Waking up from propofol

Colonoscopy patients prefer propofol over fentanyl/midazolam

SEATTLE – As patient satisfaction becomes increasingly important for reimbursements, it might be a good idea to switch to propofol for colonoscopies.

The reason is because patients prefer propofol over standard-of-care fentanyl/midazolam as their anesthetic for outpatient colonoscopies, according to a randomized, blinded trial at a single center. Importantly, clinical assessment also showed that propofol outperformed fentanyl/midazolam in terms of hypoxia, pain, nausea, and procedural difficulties.

Copyright Eraxion/Thinkstock The 300 patients randomized to propofol were more likely than were the 300 randomized to fentanyl/midazolam to rate the amount of anesthesia they received as being “just right” (98.7% versus. 91.3%), and they were more likely to state that they were “very satisfied” with their anesthesia during the procedure (86.3% versus 74%). Propofol patients were also more likely to recommend their anesthesia to others (98.7% versus 94%).

“Our study demonstrated the superiority of propofol over fentanyl/midazolam in an outpatient setting from both a patient satisfaction standpoint and from a provider prospective,” said lead investigator Anantha Padmanabhan, MD, a colorectal surgeon with Mount Carmel Health, Columbus, Ohio.

The short duration of action and quick turnaround time have led to an increase in the use of propofol for outpatient procedures. It’s been studied extensively for safety and efficacy, but patient preference has not been well documented. The investigators wanted to look into the issue because patient satisfaction has become an important metric for reimbursement, Dr. Padmanabhan said at the annual meeting of the American Society of Colon and Rectal Surgeons, where the study was presented.

Patients were randomly assigned to propofol or fentanyl/midazolam in the colonoscopy suite at the Taylor Station Surgical Center in Columbus. Anesthesia personnel administered the assigned anesthetic, and circulating nurses rated the difficulty of the procedure. Patients were surveyed after they came to, and again over the phone at least 24 hours after discharge.

Alex Otto/Frontline Medical News

Dr. Anantha Padmanabhan

Dr. Padmanabhan performed all the colonoscopies in the study. He could not be completely blinded to the anesthetic used, so did not participate in any data collection.

Fewer propofol patients reported pain greater than zero during the procedure (2% versus 6%); fewer remembered being awake (2% versus 17%); and fewer had complications (2.7% versus 11.7%); 21 patients in the fentanyl/midazolam group had intraoperative hypoxia, versus 1 in the propofol group. Eleven fentanyl/midazolam patients had postprocedure nausea and vomiting, versus one propofol patient.

Nurses rated 26% of fentanyl/midazolam procedures as “difficult,” compared to 4.7% in the propofol group. Mean induction time was 2.1 minutes with propofol and 3.2 minutes with fentanyl/midazolam; mean procedure time was about 13 minutes in both groups. The cecal intubation rate was 100% in both groups, and there were no perforations.

Propofol patients reacted less during the procedure; an audience member wondered if the loss of feedback was a problem for Dr. Padmanabhan.

“We use propofol in a very light sedation, and sometimes we do get feedback, but more importantly we feel the technique of colonoscopy is as much by feel as it is by vision. If you feel that the scope is not going in correctly, you should pull back then try the loop reduction maneuvers,” he said.

The most common indication for colonoscopy was a history of polyps, followed by general colon screening. Patients in both groups were a mean of 61 years old, and about evenly split between the sexes. Body mass index was a mean of 30 kg/m2 in both groups. There were no between-group differences in comorbidities; hypertension and diabetes were the most common.

There was no external funding for the work, and the investigators had no disclosures.

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Introduction

An adequate level of patient sedation allows for thorough and relaxed endoscopic procedures and is desirable for the successful performance of a safe and high-quality colonoscopy. Historically, sedation was induced and maintained mainly by a combination of a benzodiazepines and opioids (Bdz–O), which ensured a mild–moderate level of sedation; however, more recently propofol-mediated sedation has been introduced as a reasonable alternative for sedation, due to its pharmacokinetic and pharmacodynamic properties, which facilitate rapid onset of action and recovery, as well as its favorable safety profile.1,2 Traditionally, propofol is administered by anesthesiologists, but due to its increasing use within endoscopy units, programs have been developed for nonanesthesia sedationists to use propofol sedation during endoscopy procedures, typically with the sedation being given by trained endoscopists or nurses.

Several studies have demonstrated that propofol-mediated sedation is well tolerated and associated with faster recovery and discharge times compared with Bdz–O sedation, without an increase in adverse events.3–6 In addition, patient satisfaction appears to be greater for those undergoing a colonoscopy who receive propofol-mediated sedation,7 and this finding may improve patient compliance and adherence to colorectal cancer-screening and -surveillance programs.

The level of sedation under propofol-mediated sedation increases in a dose-dependent manner, and patients are generally titrated to an adequate level of sedation as required during the procedure,8 which may improve the efficiency and quality of the procedure by providing the endoscopist with optimal conditions for a thorough visualization, while eliminating any distraction due to an uncomfortable patient. This may be translated into an enhanced adenoma/polyp-detection rate, a premier colonoscopy-quality indicator. Moreover, the more comfortable and sedated a patient is, the higher the likelihood that cecal or terminal ileum intubations can be performed, especially in technically difficult cases.9,10 An assessment of the effect of propofol-mediated sedation on the outcome of a procedure, namely colonoscopy-quality measures, may be of paramount importance in justifying its widespread use, as controversy remains regarding the limitations concerning the setting and personnel certified to provide propofol-mediated sedation.

Methods

We conducted a large retrospective cohort study that examined consecutive patients who had undergone a colonoscopy over a 15-year period within the Gastroenterology Department at the Hillel Yaffe Medical Center, a university-affiliated hospital in Israel. All patient data were collected from the department’s electronic record system, and only patients who had undergone sedated colonoscopies and had a full data set, including demographic details (age, sex), procedural setting (inpatient/outpatient), indication for exam, type and dose of sedation, quality of bowel preparation, depth of examination, and endoscopic findings, were included in the final analysis. Patients under the age of 18 years and those who had undergone prior colon resection were excluded. All patients included in the study were unselectively offered propofol-mediated or standard sedation, based mainly on performer or patient preference/experience.

Patients were divided into two groups, with all those who had been sedated using Bdz–O (midazolam/fentanyl) alone or in combination (directed by the endoscopist), representing the control group, and those who underwent propofol-mediated sedation (propofol alone or in combination with Bdz, directed either by the anesthesiologist or the endoscopist) constituting the study (propofol) group.

Polyp-detection rate, cecal intubation rate, and terminal ileum-intubation rate were examined and compared between the sedation groups and also for a subgroup analysis of patients with adequate bowel preparation only. In the propofol-sedation group, an assessment was made of the correlation between dose and examination outcome. In the same group, examination outcomes for anesthesiologist-administered propofol-mediated sedated colonoscopies were compared to endoscopist-guided propofol-mediated sedation procedures. Moreover, we compared examination outcomes for propofol-only sedation with balanced propofol sedation (use of propofol in addition to Bdz–O). A multivariate analysis was performed to adjust for the potential confounders of age, sex, quality of bowel preparation, procedural setting (outpatient/inpatient), and indications. This study was approved by the Hillel Yaffe Medical Center’s local ethics committee.

Statistical analysis

Descriptive statistics in terms of means ± SD and percentages are presented for the different parameters examined. Differences between the two groups (propofol group vs control group) were compared using Fisher’s exact test for categorical parameters and t-tests for quantitative parameters. ORs and 95% CIs were also used to analyze the differences between the two groups. Several multivariate logistic regression models were employed to determine the effect of the independent parameters associated with the polyp-detection rate, as well as terminal ileum- and cecal intubation rates. SPSS version 25 was used for the statistical analysis, and P<0.05 was considered significant.

Results

The records of 44,794 patients who had undergone a sedated colonoscopy at our hospital over a 15-year period (2003–2018) were examined. Colonoscopies were performed using propofol-mediated sedation in 16,992 patients (37.9%), and these patients were classified as the propofol group. In total, 15,474 (91%) of these patients received endoscopist-directed propofol-mediated sedation, 3,012 (17.6%) patients propofol-monotherapy sedation, and in 12,462 (73.4%) patients propofol combination with Bdz–O, while in 1,518 patients (9%) propofol was administered by an anesthesiology provider. The control group consisted of 27,802 patients (62.1%) who received Bdz–OP-mediated, endoscopist-directed sedation during their colonoscopy.

Table 1 Baseline characteristics of the propofol and control sedation groups

Abbreviations: CRC, colorectal cancer; FOBT, fecal occult blood test; IBD, inflammatory bowel disease.

Table 2 Endoscopic findings in both sedation groups

Figure 1 Correlations between propofol dose and colonoscopy-quality indicators.

Notes: Propofol monotherapy improved colonoscopy-quality indicators in a dose-dependent manner. *P<0.01; **P<0.01.

Discussion

Cecal intubation and polyp-detection rates are considered among the most important quality indicators of colonoscopy and key measures of a quality procedure.11 Together with terminal ileum-intubation rates, these indicators can reliably predict an examination’s outcome and an endoscopist’s performance. In the current study, a large cohort of patients were included who had undergone colonoscopy procedures after being sedated with propofol-mediated sedation or Bdz–O, in order to compare the sedation-related influence on procedure outcome and performance. As these quality indicators could be affected by patient demographics, bowel-preparation quality, procedure timing (inpatient/outpatient), and indication, these parameters were noted and a multivariate analysis performed to neutralize their possible effect as confounders.

The current study demonstrated a potential positive effect of propofol-mediated sedation on quality indicators and enhanced endoscopist performance compared to standard sedation. Propofol-mediated sedation was significantly associated with an enhanced polyp-detection rate, increased cecal intubation rate, and was associated with the performance of a greater number of terminal ileum intubations. To the best of our knowledge, this is the first study to demonstrate such a positive association between propofol-mediated sedation and colonoscopy outcomes.

In a study by Wang et al,12 which compared mild–moderate sedation with Bdz–O to deeper sedation levels with propofol, it was reported that it was 25% more likely to detect an advanced lesion with propofol-mediated sedation. However, Thirumurthi et al13 demonstrated that deep sedation achieved via propofol did not significantly improve the polyp-detection or cecal intubation rate in initial average risk-screening colonoscopies compared to moderate sedation. Other studies have similarly provided conflicting results, mainly reporting no apparent difference in the overall polyp-detection rate or cecal intubation rate.14–16

In recent years, endoscopist-directed propofol-mediated sedation has been practiced safely and widely, and there is a growing body of evidence that demonstrates this practice to be safe, with no statistically significant increases in adverse events compared to other sedation regimens.17 Moreover, propofol-mediated sedation may boost surveillance and screening programs, as it has been found to be clearly associated with improved patient satisfaction.18 However, despite these advantages, the recent trend toward increased anesthesia involvement in endoscopic procedures, the increased cost, the numerous constraints issued by several gastroenterology and anesthesiology societies, and regional regulations on propofol-mediated sedation utilization during colonoscopies may limit the use of propofol. The American Society of Anesthesiologists and other anesthesiology societies continue to maintain that propofol-mediated sedation should be managed only by anesthesia providers,19–21 yet according to the recent guidelines issued by the American Society for Gastrointestinal Endoscopy on sedation and anesthesia during a gastrointestinal endoscopy, endoscopist use of propofol-based sedation is recommended when it is expected to improve a patient’s safety and comfort and procedural efficiency.22

Many endoscopists believe that patient satisfaction regarding the use of propofol is not sufficient to justify its routine use in endoscopic procedures without an established effect on the procedure’s outcomes and efficiency. Therefore, our study’s findings suggesting a possible favorable effect on colonoscopy performance and outcome are of paramount importance and should be taken into account when determining the policy for sedation during colonoscopies. Given the favorable safety profile and patient satisfaction, our findings may support the adoption of propofol-mediated sedation as the sedation of choice during colonoscopy procedures, and this may help ease the regulations and constraints limiting its use. However, prospective and randomized trials are needed to support and confirm these findings.

In the current study, a subgroup analysis of the propofol-mediated sedation group focusing on propofol monotherapy demonstrated a direct dose-dependent association with endoscopic findings and performance (Figure 1). Therefore, dose limitation is not advisable, and monitoring the level of consciousness and patient discomfort should be performed continuously throughout the procedure, with the dose titrated accordingly to maintain the level of sedation. Moreover, a further subgroup analysis showed that balanced propofol sedation (use of propofol in addition to Bdz–O) did not improve quality indicators compared to propofol monotherapy. While balanced propofol sedation is preferred, as it reduces the risk of oversedation according to some reports,22,23 in our experience propofol monotherapy is easily handled, less associated with respiratory depression, and enables predictable and rapid recovery.

In this study, we have demonstrated that propofol-mediated sedation administered by an anesthesia provider was associated with a significantly enhanced polyp-detection rate, but was associated with lower cecal intubation and terminal ileum-intubation rates compared to endoscopist-directed propofol-mediated sedation. Potential advantages of anesthesia provider–administered sedation may include improved monitoring and decreased distractions for endoscopists. However, anesthesiology-service involvement increases the cost of a procedure and may not be warranted in low-risk patients and procedures, as several studies have demonstrated that there is no added safety benefit.24,25

Limitations

This study has limitations inherent in its retrospective nature. Other confounders influencing the quality indicators, such as endoscopists’ experience and withdrawal times, were not included, and these may have affected the results. Moreover, the size of polyps and their histological data were not considered. Although the adenoma-detection rate is judged to be more reliable and has been widely studied, we preferred to use the polyp-detection rate, as it is easily utilized and was readily available from the colonoscopy reports, obviating the need for incorporating endoscopy and pathology reports. The current study was not designed to address safety issues associated with propofol-mediated sedation, as this has been studied extensively and validated in previous studies, as discussed earlier.17

Conclusion

Our study demonstrates that propofol-mediated sedation use is associated with enhanced colonoscopy-quality indicators. However, large prospective or randomized control trials are warranted to confirm these findings.

Ethical approval

The study protocol conformed with the ethical guidelines of the 1980 Declaration of Helsinki and was approved by the Hillel Yaffe Medical Center Ethics Committee (0013-18HYMC). The committee waived the need to obtain consent for the collection, analysis, and publication of the retrospectively obtained and anonymized data for this noninterventional study.

Acknowledgments

The authors received no financial support for the research, authorship, and/or publication of this article.

Disclosure

The authors report no conflicts of interest in this work.

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Sipe BW, Scheidler M, Baluyut A, Wright B. A prospective safety study of a low-dose propofol sedation protocol for colonoscopy. Clin Gastroenterol Hepatol. 2007;5(5):563–566.

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Ramsay MAE, Newman KB, Jacobson RM, et al. Sedation levels during propofol administration for outpatient colonoscopies. Proc. 2014;27(1):12–15.

Bannert C, Reinhart K, Dunkler D, et al. Sedation in screening colonoscopy: impact on quality indicators and complications. Am J Gastroenterol. 2012;107(12):1837–1848.

Radaelli F, Meucci G, Sgroi G, Minoli G, Italian Association of Hospital Gastroenterologists (AIGO). Technical performance of colonoscopy: the key role of sedation/analgesia and other quality indicators. Am J Gastroenterol. 2008;103(5):1122–1130.

Rex DK, Schoenfeld PS, Cohen J, et al. Quality indicators for colonoscopy. Gastrointest Endosc. 2015;81(1):31–53.

Wang A, Hoda KM, Holub JL, Eisen GM. Does level of sedation impact detection of advanced neoplasia? Dig Dis Sci. 2010;55(8):2337–2343.

Thirumurthi S, Raju GS, Pande M, et al. Does deep sedation with propofol affect adenoma detection rates in average risk screening colonoscopy exams? World J Gastrointest Endosc. 2017;9(4):177–182.

Paspatis GA, Tribonias G, Manolaraki MM, et al. Deep sedation compared with moderate sedation in polyp detection during colonoscopy: a randomized controlled trial. Colorectal Dis. 2011;13(6):e137–e144.

Nakshabendi R, Berry AC, Munoz JC, John BK. Choice of sedation and its impact on adenoma detection rate in screening colonoscopies. Ann Gastroenterol. 2016;29(1):50–55.

Metwally M, Agresti N, Hale WB, et al. Conscious or unconscious: the impact of sedation choice on colon adenoma detection. World J Gastroenterol. 2011;17(34):3912–3915.

Wang D, Chen C, Chen J, et al. The use of propofol as a sedative agent in gastrointestinal endoscopy: a meta-analysis. PLoS One. 2013;8(1):e53311.

Singh H, Poluha W, Cheung M, et al. Propofol for sedation during colonoscopy. Cochrane Database Syst Rev. 2008;(4):CD006268.

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What Are My Options for Sedation During My Upcoming Colonoscopy?

Many people are nervous about getting a colonoscopy performed. The most common concerns are the preparation, the need to take time off from work, finding out that they might have cancer, embarrassment and pain during the procedure. This prevents many individuals from having the very procedure that could save their lives.

While most people know that there have been great improvements in the cleansing preparations (less volume, better taste), and less time off from work (open access colonoscopy eliminates the office visit needed prior to the examination), very few people know much about the types of sedation that are available.

First, it will be helpful to define the various levels of sedation that are possible.

  • None. That means that no medications are given. ‘Nuf said. Very few people choose this option.
  • Light sedation. This is just what it sounds like. Although one is sleepy, the patient can still respond to verbal commands and can feel pain. There is no effect on breathing or cardiovascular function.
  • Moderate sedation (also called Conscious Sedation). This is a little deeper than light sedation, yet the patient can respond purposefully to verbal or physical stimulation. There is usually little or no effect on ventilation or cardiovascular function (low risk). Most patients will have no memory of the procedure while under moderate sedation.
  • Deep sedation. This is deeper still, and patients will respond to repeated painful stimulation, but usually non-purposefully. Breathing may be impaired, as may cardiovascular function. The patient will have no memory of what happened while under deep sedation (amnesia).
  • General anesthesia. In this case, the patient does not respond to painful stimulation at all. Breathing is usually impaired, and airways support and ventilation are usually needed (e.g., a tube placed in the lungs and a ventilator machine providing air). Cardiovascular function may be impaired as well.

The level of planned anesthesia determines who will be administering the sedation. For example, light or moderate sedation are usually administered by the gastroenterologist performing the procedure. Deep sedation and general anesthesia are administered by a nurse anesthetist or anesthesiologist.

Most patients tell me that they want to be totally asleep during the procedure (“Just knock me out, Doc.”) That would mean general anesthesia. But this level has a higher risk for a complication, so when I explain the options, most patients are agreeable to a lower level of anesthesia.

Pros and Cons of Different Levels of Sedation for Colonoscopy

  • None. I perform totally unsedated colonoscopy about once or twice a month. This is in patients who – for various reasons – do not want any sedation. The big advantage is that the patient recovers immediately after the procedure and can go to work or drive right away. They do not need anyone to accompany them home. It also eliminates the possible complications that can occur with any form of anesthesia. While the procedure itself can cause some cramping or gassy abdominal pain, this can be minimized through the use of carbon dioxide to inflate the colon and special techniques to advance the scope. If you want this, make sure that the gastroenterologist has experience doing unsedated colonoscopy. You don’t want to be the doctor’s first one!
  • Light sedation. This is rarely done. Since medications are administered, the risk of complications is present. Also, the patient will need to be accompanied home and should not do regular activities until the next day. But since the sedation is light, there is no effect on pain –the patient feels and remembers everything.
  • Moderate sedation. This is one of the most common forms of sedation used. The medications are usually midazolam and fentanyl – a mild sedative and a pain killer. This is a nice, safe combination, and usually causes amnesia for the procedure. The risk is if too much is given. To avoid this, it is given slowly, with appropriate monitoring. At Temple University Hospital, the doctor and a nurse are with the patient the whole time. The vast majority of patients are satisfied with this sedation.
  • MAC. This stands for Monitored Anesthesia Care. It is administered by an anesthesia professional who is in the room with the gastroenterologist and a nurse or technician. This is usually selected when there are concerns about the patient’s lungs, heart, or tolerance to midazolam or fentanyl. The medicine used for this type of sedation is propofol – yes, the same medicine that was abused by Michael Jackson. However, unlike Michael Jackson, the propofol for colonoscopy is given by a trained professional under constant supervision and monitoring. The depth of sedation with MAC is sometime moderate sedation, but is usually deep sedation.
  • General anesthesia. This is almost never used for colonoscopy. General anesthesia is usually reserved for patients with severe lung disease, unstable airways, and particularly long procedures.

So How Do I Decide What Type of Sedation I Should Get for My Colonoscopy?

It’s simple – talk to your doctor. If you are meeting with the gastroenterologist before the procedure, simply ask what type of sedation is planned. Discuss the pros and cons, and of course, your preferences and concerns. If you are scheduled for open access colonoscopy, you can call the office of the gastroenterologist prior to the procedure to see what is planned. If you want to discuss the sedation further, you should be able to speak with a nurse or doctor prior to the procedure to allay your concerns.

While we can’t make the bowel preparation more pleasant, we certainly can make the actual procedure a comfortable one.

Ready to Schedule Your Colonoscopy?

Schedule a colonoscopy with a Temple gastroenterologist by filling out the Schedule Appointment form or by calling 800-TEMPLE-MED (800-836-7536).

Is Anesthesia A Luxury During Colonoscopy?

No anesthesia here: A patient watches his colonoscopy as it happens at Memorial Sloan-Kettering Hospital in New York. Ted Thai/Time & Life Pictures/Getty Image hide caption

toggle caption Ted Thai/Time & Life Pictures/Getty Image

Doctors often let patients decide how much sedation they’d like when they have a colonoscopy.

But whether you’re put under by an anesthesiologist may depend a lot more on where you live and who gets paid than patient preference, according to a new study.

Big bucks are involved. It would cost an extra $8 billion a year if anesthesia services were used for all 20 million endoscopies and colonoscopies performed each year, because an anesthesiologist or nurse anesthetist has to be paid, too.

And more and more people are getting anesthesia with that colonoscopy. In 2003, just 14 percent of people had an anesthesiologist or nurse anestheticist, according to the study in JAMA, the Journal of the American Medical Association.

By 2009, that number had risen to 30 percent. Most of that increase was for healthy people who don’t have a condition that would require anesthesia.

People in the Northeast are much more likely to get anesthesia services. That happened 59 percent of the time, compared to 13 percent in Western states, where insurers have balked at paying the extra cost, saying that almost all people do just fine with sedatives administered by the doctor doing the endoscopy.

“The financial incentives are a little perverse,” says Lee Fleisher, chair of the department of anesthesiology and critical care at the University of Pennsylvania Health System.

This isn’t a new issue. In recent years insurers have been trying to back off on paying for anesthesia with propofol, a fast-acting drug that usually requires the services of an anesthesiologist or a nurse anesthetist.

Here’s why.

Gastroenterologists get paid just as much if an anesthesiologist is involved, but since they don’t have to manage sedation, they can work more quickly and handle more cases in a day, Fleisher says. They also avoid potential liabilty for patients who might react badly to sedatives. But insurers end up paying for more personnel, and the anesthetic.

“We’re covering it,” says Scot Roskelley, a spokesman for Aetna. The insurer had said it would stop paying for anesthesia back in 2008, but has decided to delay that change indefnitely, Roskelley told Shots.

The cost ranges from $150 for people insured by Medicare to $508 for people covered by a private insurer.

So in some endoscopy centers, patients are given full anesthesia as a matter of course, even though most healthy patients don’t need that much sedation, or that level of monitoring. Medicare covers the costs, as do some private insurers.

“The finances have made it easy not to make a difficult decision,” Fleisher told Shots. He wrote an editorial in this week’s JAMA.

His hospital routinely uses moderate sedation, also called “twilight sleep” with sedatives like Valium or Versed. Most people don’t remember the procedure, and experience little or no discomfort. (Some people have colonoscopies and other medical procedures with no sedation at all, but that’s a story for another day.)

So there’s a case to be made for insisting that healthy people use moderate sedation rather than being put to sleep by an anesthesiologist, Fleisher says. But there’s also a risk that people who are leery of the discomfort of colonoscopy would skip the procedure, increasing their risk of colon cancer.

“If we say tomorrow that anyone who is healthy is denied anesthesia, my fear is that people will stop getting their colonoscopies,” Fleisher says.

In the end, he says, it makes sense that people who do want to have full anesthesia pay a bit more for the service. “If it makes a difference, I’d be willing to pay for that difference. The real question is figuring out a way so that people are using the resources the most rational way.”

Sleep vs Coma vs Anesthesia

Sleep Versus Coma

The word Coma derives from the ancient Greek word for sleep, but as applied in modern medical terminology, coma refers to another state altogether. The comatose person lies unmoving, except for shallow breathing, indefinitely. People can be in comas for a few hours up to years. They appear dead to the outside world, except upon close inspection.

Comas are usually caused by brain injuries or other severe trauma. They are largely a mystery and people can emerge from comas at times unforeseen by doctors. Healing can occur during a coma, but it appears to be a slow process. People in a coma do not demonstrate external signs of sleep. They do not move (as people in NREM sleep do), and their EEG readings are inconsistent with sleep. The person cannot be woken up, even with powerful stimuli. Doctors use the Glasgow Coma Scale in their assessment of coma patients. (An alternative is the Rancho Los Amigos Scale..)

In extreme medical situations, doctors use chemicals to induce coma in patients as part of a treatment strategy. Sometimes coma patients can actually hear and remember things people say to them when they are in the coma. Medical intervention is required to maintain life if the coma persists for days; patients are given nutrition intravenously.

The term vegetative state refers to something else. The person in a vegetative state is not in a coma. Also called a “coma vigil” or Apallic Syndrome, this state poses ethical dilemmas because patients do not recover. Their brainstem continues to function, and with artificial hydration and nutrition they can live indefinitely. They may even open their eyes and they show a sleep cycle (albeit not a normal one). But the higher order brain functions are gone. They do not respond to stimuli and cannot be aroused. There is an effort to rename this state Unresponsive Wakefulness Syndrome.

Anesthesia

Anesthesia reduces the sensation of pain produces temporary amnesia, and stops movement of the skeletal muscles. The only stage of sleep where skeletal muscles are paralyzed is REM, but brain activity differs substantially between REM and anesthesia.

General anesthesia is when the person is made unconscious. It is so common that 60,000 surgical patients go under every weekday just in the United States. The person under anesthesia does not respond – even the deepest sleep is not as deep (measured by response to stimuli) as anesthesia.

Colloquially this is called “going to sleep”, but it is strictly speaking not a form of sleep. The doctor may even tell the patient and his or her family that the surgery will occur while the patient is asleep, but this is a simplification and the doctor knows it. In a way, general anesthesia is a reversible coma. EEG readings of brain activity are not similar to those of any stage of sleep. Indeed, readings are closer to those of a comatose patient.

Physiologists have created a measure called the bispectral index to measure the depth of sedation and anesthesia. It indicates coherence among different frequencies measured in nervous system rhythms. The scale runs from 0 to 100, and a high number reflects good cortical integration that occurs during waking. The deeper the anesthesia state, the lower the bispectral index number. In medical anesthesia uses, the index is typically 40 to 45.

Of course anesthesia is not normal sleep and when under anesthesia the person does not experience REM. This is true for most anesthesia drugs used in medical procedures. Subjects accumulate a “REM debt” when under anesthesia and experience rebound REM in the day following. This suggests that there is a REM homeostat the same way there is an overall sleep homeostat (process C in the two-process theory). Some drugs (e.g. isoflurane and sevoflurane ) allow the brain to get its needed NREM sleep, but the anesthesia drug halothane does not. The drug propofol is an exception to the anesthesia rule, as people do not seem to accumulate an REM debt while under its effects, and indeed, sleep debt present upon going under propofol disappear while the anesthesia is in effect.

They make a big deal about risk in hospitals when it comes to anesthesia. The large majority of patients weather it, but the reduced heart rate and blood pressure and general metabolism increase the chances of death. About one in a thousand patients wakes up during anesthesia, leading to sometimes psychologically horrifying consequences. More scary is when patients do not wake up from anesthesia on schedule. Some with neurological conditions spend hours unconscious before waking while the doctors worry. Narcoleptics can take 8 hours to wake up, while a healthy person takes a few minutes. Animal experiments suggest that the orexin deficiency associated with narcolepsy affects waking from anesthesia, not going under.

Even in healthy people, there is an inertia – analogous to sleep inertia perhaps. Levels of the anesthesia drug must fall to a lower level for the patient to awaken that it takes to put him or her to sleep.

Attribute Sleep Coma Anesthesia
Will last less than 12 hours Yes No Yes
Can be induced by drugs Yes Yes (in rare medical procedure) Yes
Person can feel pain Yes No No
Inertia upon awakening Under 1 hour Days or weeks Up to a day
Person awakens in response to sounds or shaking Yes No No
Experienced as refreshing Yes No Not usually
Indicates neurological damage No (except some hypersomnia) Yes No

Surprisingly, doctors have been able to awaken some coma patients by giving them zolpidem. The mechanism for this phenomenon is not known. Another mystery of the brain and consciousness.

PMC

Dr Rakesh Bhandari is an Assistant Professor in the Department of Anesthesia and Perioperative Medicine at the University of Western Ontario, London, of the operating room, he has an interest in the Management of Anesthetic Care, and has direct experience in the use of propofol during endoscopic retrograde cholangiopancreatography.

“The Propofol wave which seemed at one point to be about to break over the USA like a tsunami has yet to reach the shore” (1).

PA: It has been reported that 17% of gastroenterology (GI) units in the United States use propofol for endoscopy and 43% of units considered its use in 2005 (1). The advantages of this approach may include rapid induction and recovery, and improved patient and physician comfort. However, these benefits come at a cost and many GI units in Canada are satisfied with their current use of benzodiazepines and narcotics. Can you review the characteristics of propofol?

Dr Rakesh Bhandari is an Assistant Professor in the Department of Anesthesia and Perioperative Medicine at the University of Western Ontario, London, Ontario

RB: Propofol is an isopropylphenol that is administered intravenously as 1% solution for the induction of anesthesia or as an intravenous sedation agent. It was introduced in the mid 1980s and has been used for hundreds of millions of procedures worldwide. Propofol is presumed to exert its effect through its interaction with gammaaminobutyric acid receptors, the principal inhibitory neuro-transmitters in the brain. When administered intravenously, propofol is rapidly cleared from the circulation. Its clearance takes place by redistribution possibly into the lungs and more importantly in the liver. Only 0.3% of the dose is excreted, unchanged, in the urine. The elimination half-life of propofol is approximately 0.5 h to 1.5 h. This drug has a very fast clearance and therefore can be administered as a continuous infusion or as multiple boluses without any accumulative effects. Propofol has been used as the drug of choice for the induction of anesthesia and also for intravenous conscious sedation.

In healthy adults, the general anesthesia intravenous induction or deep sedation doses of propofol is 1.5 mg/kg to 2.5 mg/kg, which should be decreased in elderly or debilitated patients by up to 50%. Consciousness returns within 10 min to 15 min after administration of these doses have been discontinued, and provided no or very small doses of coadjuncts such as fentanyl, midazolam, etc, are used.

Quick recovery without much residual sedation, and low incidence of nausea and vomiting, make propofol the drug of choice for conscious sedation in ambulatory anesthesia. Generally, a continuous infusion intravenous dose of propofol (25 μg/kg/min to 100 μg/kg/min) is used to induce amnesia and light sedation. Patients usually recover within 5 min to 10 min after discontinuation of this infusion. If a clinician chooses to use adjunct medications such as midazolam and fentanyl, this recovery phase may be prolonged. Along with this sedative hypnotic effect, propofol provides some antiemetic and antipruritic effects. It has no analgesic properties.

The most common side effect of propofol is peripheral vasodilation resulting in hypotension. Peripheral vasodilation is primarily due to a decrease in the sympathetic outflow from the central nervous system. There may be some negative inotropic effects of propofol from the decrease in intracellular calcium availability. There is a risk of bradycardia-related death during propofol administration which has been reported to be 1.4 in 100,000 patients. Propofol also produces dose-dependent depression of ventilation and causes apnea in approximately 25% to 35% of patients. Other coinduction drugs and narcotics, such as midazolam and fentanyl, may enhance this ventilatory depression. Other minor side effects include pain on injection that can be decreased by concurrent or pre-emptive use of intravenous xylocaine. Propofol also promotes bacterial growth; therefore, it cannot be kept for more than 4 h after opening the drug. There are no known reversal agents available for propofol.

PA: Can you comment on bolus and infusions of propofol? How soon does a patient recover? Are they able to drive home?

RB: For short procedures, like upper and lower GI endoscopy, an infusion of propofol ranging from 25 μg/kg/min to 100 μg/kg/min could be used, resulting in a cooperative patient with amnesia for endoscopy. This provides awakening and orientation within 5 min to 10 min after discontinuation of the infusion. Propofol can be used as a single large bolus followed by multiple small boluses depending on the duration of the procedure. A typical dose used for this technique would be 0.5 mg/kg to 1 mg/kg body weight followed by small doses of 10 mg to 20 mg intravenous propofol. For brief procedures just lasting 5 min to 10 min, I personally prefer to give a bolus followed by small doses as required. It is not advisable for the patient to drive home after propofol administration.

PA: Is it possible to have pain while unconscious from propofol?

RB: Yes, it is possible to have pain while the patient is unconscious from propofol because it provides no analgesia.

PA: Who should administer propofol in the endoscopy room? In the United States and other countries, there seems to be a model developing for specialized nurses to administer propofol (2,3).

RB: As quoted from the product insert for propofol (Diprivan, AstraZeneca Canada Inc):

“For general anesthesia or monitored anesthesia care or sedation propofol injectable emulsion should be administered only by persons trained in the administration of general anesthesia and not involved in the conduct of the surgical/diagnostic procedure.”

The American College of Gastroenterology has petitioned the Food and Drug Administration to change the package insert for propofol to allow its use by people not trained in airway management. In Canada, we have no certified registered nurse anesthetists (CRNAs) to provide administration of propofol in the endoscopy room. The Canadian Anesthesiologists’ Society (CAS) formed a task force on anesthesia assistants in 1995. The CAS guidelines (4) stated that:

  • An anesthesia assistant would usually be a respiratory technologist because they have airway management skills and training in the use of drugs;

  • They will work under the direct supervision of an anesthesiologist; and

  • Their role is supportive and does not involve independent practice.

After 15 years, this is still a work in progress, and a big question is who will pay for these positions. The task force concluded that anesthesiologists would retain the responsibility for patient care and that the anesthesiologist and anesthesia assistant would work as a team to provide the best care. The task force also determined that there is a place for assistants in the delivery of anesthesia services due to the expanding nature of anesthesia services inside and outside the operating room. The CAS also sees no role for the independent practice of anesthesia by CRNAs. Currently, there is no system for training of CRNAs in Canada. Also, I would like to say that if there is a serious shortage of nursing personnel in other areas of nursing care, how can we expect registered nurses to take on more responsibility in different areas of medical practice? From my personal experience, I think using the CRNA model may not be cost-effective because one anesthesiologist performs the workload of approximately 2.5 to three CRNAs. This seems to be more of a political issue than an actual patient care issue. I also hear there is talk of using nurse practitioners for performing endoscopies because there is a backlog of patients who need upper and lower GI procedures. Personally, as a patient, I would not like to have a nongastroenterologist performing an endoscopy and making very important decisions affecting my life.

PA: There seems to be a shortage of anesthesiologists in Canada. Is it likely that we could find an MD anesthesiologist who would choose to work full time in an ambulatory GI unit? What is the anesthesiology fee for an endoscopic procedure in Canada?

RB: There does seem to be a shortage of anesthesiologists in Canada. As I have already mentioned, for the past 15 years, the CAS has been involved in developing and implementing guidelines for anesthesia assistants because they anticipated a shortage of anesthesiologists due to the lack of insight in government policies. In my opinion, this anesthesia assistant model could be used to provide intravenous sedation for GI endoscopies. There may be some anesthesiologists who are interested in providing anesthesia care for endoscopies. The current Ontario Health Insurance Plan fee for anesthesia care of endoscopic procedures is approximately $100.

PA: Enthusiasts hope that propofol will greatly increase throughput because of its short recovery time. This is offset by the costs of anesthesia care. There may also be enhanced patient safety with this approach. How do you see the balance of benefits of costs in a Canadian health care environment?

RB: The answer to this question is yes and no, which depends on your current practice. If you require a longer period of time to get the patient adequately comfortable for the procedure, then I think propofol administration by trained personnel may decrease the amount of time required to reach the level where the patient is comfortable. Although there may not be any cost savings involved, there may be a higher degree of patient and endoscopist comfort level. I also think that the time may come when patients would be willing to pay from their own pocket for this procedure to be comfortable.

Propofol

Generic Name: Propofol (PROE po fole)
Brand Name: Diprivan, Fresenius Propoven

Medically reviewed by Drugs.com. Last updated on Jul 26, 2019.

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Uses of Propofol:

  • It is used to put you to sleep for surgery.
  • It is used to calm you before a procedure.
  • It is used to cause sleep during a procedure.
  • It may be given to you for other reasons. Talk with the doctor.

What do I need to tell my doctor BEFORE I take Propofol?

  • If you have an allergy to propofol, eggs, soy products, or any other part of propofol.
  • If you are allergic to any drugs like this one, any other drugs, foods, or other substances. Tell your doctor about the allergy and what signs you had, like rash; hives; itching; shortness of breath; wheezing; cough; swelling of face, lips, tongue, or throat; or any other signs.
  • If you are breast-feeding. Do not breast-feed while you take propofol.

This medicine may interact with other drugs or health problems.

Tell your doctor and pharmacist about all of your drugs (prescription or OTC, natural products, vitamins) and health problems. You must check to make sure that it is safe for you to take propofol with all of your drugs and health problems. Do not start, stop, or change the dose of any drug without checking with your doctor.

What are some things I need to know or do while I take Propofol?

  • Tell all of your health care providers that you take propofol. This includes your doctors, nurses, pharmacists, and dentists.
  • Very bad and sometimes deadly allergic reactions have rarely happened. Talk with your doctor.
  • Avoid driving and doing other tasks or actions that call for you to be alert until the effects of propofol wear off and you feel fully awake.
  • Talk with your doctor before you drink alcohol or use other drugs and natural products that slow your actions.
  • Talk with your doctor if you have seizures or have ever had seizures.
  • High triglyceride levels have happened with propofol. Tell your doctor if you have ever had high triglyceride levels.
  • If you are 65 or older, use propofol with care. You could have more side effects.
  • Studies in young animals and children have shown that frequent or long-term use of anesthesia drugs or drugs used for sleep in children younger than 3 years of age may lead to long-term brain problems. This may also happen in unborn babies if the mother uses propofol during the third trimester of pregnancy. Talk with the doctor.
  • Use with care in children. Talk with the doctor.
  • Some products have benzyl alcohol. Do not give a product that has benzyl alcohol in it to a newborn or infant. Talk with the doctor to see if this product has benzyl alcohol in it.
  • Tell your doctor if you are pregnant or plan on getting pregnant. You will need to talk about the benefits and risks of using propofol while you are pregnant.

How is this medicine (Propofol) best taken?

Use propofol as ordered by your doctor. Read all information given to you. Follow all instructions closely.

  • This medicine is given as a shot into a vein or into a vein nonstop for a period of time.

What do I do if I miss a dose?

  • This medicine will be given on an as needed basis in a healthcare setting.

What are some side effects that I need to call my doctor about right away?

WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:

  • Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing, swallowing, or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.
  • Signs of a pancreas problem (pancreatitis) like very bad stomach pain, very bad back pain, or very bad upset stomach or throwing up.
  • Signs of high or low blood pressure like very bad headache or dizziness, passing out, or change in eyesight.
  • Trouble breathing, slow breathing, or shallow breathing.
  • Slow heartbeat.
  • Trouble controlling body movements, twitching, change in balance, trouble swallowing or speaking.
  • This medicine may rarely cause a severe health problem called propofol infusion syndrome (PRIS). Sometimes, this has been deadly. The chance of PRIS may be higher with high doses of propofol or with long-term use. Tell your doctor right away if you feel confused, very sleepy, or very tired or weak. Tell your doctor right away if you have dark urine or are not able to pass urine; fast breathing; a fast or abnormal heartbeat; muscle pain or weakness; severe stomach pain, upset stomach, or throwing up; or shortness of breath, a big weight gain, or swelling in the arms or legs.
  • This medicine may cause tissue damage if the drug leaks from the vein. Tell your nurse if you have any redness, burning, pain, swelling, blisters, skin sores, or leaking of fluid where the drug is going into your body.

What are some other side effects of Propofol?

All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:

  • Feeling sleepy.

These are not all of the side effects that may occur. If you have questions about side effects, call your doctor. Call your doctor for medical advice about side effects.

You may report side effects to the FDA at 1-800-FDA-1088. You may also report side effects at http://www.fda.gov/medwatch.

If OVERDOSE is suspected:

If you think there has been an overdose, call your poison control center or get medical care right away. Be ready to tell or show what was taken, how much, and when it happened.

How do I store and/or throw out Propofol?

  • If you need to store propofol at home, talk with your doctor, nurse, or pharmacist about how to store it.

Consumer information use

  • If your symptoms or health problems do not get better or if they become worse, call your doctor.
  • Do not share your drugs with others and do not take anyone else’s drugs.
  • Keep a list of all your drugs (prescription, natural products, vitamins, OTC) with you. Give this list to your doctor.
  • Talk with the doctor before starting any new drug, including prescription or OTC, natural products, or vitamins.
  • Keep all drugs in a safe place. Keep all drugs out of the reach of children and pets.
  • Throw away unused or expired drugs. Do not flush down a toilet or pour down a drain unless you are told to do so. Check with your pharmacist if you have questions about the best way to throw out drugs. There may be drug take-back programs in your area.
  • Some drugs may have another patient information leaflet. Check with your pharmacist. If you have any questions about propofol, please talk with your doctor, nurse, pharmacist, or other health care provider.
  • If you think there has been an overdose, call your poison control center or get medical care right away. Be ready to tell or show what was taken, how much, and when it happened.

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.

Medical Disclaimer

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  • Propofol

Other brands: Diprivan, Propoven

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Related treatment guides

  • Anesthesia

Using Propofol for Difficult-to-Treat Headaches in the ED

Sergey M. Motov, MD: Before we start, I want to thank Rick for pushing the agenda and putting together these amazing publications. Thank you for doing this.

At present, I think propofol is not ready for prime-time, first-line treatment, but we should definitely consider using it. In my practice, I resort to propofol when traditional treatment modalities, as you mentioned—the neuroleptic cocktail, nonsteroidal anti-inflammatory drugs—fail to achieve appropriate analgesia after two or three doses. I resort to propofol as a rescue analgesia.

Deciding on Which Patients to Treat With Propofol

Dr Glatter: Do you find it to be appropriate for certain kinds of patients?

Dr Pescatore: That is a great question. I would flip that around a bit. There is certainly a cohort of patients for whom the neuroleptic agent has a bit of a necessary secondary effect. There also is a patient population for whom propofol is more effective. We have yet to parse out that patient population.

I have had a lot of success with propofol in patients with complex migraines, specifically patients with ocular migraines who are temporarily blinded by the severity of their headaches. It is amazing to watch them regain their sight after a low dose of propofol. I do not yet know who the population is that benefits from this. For now, I use a taste-test approach.

Reserving for rescue analgesia is certainly a reasonable and laudable way to use this. As we gain greater clinical experience with propofol, as we are more comfortable with it, and as we begin to identify patient populations for whom it is particularly effective, I do see it becoming more of a first-line agent.

Dr Glatter: Sergey, what are your thoughts on this?

Dr Motov: Obviously, those with resistant headache would be a subgroup of patients who would be eligible for this type of analgesia, and my favorite group of patients, pregnant women in their third trimester. Let’s look at this while considering the US Food and Drug Administration’s ABCD classifications of drugs for pregnant women.

I saw a patient recently, a 35-year-old pregnant patient who came to me with intractable headache. It was not a gestational headache. It was just a headache, a migraine headache. She did not have preeclampsia. She had gotten metoclopramide, which is a category B drug—no risks have been found in humans. She got magnesium, which was classified as a B drug but now is a D—indicating the potential for adverse events in humans. Then she got a second dose of metoclopramide, but nothing worked.

If I go by the classification categories, propofol is in category B. The patient comes to me from labor and delivery because of intractable headache. I used 10 mg of propofol every 5 minutes; I broke her headache at 60 mg. She was absolutely the happiest woman alive. She was headache-free, and she went home. For pregnant women in the third trimester, propofol is safe. Use it.

Dr Glatter: I can imagine the pushback from other providers just thinking about pregnancy, and especially the obstetrician in how they would approach this. Certainly, with its categorization, I believe it is safe. I guess the issue is monitoring the patient.

Hospital Administration of Propofol

Dr Glatter: A lot of nurses and administrators are concerned about the problems this drug has had in the past. Here we are trying to push propofol in small aliquots. How do we approach the hospital administration? What is the best plan?

Dr Pescatore: That is the key question that comes up when we talk about using propofol for headache. The first thing to get across here is that it is not the drug that causes sedation. It is the dosage and the intent behind giving the drug. As Sergey said, the small doses we’re administering are incredibly similar in effect to low-dose or subdissociative ketamine use.

There is no need to use standard conscious sedation or moderate sedation protocols when we administer propofol in the manner we are discussing. Are we going to be reckless with it? Absolutely not, and certainly we will take into account the fact that this drug has a history associated with it.

There is no emergency physician alive who is not comfortable with this drug, who does not understand how to use it. We will monitor the patient for respiratory depression as we would for any opioid analgesic, for example. But this is an incredibly safe drug.

Dr Glatter: Do you have a specific, written protocol at your hospital that you refer to?

Dr Pescatore: I have been lucky enough to work at quite a few hospitals. One or two of these hospitals required a written protocol, but the vast majority of my use of this drug is similar to my use of any other drug in the ED.

Dr Motov: I agree with Rick and with you, Robert. In our traditional thinking, the doctor and nurse are the champions of the patients, and everything fits into the place. But I would bring a bit of caution: I believe to protect ED personnel, you have to protocolize it.

You have to clearly say that this is a subanesthetic dose of propofol. It does not require monitoring. Propofol does not require any interventions beyond the usual, similar to what we do with morphine. I believe it needs to be protocolized and vetted by the department of nursing, other department chairs, and everyone else. I would push for getting it protocolized and then roll it out.

Propofol Over Ketamine: What Are the Advantages?

Dr Glatter: Why not use low-dose ketamine rather than propofol? What is the advantage or disadvantage?

Dr Pescatore: I would defer to Sergey for this. He is clearly the expert. But propofol may add something that ketamine lacks; you get a bit of GABA action from propofol. There is a bit of inhibition of cortical spreading depression that you won’t get from the ketamine. That is not to say that ketamine can’t be effective. This is just another tool to place in our toolbox, and it adds to that versatility.

Dr Glatter: What will make you select propofol over ketamine when you look at a given patient? Can you point to anything specific?

Dr Pescatore: I can’t say that there is anything I have been able to parse out. I believe we all have had enough experience with ketamine now that we can look at a patient and say this is probably not the best patient for ketamine.

Dr Glatter: If the patient has a psychiatric history and a history of agitation, is that something you will consider when you’re looking at ketamine versus propofol?

Dr Pescatore: Without question, that goes into it. I also look at the blood pressure. Patients who are profoundly hypertensive may be more amenable to propofol than ketamine, for example. Then overall, I look at the severity of their symptoms.

Dr Motov: I have been using a stepwise approach to just about all headaches. If propofol fails, I resort to ketamine. I resort to ketamine to double the NMDA blockade. I use ketamine if propofol fails, and as Rick said, in the patients with schizophrenia or excessive weight, and perhaps pregnant women, I avoid ketamine because it is not entirely safe. I am also not going to give it to young children.

Ketamine is essentially a very safe medication. The hemodynamic compromise, which happens with certain doses of ketamine, is negligible. But I start with propofol. If propofol fails, at least I have something else to rely on and use before I go to general anesthesia and total sleep.

Treating Pediatric Migraine in the ED

Dr Glatter: What about pediatric migraine? Have either of you used this approach in that population?

Dr Pescatore: I have, absolutely. In fact, I find propofol to be particularly effective in the pediatric population. One of the studies that planted the seed in my mind was in a pediatric population. Propofol is even safer in this population than in patients who have any possibility of respiratory compromise, and it is very effective.

Dr Motov: I have not used it in pediatric patients because I primarily see adults. But I agree with Rick. One of the first trials that evaluated a subanesthetic dose of propofol used it in pediatric patients.

Propofol Versus Subcutaneous Sumatriptan

Dr Glatter: I want to talk about a randomized 2014 trial that compared subcutaneous sumatriptan versus intravenous propofol. The study found no significant difference at 1 and 2 hours, although there was more improvement in the propofol group at 30 minutes.

Propofol reduced the side effects that you often would see with sumatriptan—the nausea, the vomiting, maybe some chest pain, things of that nature. What are your thoughts on this trial?

Dr Pescatore: I believe the side effects, in the administration of all these drugs, are truly the crux of this issue. They are all going to be effective. If we are couching that in a setting of a whole bunch of side effects and a whole bunch of prolonged ED stays, whatever we can do to minimize that is a target for me.

Dr Motov: I always have an issue when a titratable medication is compared with a nontitratable medication. Also, the route of administration is different. Remember, sumatriptan has a fairly narrow indication, for migraine headache only. In contrast to that, propofol can be used for any type of headache, as long as the headache is multidrug-resistant. Side effects are side effects. I personally believe that propofol is safer than sumatriptan. If it is a young patient with a complicated migraine and propofol helps, go ahead and use it.

Final Thoughts on Propofol

Dr Glatter: Rick, you brought up the length of stay in the ED, and that is a key issue. Earlier, we were saying that 15-20 minutes could be the total duration of the ED stay, with pain relief and subsequent discharge. But do you have to monitor these patients for any significant time afterward?

Dr Pescatore: Absolutely not. There is no reason to continue observing these patients after they have endorsed that the propofol’s effects are gone. Propofol has an incredibly short half-life. Patients’ headaches are relieved almost immediately. Then they get a Tylenol®, and they go out the door. In my experience, it is a rapid discharge. There is a very low rate of headache recurrence, it is incredibly successful, and it leaves the bed empty for the next patient with a headache.

Dr Glatter: Are you finding the same, Sergey? A very quick discharge after you administer propofol?

Dr Motov: Yes. I completely agree with Rick.

Dr Glatter: Why shouldn’t we be using this drug for headache throughout the United States? What are the issues that prevent this from being adopted?

Dr Pescatore: The biggest issue is the stigma. People are afraid to administer this medication because of the Michael Jackson stigma and the stigma of conscious sedation. I believe we will get there; I really do.

Dr Motov: I agree 100%. People need to understand that we are not sedating patients; we are just taking care of their pain.

Dr Glatter: Is there any risk for physical or psychological addiction? Will people be returning to the ED to get a euphoric effect?

Dr Pescatore: I would love to hear what Sergey has to say about this. I am not aware of any literature that has looked at the addiction potential or dependence level of propofol. In my own experience, I have not seen that happen. Contrary to the warnings of my colleagues that patients will be bouncing back for their fix, I have not seen that.

Dr Motov: I have yet to see a patient come back to the ED and ask for propofol.

Dr Glatter: I believe we need a larger, randomized study to really flesh out and validate the results of these smaller trials. Do either of you have any other ideas you wanted to bring up or thoughts about propofol?

Dr Pescatore: My parting message is that we do many things in the ED that have little, if any, knowledge base surrounding them. If there is a drug that emergency physicians are more than comfortable with, it is propofol. If there is a drug with as wide a therapeutic window as propofol, I would like to see it. Propofol is incredibly effective, with a rapid onset of effectiveness, and with only limited danger associated with it. I believe it offers a good option for many of our patients.

Dr Motov: I agree. I will just add this: The key to the success of using propofol for headaches is to use it for properly selected patients at a properly selected dose, understanding that we are not sedating patients but taking care of pain by using a protocolized approach that is vetted by nurses and doctors in the ED.

Dr Glatter: I believe that brings home the message. We are trying to spare opioids. We are trying to help patients. This is a valid approach that has been validated by research and is something we can reach into our toolbox and use.

Thank you both. This has been a very informative discussion.

IV Propofol for Treatment of Chronic Intractable Cluster Headache: A Case Series

The headaches had progressed to a daily intractable cluster-like headache disorder over the course of 7 months. I opted to use IV propofol in the clinic at 50 mg in 1 to 2 doses, which markedly reduced her nausea. After increasing the propofol dose to 80 mg per dose, 6 to 8 doses nearly eradicated the headache.

Three to 4 days of such treatment allowed the CH episode to abate, leaving her with her usual migraine and CRPS pain pattern, though both were markedly reduced as well. Her anxiety and depression scores were lowered by more than half, and her mood improved greatly. Neck, back, and hip pain were also much easier to manage with less pain medication. I also prescribed ketamine in a timed-release base, 75 mg per dose, 3 times a day, because she lives more than 3 hours from the clinic. She has not had any more CH flare-ups thus far.

Summary

The dedicated use of IV pharmacological agents with differing but often complementary and even synergistic effects may result in reductions in chronic pain and headache patterns. Not everything works for everyone, and multiple infusion trials with dosage adjustments are often needed to gain the benefits of IV therapy.

The cases presented are anecdotal, but they represent the extreme end of the spectrum of a rare and very disabling TAC, such as CH. In my experience, one-time IV treatment and rapid infusions do not offer long-term benefits to the patient. Patients who were treated more aggressively, repeatedly, or for longer periods of time may benefit from this approach.

Therefore, alternative delivery systems that are more self-directed may represent a novel change in effective treatment. Aggressive oral inhalational treatment is an alternative method that may maintain the response to IV propofol treatment, at least in theory. Therefore, it is most desirable to find a route of administration for propofol that not only has the potential to reduce or eliminate the CH episode, but also has the convenience of a self-administered dosing system.

Reduction and/or removal of opioids is always a goal, particularly in chronic daily headache and neuropathic pain syndromes. Ketamine, low-dose naltrexone, human chorionic gonadotropin (hCG), and other approaches like low-dose buprenorphine or use of neuronal stabilizing agents may also be useful in reducing opiate usage. Ketamine, if successful via IV, can be considered in other delivery systems. Likewise, lidocaine offers the possibility of trying many neuronal stabilizing oral agents that block sodium channels. IV lidocaine, by itself, indiscriminately blocks many, if not most, sodium channels, while different oral agents are more limited in their pharmacological blockade.

Thus, insoluble medications, such as propofol, which currently must be given via IV, may be considered for novel delivery systems or devices for administration. This would represent a large step forward in the rapid, at-home treatment of severe, debilitating CH and other rare pain syndromes that arise at night or very quickly. The increased costs and inconvenience of IV propofol in an outpatient setting, both to the patient and the clinician and staff, are limiting factors in this treatment scenario.

Self-administration by the patient, with appropriate safeguards, may represent a new and efficacious degree of treatment for this and other rare disabling disorders, such as hemicrania continua, paroxysmal hemicrania, trigeminal neuralgia, CRPS, vulvodynia, pudendal nerve entrapment, atypical face pain syndromes, and other rare and highly disabling syndromes.

View Sources

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  2. Krusz JC. Aggressive interventional treatment of intractable headaches in the clinic. Clin Fam Pract. 2005;7:545-565.
  3. Krusz JC, Belanger J. Cost Effectiveness of Clinic Treatment of Headaches and Pain. Oral presentation at: The 8th World Congress, The Pain Clinic; May 1998; Tenerife, Canary Islands.
  4. Krusz JC, Scott V, Belanger J. IV propofol—a uniquely effective agent for the treatment of acute headaches. Poster presented at: American Association for the Study of Headache, Annual Meeting. Boston, MA. June 1999.
  5. Krusz JC, Scott V, Belanger J. Propofol—a highly effective treatment for acute headaches. Cephalalgia. 1999;19:358.
  6. Krusz JC, Scott V, Belanger J. Effectiveness of intravenous propofol in treating refractory migraine headaches. Poster presented at: American Pain Society Annual Meeting; October 1999; Ft. Lauderdale, FL.

Last updated on: June 15, 2017 Continue Reading: Schizophrenia Spectrum and Chronic Pain: Is Pain Insensitivity a Myth?

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