spike is considered numerically reproducible evidence of NMDA saturation and nonopioid, preemptive analgesia.

In many third world countries, ketamine infusions are still to be found as the drug was originally marketed. However, as propofol has become generic and very inexpensive, more anesthesia providers from third world countries have accessed the author's web site to obtain information with which to execute the PK paradigm.

Ketamine, ironically, is the perfect adjuvant drug (or the 'olive' in the propofol 'martini') not the complete and total intravenous agent its makers originally intended it to be, at least in the western world.

Brain monitored PK IV sedation is less expensive, safer and simpler and gives better outcomes (i.e. virtually no PONV [16] and minimal postoperative pain). With ability to stratify anesthesia outcomes by depth of anesthesia and the negative effects of routine anesthesia overmedication (i.e. BIS <45), studies have demonstrated more apparent negative effects from this practice [17–20]. Postoperative cognitive dysfunction (POCD) is the name for the pseudo-Alzheimer's type of confusion seen more often in elderly, rhytidectomy patients. Sometimes this lasts hours, days, weeks or months. Sometimes the effects are not transitory. Rapid emergence does not preclude intraoperative overmedication. Patients are left with the long-term consequences of their anesthesiologist's short-term care.

The brain monitored PK IV sedation technique also gives providers the ability to refrain from the nefarious practice of routinely overmedicating patients for fear of undermedicating them.
