FESS surgery and TIVA

 About a two years ago an ENT surgeon I have never worked with requested that I use a TIVA for her patient who was having an endoscopic sinus surgery.   I thought this an odd request.  I did an initial literature search and indeed found a few studies supporting this concept.  However, there were other studies that were not able to replicate this finding.  Also, it was noted that remifentanil was alway included in the studies where TIVA was found to improve the visibility in the surgical field. Therefore, I came away from this review not fully convinced that propofol infusions could make a clinically relevant difference in the ability of the surgeon to see during sinus surgery.  Furthermore, I could think of no biologic plausibility for this effect.  

Today, I was completing my mandatory MOCA questions in the app that is provided. One of the questions asked what is the best choice of anesthesia to improve the visibility of the sugical field during endoscopic sinus surgery.  The correct answer was a TIVA with remifentanil.  This prompted me to once again do a literature reveiw to update my knowledge in this regard.

The main support for the idea that TIVA is ‘better’ than inhalational comes from a meta-analysis of over 500 [1] patients having endoscopic sinus surgery.  In this meta analysis, the TIVA group, had better surgical field visibility.  However, the real headline from the meta-analysis was probably that when you dive in, it appears that the benefit of TIVA is lost if you trade in fentanyl for remifentanil [2].  There is an RCT that does not support the findings of the meta analysis however [3]. This group had three arms, Desflurane only, Desflurane + remi,  propofol + remi and found difference in FESS.  It is important to note in this RCT, the MAP was carefully held at between 65 - 70 mmHg. Of note, in the propofol group, significantly larger remifentanil dosages were used to accomplish the same anesthetic end target.  If remifentanil is important in improving the surgical field, then this may indicate why propofol in other studies might seem to produce better results when compared to inhalalational anesthetics.  

Importantly, in this same literature search, I was able to identify several studies showing a benefit of lidocaine in improving surgical field visibility.  In a 2024 systematic review, lidocaine was found to improve the surgical field in FESS surgery.  In a RCT in 2022 [4], 1.5 mg/kg of lidocaine was given up front followed by a 1.5 mg/kg/hr infusion.  This resulted in significantly reduced blood loss and improved surgical field visibility.  

Other studies have also shown that controlled hypotension with either propofol or esmolol can reduce intraoperative blood loss in endoscopic sinus surgery and leads one to believe that the real culprit for the results seen in the above studies is more likely related to reduced sympathetic tone and blood pressure in the group that saw improved results.  

Guven et al. [5] were able to show that dexmedetomidine was slightly better than remifentanil in improving the surgical field during FESS.  Another group [6] in a RCT were able to demonstrated that adding an infusion of dexmedetomidine to a background anesthetic of propofol/remifentanil reduced blood loss and improved the visibility of the surgical field. Finally, in 2024, Warner et al. published a meta analysis [7] of 31 RCT with 935 patients.  They were able to show that dexmedetomidine resulted in better surgical field visibility and reduced blood loss compared to placebo and compared to propofol. 

Unfortonuately, our surgical colleagues, or more specifically, the ENT surgeons who may now request TIVA with propofol to improve visualization during endoscopic surgery may not be so nuanced.  Therefore, it is likely that we are going to be mandated in some cases to either spend effort attempting to explain the nuances of the studies, or simply add some propofol to our FESS anesthetics.  Our friendly surgical colleagues will unfortunately be unaware that the most optimal surgical field visibility is likely going to result from optimal control of sympathetic outflow during surgery (i.e. avoiding elevated BP and HR).  Currently, the evidence seems to suggest that using agents that lower blood pressure by inhibiting surges in sympathetic output can improve the surgical conditions during endoscopic sinus surgery.  Given this information, I would opt for a propofol infusion if I was wanting to prevent PONV, but not if it was only for the improvement of the surgical field.  It seems reasonable to add boluses of lidocaine in a dose that approximates 1.5 mg/kg iv bolus up front followed by doses that accumulate to 1.5 mg/kg/hr for the duration of the case.  Additionally, I would strongly consider adding dexemedotimine given the evidence cited above.  Furthermore, it is easier to use than remifentanil, tends to provide smoother emergence and has been linked to reduced post op delirium in the elderly and is very good at reducing emergence delerium in the younger ones.

1. Boezaart AP, Tighe PJ, Laur JJ, Yegiaian C, Bevensee AM.

Anesthesia Type and Surgical Field Visibility During Endoscopic Sinus Surgery: A Systematic Review and Meta-analysis.

JAMA Otolaryngol Head Neck Surg. 2021;147(1):23–32.

2. Kolia NR, Man LX. Total intravenous anaesthesia versus inhaled anaesthesia for endoscopic sinus surgery: a meta-analysis of randomized controlled trials. Rhinology. 2019 Dec 1;57(6):402-410. doi: 10.4193/Rhin19.171. PMID: 31329812.

3. Gollapudy S, Gashkoff DA, Poetker DM, Loehrl TA, Riess ML. Surgical Field Visualization during Functional Endoscopic Sinus Surgery: Comparison of Propofol- vs Desflurane-Based Anesthesia. Otolaryngol Head Neck Surg. 2020 Oct;163(4):835-842. doi: 10.1177/0194599820921863. Epub 2020 May 26. PMID: 32450733; PMCID: PMC8500338.

4.  Moeen et al., Minerva Anestesiologica (November 2022):

5.  Guven, D. G., Demiraran, Y., Sezen, G., et al. (2011). Comparison between dexmedetomidine and remifentanil for controlled hypotension and recovery in endoscopic sinus surgery. Annals of Otology, Rhinology & Laryngology, 120(9), 586–592.

6. Ding, D.-F., et al. (2017). Target-controlled infusion of propofol and remifentanil combined with dexmedetomidine reduces functional endoscopic sinus surgery bleeding. Experimental and Therapeutic Medicine, 14(5), 4521–4526. doi: 10.3892/etm.2017.5075.

7. Warner BK, Munhall CC, Nguyen SA, Schlosser RJ, Guldan GJ 3rd, Meyer TA. Dexmedetomidine and surgical field visibility in nasal surgery: a systematic review and meta‑analysis. Journal of Perioperative Practice. Online ahead of print June 3, 2024

Routine Sugammadex for NDMB reversal

 I recently changed jobs and joined a hospital based anesthesia group at a busy downtown facility in my area.  There were many adjustments needed to accommodate a different cultural practice.  For example, on my first day of work I was assigned to do my own case for a IM nail in an elderly gentlemen who had a hip fracture.  In the past 5 years I had adjusted over time to opting for an LMA in many of these cases if I deemed it appropriate.  In this patient I placed an LMA only to have the surgeon come to me and tell me that she required general anesthesia for these types of cases.  I explained to her that the patient was under general anesthesia.  She said, No, I need the patient paralyzed.  I explained that could be accomplished if needed despite having an LMA. Then she said to me that no one uses LMAs for these cases and that going forward she would expect an ETT for all further cases.   This was quite a novel experience for me and represented a new cultural that I had to adjust to.  

However, my discussion for today is related to the use of neuromuscular blockade and reversal that permeates my new anesthesia department.  In my previous practice, where my group covered approximately six different hospitals, Sugammadex was somewhat restricted and could only be accessed from a central Pyxis or directly from the hospital pharamacist due to high cost.  This was not the case at the facility I had transferred to.  Of course, I loved having Sugammadex in the Pyxis available should I need it.  However, our department was getting continual notices of over use of Sugammadex by our hospital pharmacist who asked our department to curtail its use due to cost.  Therefore, our leadership sent an email to the department asking for its help in restricting the use of Sugammadex.  I watched to see how practice would change  and noticed that Sugammadex was the go to reversal agent of all of the CRNAs I worked with.  More concerning was the educational experience of our resident nurse anesthetists.  They were all being systematically trained to simply give large doses of rocuronium which could easily be reversed with a standard 200 mg suggamadex dose at the end. Thus, when I questioned an RRNA regarding appropriate use of neostigmine it became obvious that they were largely untrained in its use.  I started asking my CRNAs to make it a goal to reverse with glycopyrrolate and neostigmine.  This resulted in the CRNAs using this first and then using Sugammadex to rescue failed reversal which was very common.  The CRNA assumed that a glycopyrrolate/neostigmine reversal was not possible because they were always needing to rescue with suggamadex.  

Essentially, the new culture of routine Sugammadex reversal that had emerged created a culture of inability to properly use neuromuscular blockade without Sugammadex.  Finally, we had an adverse event where a patient became apneic in PACU and required emergent rescue with additional Sugammadex.  In looking at the case it was noticed that the patient was a frail and weighed 50 kg.  They had received an initial 50 mg of rocuronium for intubation and then towards the end of the case (about 1 hour prior to finish), they had received a second single 50 mg dose of rocuronium for an unknown reason. It can be supposed that the surgeon complained about the patient not being “relaxed enough”, but it’s not clear.  However, this represents an extreme example of the average culture of neuromuscular blockade in our institution resulting from the immediate availability of Sugammadex which is given per routine in a 200 mg dose without concern for progression of TOF through the case, patient characteristics, or actual neuromuscular blockade requirements. More concerning is the fact that our students are learning these concepts.

The concept in medicine of only administering medications that are needed applies here.  I feel that OR culture has become very cavalier with medication administration, where often medications are given prophylactically when in many cases the baseline risk is very low.  Clinicians seem to consider the risk associated with giving medications.  This is very true as it relates to management of neuromuscular blockade.  For example, I often see full and deep neuromuscular blockade used for ORIF of the ankle or wrist or many other cases that really don’t need much if any neuromuscular blockade.  Furthermore, when it is used, it is not uncommon for 20 mg of rocuronium to be given q60 min regardless of the patient characterisitics or surgical requirements.  Presumably this is done to absolutely guarantee full paralysis with 0 chance of patient movement.   

Recently the ASA published guidelines related to reversal of neuromuscular blockade.  The goal of the guidelines was to highlight the concerns of not monitoring the train of four during anesthesia and also of not using quantitative monitoring of train of four resulting in residual neuromuscular blockade in the PACU leading to potential morbidity.  In the guidelines, one of the recommendations is to “use Sugammadex INSTEAD of neostigmine for deep or moderate neuromuscular blockade induced by rocuronium.”  Of course, anyone reading these guidelines casually could easily come away from the reading with the general idea in their mind that the ASA now recommends Sugammadex be used whenever rocuronium or vecuronium is used.  

I would argue that Sugammadex should be an alternative to neostigmine only when required given unique clinical scenarios.  In my practice I use Sugammadex about three times a year.  I will provide below a rationale for this practice.

1) I recognize that every time I give a medication there is the potential for an adverse reaction to the medication.  

Adverse reactions associated with rocuronium: In a large review published in 2016 [1], it was noted that in france between 2005 and 2007, the most common cause of anaphylaxis during anesthesia was reportedly NMBAs (47.4%).  This was followed by latex (20%) and antibiotics (18%).  In the journal Anesthesiology, Reddy at al. Found that the incidence of anaphylaxis was about 1:2500 with rocuronium, 1:2000 with succinylcholine, but 1:22,000 with Atracurium. In another long term comprehensive review in Western Australia of the incidence of anaphylaxis with different NMBAs, Sadler et al showed that rocuronium was responable for 56% of the cases of NMBA anaphylaxis, succinylcholine 21%, vecuronium 11%.   In summary, the thoughtful anesthesia provider always considers the risks associated with the administration of each drug.  Given that Rocuronium and Succinylcholine are among the most egregious offenders in this regard, their use should be used with caution and when necessary.  It could be argued that given the following, rocuronium should be used sparingly the exact opposite of what happens in routine clinical practice.  It also should be recognized that if rocuronium is used, the obvious next question should be, do I need to redose or dose for aggressive neuromuscular blockade throughout the case, or is it possible to allow the blockade to wear off naturally thus requiring little or no reversal toward the end of the case if adequate monitoring indicates that it is unnecessary.  If aggressive neuromuscular blockade is used throughout the case until the end, it should be indicated.  I would argue that it is borderline unethical practice to maintain aggressive neuromuscular blockade during a case that does not require it.  Not only does it increase the chance of intraoperative awareness, but it will demand reversal during emergence introducing another potential source of adverse events.  Serious allergic reactions to glycopyrrolate and neostigmine are considered extremely uncommon.  Therefore, for this reason alone, great consideration should be given to using these agents when reversal is required as first line.  This was highlighted by a recent journal article [4] published in 2020 where the authors found that in a review of over 49,000 patients none had a recorded allergic reaction to neostigmine whereas six experienced anaphylaxis with Sugammadex.  However, the package insert from Merck reports a much higher incidence of 0.3% hypersensitivity reaction in healthy volunteers [5]. The chances for experiencing a hypersensitivity reaction or anaphylaxis to Sugammadex are increased in a dose response manner as reported by de Kam at al [6].  Therefore, IF Sugammadex is required, the smallest dose needed to accomplish the goal should be used.  In 2019, the POPULAR study was published finding that the use of neuromuscular blockade during surgery was associated with increased post operative pulmonary complications (POPC).  There was a great deal of criticism of this study, but the most conservative take away from this study is that in real life clinical practice, practioners are not safely implementing neuromuscular blockade which is leading to morbidity.  A sub study of the POPULAR study was subsequently published showing that in patients who had a TOF >95% there was no increase in POPC.  I would argue that achieving this level of reversal in routine clinical practice is difficult.  This data suggests that neuromuscular blockade is likely overdosed in general and is associated with morbidity beyond the combined risks associated with hypersensitivity type reactions to  rocuronium.

Sugammadex has been linked to other adverse reactions as well. In oct 2024,  the Journal of Clinical Anesthesia [8] reported on events reported to the FDA Adverse Event Reporting System (FAERS) from 2009 to 2023. A total of 1453 reports were linked to Sugammadex.  Of note, were cases of severe bradycardia, 3rd degree AV block  and even PEA associated with Sugammadex. More concerning are reports of coronary artery vasospasm (referred to as Kounis syndrome in the literature).  Therefore, it has been recommended that atropine and epinephrine be readily available when using Sugammadex.  Importantly, the following graph showing events reported to the FAERS should be very concerning to any practitioner who routinely employs Sugammadex for reversal. 

2) I recognize that there is an economic impact of my practice which on a large scale has societal impacts.

Currently healthcare spending in the US has increase greater than inflation over a 20 year period.  In 2022 healthcare spending was 17.3% of GDP and increased to 17.6% of GDP in 2023.  I don’t have data for 2024 as of yet.  However, these real dollars are not necessarily associated with superior health outcomes.  This represents nearly $5 trillion US. Despite this staggering sum, there are hundreds of thousands of Americans who put off or avoid medical care due to scarcity.  Therefore, practioners have a moral and ethical obligation to understand the economic impact of the care they provide.  I believe that equally excellent care can often be provided with less cost if providers spend a little extra time contemplating the economic footprint of the care they provide. Anesthesia departments whose culture fosters the routine use of deep neuromuscular blockade for most general anesthetics that forces routine use of high dose Sugammadex to rescue normalizes expensive healthcare.  No thoughtful provider would do this consciously, leading me to conclude that culture is what drives this practice.  Largely, this is driven by fear of the surgeons reaction to any degree of perceived “tightness” in the patient. While there is no easy answer to overcoming the potential for conflict in the OR as it relates to neuromuscular blockade, the thoughtful practioners will use introspection to consider the benefits of guaranteeing the surgeon never complains at the expense of delivering lower value to society in general.

Before I conclude, I would like to update this post with a recent CLINICAL FOCUS REVIEW published in the journal Anesthesiology this month (July 2025) [10].   I would like to quote a few lines from this review and then provide quick commentary.  First, the authors write, “Based on the 2020 study and NAP6, it seems that the rocuronium-sugammadex combination is associated with more anaphylaxis than atracurium-neostigmine (19 cases vs. 4 cases per 100,000 patients).” At the end of the article they write, “Sugammadex anaphylaxis is rare (less than 0.02%), but also may be life threatening, and the compounding risk associated with NMBD allergy also needs to be considered.”  First, I would like to note that in the first quote, the authors compare roc-sug to atracurium-neostigmine.  As indicated above in this article, the incidence of allergic type reactions to atracurium is elevated at least compared to vecuronium. And even still the chance of having an allergic reaction to rocuronium-Sugammadex is 4 X that of atracurium.  They note that Sugammadex anaphylaxis is rare, thus seeming to ignore that it is far higher when compared to other therapies.  Certainly, on a population level it might be “rare”, but in anesthetics practice, patients are only interested in what happened to them.  In other words, if you wake up in the ICU after a routine outpatient procedure because you experienced a life threatening adverse reaction to rocuronium or to Sugammadex, you will not be interested to know that it was an a priori unexpected reaction given population statistics.  You will be even more upset if someone explains to you that the Sugammadex was used as a per routine when neostigmine would have been sufficient.  Seen from this perspective, I would argue that we should individualize care, avoiding higher risk medications if lower risk medications are APPROPRIATE and available.

In conclusion Sugammadex has had a net positive influence on our ability to safely administer anesthesia.  However, given how effective Sugammadex is at reversing neuromuscular blockade it is leading to  a cultural shift in anesthesia whereby practitioners now stop thinking about the art of neuromuscular blockade reverting to an algorithmic one size fits all approach.  Given that Sugammadex is currently very expensive with dose related side effects it would be prudent for all anesthesia practioners to carefully consider whether a case truly needs ANY neuromuscular blockade, whether the requirement is ongoing or can be allowed to wear off, and if not whether glycopyrrolate/neostigmine in low doses are appropriate for reversal prior to relying on Sugammadex.  I have found that I often do not need any neuromuscular blockade. I use LMA for many cases thus avoiding blockade for intubation.  In cases where the patient will need some degree of blockade I consider using succinylcholine to secure intubation which will not require any reversal.  If I opt for a NDBA I opt for smaller doses and for any ongoing needs I consider whether opioids might be used instead of neuromuscular blockers.  I rely on TOF monitoring which is fortunately provided by our institution and often find that with careful titration of the anesthetic I do not need to reverse any neuromucular blockade or if so, I may use a very small dose of glycopyrrolate and neostigmine.  In the meantime,  I watch in dismay as I see episodes of rescue Sugammadex being given in the PACU or hear collegues regale me of episodes of  severe life threatening bradycardia requiring aggressive intervention to avert disaster.

1. Takazawa T, Mitsuhata H, Mertes PM. Sugammadex and rocuronium-induced anaphylaxis. J Anesth. 2016 Apr;30(2):290-7. doi: 10.1007/s00540-015-2105-x. Epub 2015 Dec 8. PMID: 26646837; PMCID: PMC4819478.

2. Reddy JI, Cooke PJ, van Schalkwyk JM, Hannam JA, Fitzharris P, Mitchell SJ. Anaphylaxis is more common with rocuronium and succinylcholine than with atracurium. Anesthesiology. 2015 Jan;122(1):39-45. doi: 10.1097/ALN.0000000000000512. PMID: 25405395.

3. Sadleir PH, Clarke RC, Bunning DL, Platt PR. Anaphylaxis to neuromuscular blocking drugs: incidence and cross-reactivity in Western Australia from 2002 to 2011. Br J Anaesth. 2013 Jun;110(6):981-7. doi: 10.1093/bja/aes506. Epub 2013 Jan 18. PMID: 23335568.

4. Orihara M, Takazawa T, Horiuchi T, Sakamoto S, Nagumo K, Tomita Y, Tomioka A, Yoshida N, Yokohama A, Saito S. Comparison of incidence of anaphylaxis between sugammadex and neostigmine: a retrospective multicentre observational study. Br J Anaesth. 2020 Feb;124(2):154-163. doi: 10.1016/j.bja.2019.10.016. Epub 2019 Nov 30. PMID: 31791621.

5. ® Prescribing Information: Accessed on March 29, 2018. https://www.merckconnect.com/bridion/dosing.html?gclid=CjwKCAjwwPfVBRBiEiwAdkM0HRmYcD7oNbtdcOS7t1oDoUuYjy4YMCBaNzrdE3x3zTCLAboW4mMMwxoCF5cQAvD_BwE&gclsrc=aw.ds. Accessed March 2018 .

6.  de Kam PJ, Nolte H, Good S, Yunan M, Williams-Herman DE, Burggraaf J, Kluft C, Adkinson NF, Cullen C, Skov PS, Levy JH, van den Dobbelsteen DJ, van Heumen ELGM, van Meel FCM, Glassner D, Woo T, Min KC, Peeters PAM. Sugammadex hypersensitivity and underlying mechanisms: a randomised study of healthy non-anaesthetised volunteers. Br J Anaesth. 2018 Oct;121(4):758-767. doi: 10.1016/j.bja.2018.05.057. Epub 2018 Jul 13. PMID: 30236238.

7. Kirmeier E, Eriksson LI, Lewald H, Jonsson Fagerlund M, Hoeft A, Hollmann M, Meistelman C, Hunter JM, Ulm K, Blobner M; POPULAR Contributors. Post-anaesthesia pulmonary complications after use of muscle relaxants (POPULAR): a multicentre, prospective observational study. Lancet Respir Med. 2019 Feb;7(2):129-140. doi: 10.1016/S2213-2600(18)30294-7. Epub 2018 Sep 14. Erratum in: Lancet Respir Med. 2019 Feb;7(2):e9. doi: 10.1016/S2213-2600(18)30467-3. PMID: 30224322.

8. Mao X, Zhang R, Liang X, Liu F, Dai Y, Wang M, Huang H, Fu G. A pharmacovigilance study of FDA adverse events for sugammadex. J Clin Anesth. 2024 Oct;97:111509. doi: 10.1016/j.jclinane.2024.111509. Epub 2024 Jun 15. PMID: 38880003.

9. Hunter JM, Naguib M. Sugammadex-induced bradycardia and asystole: how great is the risk? Br J Anaesth. 2018 Jul;121(1):8-12. doi: 10.1016/j.bja.2018.03.003. Epub 2018 Apr 13. PMID: 29935599.

10.  Savic L, Silversides J, Leslie K, Sugammadex Anaphylaxis: Mechanisms, Diagnosis and Incidence. V. 143. (7) 2025 Anesthesiology.

40 year old female with severe cachexia for removal of breast implant

 Today I was assigned to take care of 40 year old female who had had a previous breast augmentation 14 years ago and then subsequently developed a multitude of problems including difficulty eating with severe weight loss requiring placement of a gastro jejunostomy feeding tube.  Today she weighed 47 kg and had developed a sacral decubitus ulcer and was using a wheel chair to get around.  She blamed all of her recent health problems on her implants asserting that the material in the implants had caused her body to react to it resulting in a long list of daily symptoms including nausea, headaches, weakness, difficulty swallowing, delayed gastric emptying and so on.  I performed a GETA with propofol succynlcholine induction, 2 mg hydromorphone and versed pre op.  I also worked in small doses of precedex intermittently throughout the case with intermittent small dose (10 mg) ketamine.  I applied a BIS monitor.

The patient developed initial hypotension on induction which I treated initially with phenylephrine, then vasopressin (1 unit) when she didn't respond to two doses of phenylephrine.  In doing all of this, I aggressively attempted to maintain a constant minute ventilation.  My goal was to see if I could see an increase in etCO2 in response to vasopressor administration which would indicate that the patient had improved cardiac output in response to the administration of alpha agonist.

This concept has been looked at in a number of studies.  In one study, it was determined that etCO2 was a better predictor of fluid responsiveness than other measures such as PPV, or SVV as measured using invasive arterial line pulse contour analysis.  Other studies have not been able to demonstrate a positive correlation between etCO2 changes in relation to cardiac output.  Another important concept to understand and look into is the physiology of why our patients develop hypotension and what is happening to the cardiovascular system when a vasopressor is administered to treat anesthetic induced hypotension.  I have already discussed these concepts in other posts, but I'd like to revisit this topic with additional studies and any updates since my last posts.

Broadly, when anesthesia is administered via a propofol induction dose, cardiac contractility is decreased as well as vasodilation.  It is assumed by many practioners that by giving a dose of phenylephrine, the SVR (via arteriolar vasoconstriction) is increased and thus BP is improved.  If we consider the equations relating to MAP, SVR & CO we will see that CO = SV X HR.   MAP = CO x SVR. Therefore, MAP = SV X HR X SVR.  As can be seen, during an anesthetic the MAP can drop as a result of a decrease in HR, SV, or SVR.  Therefore, if we can diagnose the cause of the drop in MAP, we can treat that component.  Typically, the drop in MAP that we see related to anesthesia is predominantly from a decrease in SV. However, there are three reasons SV can decrease: 1) decrease in cardiac contractility, 2) a decease in preload, and 3) an increase in SVR.  Therefore, in the vast majority of cases where we see a decrease in MAP with induction of anesthesia, it’s not unreasonable to attribute this to a decrease in SV. 

Understanding prelaod in this scenario therefore, can be helpful.  In general, preload is related to the mean systemic filling pressure.  The mean systemic filling pressure is a concept that visualizes the static pressure in capacitance vessels when there is no blood flow.  In this paradigm, there are two volumes of blood effectively, the stressed volume and the unstressed volume.  The so called "unstressed" volume is the volume of blood that is not participating in heart filling or systemic filling pressure.  It is essentially lost to the body for all intents and purposes.  When anesthesia is induced, the capacitance vessels (as well as all vasculature) relaxes.  This immediately reduces the preload by a fair amount.  A recent study showed that in healthy patients presenting for surgery, an induction dose of propofol decreased the mean systemic filling pressure (MSFP) in every single patient [1].  The implication of this study is that propofol induces hypotension by removing fluid from the effective or stressed volume and placing it in the the so called unstressed volume where it no longer participates in circulation.  This results in decreased preload and hypotension.  After intubation, mechanical ventilation can further impede venous return exacerbating the problem. 

The current paradigm in most anesthetic practices is to treat hypotension on induction with fluid boluses.  Clinicians believe that pre load can be increased by increasing total fluid volume available.  In otherwise healthy patients who receive 1 to 2 liters of crystalloid to treat perceived  hypovolemia, little detriment to health is encountered. However, most patietns presenting for surgery are very nearly euvolemic.  Some may be slightly hypervolemic.  Therefore, if we bolus large amounts of fluid to these patients to treat an anesthetic induced increase in unstressed fluid volume, we run the risk of the patient becoming hypervolemic when this same volume is returned to the stressed volume upon emergence from anesthesia.  It is known that the capacitance vessels (venous vessels) contain around 70% of the blood volume and these same vessels are far more compliant than arterial vessels.  The venous vessels are also more densley populated with alpha receptors.  Therefore, using small doses of phenylephrine to treat a decrease in MSFP related hypotension makes physiologic sense when we consider our patients to be essentially euvolemic upon presentation.  There is data to suggest that when a drop in blood pressure is related to a decrease in pre load, phenylephrine increases blood pressure by increasing pre load resulting in an increase in cardiac output [2] & [4].  Another way to word the above is that in patients whose hypotension is pre load dependent, phenylephrine is likely to increase blood pressure via an increase in SV (I.E. CO), whereas, in patients whose hypotension is preload independent, phenylephrine may increase blood pressure via increased SVR and likely will result in a decrease in CO in this scenario.  It must be emphasized that a patient whose hypotension is pre load dependent does not mean that the patient is hypovolemic.  It simple means that the patient needs more pre load, and this can occur by recruiting blood pooled in the non stressed blood volume of the patient, by giving additional fluids or both. This concept, however, remains debated amongst practicing anesthesiologists.  Until recently, no studies demonstrating that phenylephrine can increase blood pressure via an increase in SV have used the classic gold standard technique of measuring cardiac output via an indicator dilution method.  Indicator dilution CO-monitoring is based on the Stewart-Hamilton principle that blood flow can be determined from the rate of change in the concentration of a substance added to the blood stream. This method is notably not affected by alterations of vascular tone.  Recently, a study using indicator dilution CO monitoring in patients under GA in a head up position to induce pre load dependent hypotension was published demonstrating that phenylephrine does indeed increase stroke volume in these patients as the means of increasing blood pressure [5]. In this study, all patients also had SVV measured. In all patients, SVV was greater than 12% (indicating pre load dependent hypotension) after GA induction and prior to infusion of phenylephrine.  After infusion of phenylephrine, SVV decreased to on average 6%, CI increased on average by 18%, and the MAP increased on average by 20 mmHg.

Unfortunately in routine clinical practice it is not practical to measure cardiac output during most cases. Therefore, we can't be certain that a patient who develops hypotension has suddenly had a decrease in pre load, nor can we be certain that treatment with phenylephrine resulted in a higher cardiac output from improvement in the patient's pre load.  Fortunately, there is some evidence that etCO2 does positively correlate with cardiac output [3]. More recently, a meta analysis of six trials looking at the passive leg raise to acutely raise pre load  in mechanically ventilated patients was able to that change in etCO2 correlated with pre load changes with a pooled specificity of 0.9 and sensitivity of 0.79 [6].

In summary, in many cases, patients will become hypotension after induction to a degree that is unexpected. The astute anesthesiologist will already have a working presumption of the patient’s volume status prior to induction.  This a priori supposition will guide next steps.  However, if immediately initial interventions do not produce the expected result, it is prudent to consider whether utilization of changes in etCO2 to clinical interventions is merited. It is important to remember that changes in etCO2 are affected by basic CO2   Production, minute ventilation, and pulmonary blood flow (which is correlated to CO).  In these situations, if a small dose of phenylephrine produces an increase in etCO2 (all other things being equal), it’s reasonable for the clinician to conclude, that phenylephrine was able to recruit blood volume from a recruitable space (unstressed volume) into the effective circulatory system.   Again, this will not indicate whether the patient is hypovolemic or euvolemic, but does prove that the patient is pre load dependent, and EITHER fluids or phenylephrine can be an effective treatment.  

1. Zucker, M., Kagan, G., Adi, N. et al. Changes in mean systemic filling pressure as an estimate of hemodynamic response to anesthesia induction using propofol. BMC Anesthesiol 22, 234 (2022). https://doi.org/10.1186/s12871-022-01773-8

2. Kalmar AF, Allaert S, Pletinckx P, Maes JW, Heerman J, Vos JJ, Struys MMRF, Scheeren TWL. Phenylephrine increases cardiac output by raising cardiac preload in patients with anesthesia induced hypotension. J Clin Monit Comput. 2018 Dec;32(6):969-976. doi: 10.1007/s10877-018-0126-3. Epub 2018 Mar 22. PMID: 29569112; PMCID: PMC6209056.

3. Lakhal K, Nay MA, Kamel T, Lortat-Jacob B, Ehrmann S, Rozec B, Boulain T. Change in end-tidal carbon dioxide outperforms other surrogates for change in cardiac output during fluid challenge. Br J Anaesth. 2017 Mar 1;118(3):355-362. doi: 10.1093/bja/aew478. PMID: 28186263.

4. Cannesson M, Jian Z, Chen G, Vu TQ, Hatib F: Effects of phenylephrine on cardiac output and venous return depend on the position of the heart on the Frank-Starling relationship. Journal of applied physiology 2012, 113(2):281-289.

5. Højlund J, Cihoric M, Foss NB. Vasoconstriction with phenylephrine increases cardiac output in preload dependent patients. J Clin Monit Comput. 2024 Oct;38(5):997-1002. doi: 10.1007/s10877-024-01186-7. Epub 2024 Jun 21. PMID: 38907106; PMCID: PMC11427527.

6. Huang, H., Wu, C., Shen, Q. et al. Value of variation of end-tidal carbon dioxide for predicting fluid responsiveness during the passive leg raising test in patients with mechanical ventilation: a systematic review and meta-analysis. Crit Care 26, 20 (2022). 

Surgical Site infection: where are we now in terms of intraoperative oxygen therapy

 Since I last updated my blog related to perioperative surgical site infections and oxygen tension, several articles have appeared related to this topic. I would like to update my blog with the latest information to provide context to the highly charged debated related to intraoperative FiO2.

Just this year, an editorial review was published [1], going over the pros and cons of perioperative hyperoxia as it relates to SSI.  Larvin et al. appropriately note that oxygen delivery (DO2) does not depend on PaO2, but rather on the Cardiac Output and oxygen content of blood, which is largely dependent on saturation and hemoglobin. Futhermore, they correctly note studies have found that NAPDPH oxidase enzymes driving 'respiratory burst' to produce reactive oxygen species (ROS) that are critical in bacterial killing by neutrophils depend on PaO2 NOT CaO2.  Unfortunately, Larvin et al. stop here and fail to review the literature looking at oxygen tension at tissue levels and how it relates to bacterial killing by neutrophils, as well as how tissue oxygen tension is related to PaO2.  In truth, PaO2 while better than CaO2 as a surrogate, is still a surrogate for tissue oxygen tension (To2) where the actual bacterial killing is to take place.

The editorial review also covers the WHO recommendations in 2016 and revision in 2018 where it is recommended to use FiO2 of 0.8 in order to reduce SSI.  Several months prior to the WHO recommendations, a cochrane review was published wherein they stated that there was insufficient evidence that hyperoxia was beneficial.  To make it more confusing, in 2017,  CDC  also released a statement supporting the use of high FiO2 in intubated surgical patients.   

Shortly after these recommendations, in 2019, De Jonge et al. [2] republished their previous meta analysis after including studies that had been done since their previous review.  They determined that SSI indeed were decreased by using 80% oxygen vs. 30 to 35% oxygen.  However, this was the case only in intubated patients.  Obviously, the ability of high FiO2 to reduce SSI is dependent on the risk of SSI being high to start with.  In surgical cases where patients do not require intubation, the risk for SSI at baseline is likely low, and thus, any intervention is not likely to be found to be helpful. 

Much of the controversy related to hyperoxia during surgical procedures is related to the idea that oxygen is toxic to the lungs.  In 2017 Staeher-Rye et al [3] published a study concluding that the incidence of post op pulmonary complications (PPCs) at day 7 was higher in those with a higher median FiO2 during surgery even after adjusting for potentially confounding variables.  However, this was a retrospective database review where only 8% of the charts reviewed had appropriate data to analyze.  While statistical techniques can adequately control for a number of variables, the prospective RCT is still the gold standard and thus, retrospective reviews should not typically drive clinical practice. Indeed, one can easily imagine that in typical surgeries, most anesthesiologists will titrate the FiO2 to the patients condition. Thus, patients who are not doing well from an oxygenation stand point and thus very likely to go on to develop complications post op are also most likely to have higher intraoperative FiO2.  The cues that prompt this titration may be subtle and not easily extracted from an administrative database.   In 2018 Kurz, A et al. published a study where the oxygen concentration in an isolated suite of ORs was alternated between 0.8 and 0.3 every two weeks.  Unfortunately, while this was a well done study there were a few issues that made the results less compelling. First, the 30% group received a higher percentage than 30% and even ranged up to near 80% in some patients. Second, they looked at 30 day composite which included SSI.  There is some question as to whether counting SSI that occur 20 to 30 days after surgery is a realistic end point to measure the impact of intraoperative oxygen delivery.  Third, there was no attempt to control oxygen delivery after surgery which was part of the protocol in previously done studies that did find a benefit of perioperative hyperoxia.  Fourth, the rate of infection in both groups was very low (4.1% in FiO2 0.8 vs. 3.9% in FiO2 0.3).  This low rate may not be reflective of SSI rate at other hospitals. Furthermore, although not highlighted in the study, in a small blurb near the end of the paper, it is noted that patients in the 0.8 group had a lower SSI risk for superficial SSI (5.2%) vs. those in the 0.3 group (6.4% p=0.047). In the discussion the authors state that a decrease in superficial SSI is not serious enough to merit the use of hyperoxygenation.  I would argue that this statement reveals a clear underlying bias of the authors against oxygen therapy; likely a reflection of the authors fears that hyperoxia will cause post op pulmonary complications.  Also in the discussion the authors make an important point.  They state, "Even 30% inspired oxygen typically produces tissue partial pressure near 60 mmHg."  At a tissue partial pressure of 60 mmHg, they argue, bactericidal affects are adequate to prevent infection by oxidative killing by neutrophils.  This line of reasoning comes from a study done earlier where it was identified that neutrophil oxidative killing increases up to a maximum of tissue oxygen tension of 300 mmHg.  This same paper noted that 1/2 oxidative killing occurred in a range from 45 mmHg up to 80 mmHg.  Provided this information, shooting for a tissue partial pressure of oxygen of 60 mmHg as mentioned above and to be expected with an FiO2 of 0.3 in a normal healthy patient gives no room for error and does not account for the outliers where 1/2 oxidative killing does not occur until partial pressure of oxygen in the tissues is closer to 80 mmHg.

In 2023, [4]  another meta analysis was published revisiting all studies on oxygen delivery in patients undergoing abdominal surgery.   The authors concluded that the application of high concentration of oxygen was able to reduce SSIs with the caveat that the quality of the studies included were considered moderate to poor.  This same year, yet another meta analysis was published [5] and found no benefit of high inspired oxygen; however, in a subgroup analysis, they found that high oxygen levels did reduce the incidence of SSI when excluding anesthetics done under regional anesthesia.  They noted that a large number of the procedures that were included in the 'regional anesthesia' group included cesarian sections done under spinal or epidural anesthesia. For a number of reasons SSI after c/s is not likely.  Furthermore, it has been well demonstrated that regional anesthesia and particularly neuraxial anesthesia can dramatically increase  tissue partial pressure of oxygen likely as a result of significant vasodilation below the block level.  

 Recently,  Mattishent K et al published a large systematic review [6] concluding that high (80%) oxygen concentration is not associated with increased harm compared to lower oxygen concentrations (30-35%).  The same year as this systematic review was published a post hoc analysis was completed on a large cohort study [9], wherein it was confirmed that FiO2 of 0.8 is not associated with increased pulmonary complications post operatively.  Furthermore, there has been concern raised that hyperoxia can worsen myocardial ischemia in the at risk patient due to oxygen induced vasoconstriction.  However, a meta analysis of three studies found no increased cardiovascular adverse events in patients treated with intraoperative hyperoxia [6].  When pigs were subjected to haemodilution until their electrocardiogram showed ischaemic changes, hyperoxia, although it caused coronary vasoconstriction and reduced coronary blood flow, preserved myocardial oxygenation and improved electrocardiogram abnormalities [10].  Some have argued that since hyperoxia is associated with vasoconstriction, it shoud be avoided in patients at risk for stroke.  However, a recent published review of the literature was able to show that hyperoxia proved beneficial in the setting of acute ischemic stroke [8]. Another common concern is related to hyperoxia induced altelectasis.  In 2003 in Anesthesiology, Edmark et al. were able to quantify atelectasis from FiO2 of 1.0 compared to 0.8.  Here, when 0.80 FiO2 was used during anaesthesia induction, the atelectatic area in the basal lung fields as measured by computed tomography was reduced from 9.8 ± 5.2 cm2 (1.0 FiO2) to 1.3 ± 1.2 cm2(0.8 FiO2).  While hyperoxia has been demonstrated to induce vasoconstriction with a reflex decrease in stroke volume and cardiac output, this does not translate into a decrease in tissue oxygen partial pressure of oxygen. In fact, studies have made it clear that despite a slight decrease in cardiac output, oxygen partial pressure at the tissue level (PtO2) is increased.  This is because at the tissue level oxygen partial pressure levels are most related to PaO2, not oxygen delivery or DO2.

Finally, a further commentary on the current literature to date on the hyperoxia reducing SSIs.  The initial trials showing a benefit of hyperoxia were well done DB RCTs in colorectal surgery done in an open fashion.  Furthermore, patients in these earliers trials were treated with liberal fluid regimens to avoid hypovolemic vasoconstriction and minimize vasoconstrictors, both known causes of decreasing tissue level oxygen partial pressure. Importantly, in the first trial, oxygen partial pressure was actually measured and seen to improve in the hyperoxia group v. the lower oxygen group.  Later negative trials suffered from a number of problems.  Some included young healthy patients undergoing surgery at very low risk for SSI. None of the negative trials measure PaO2 or oxygen partial pressure in the tissues. Therefore, it is unknown if the hyperoxia treated patients actually reached therapeutic levels of oxygen in the tissues.  Lastly, some of the negative trials utilized more restricted fluid regimens, thus increasing risk of patients not having optimized perfusion of tissues thus lowering tissue oxygen partial pressure. 

Therefore, current evidence to this date looking at potential adverse events associated with intraoperative hyperoxia suggests that FiO2 of as high as 0.8 is safe.  This makes physiological sense given that surgeries are typically of short duration.  This cannot likely be extrapolated to critically ill patients coming to the OR suite from the ICU already requiring mechanical ventilation. These present unique situations where the lungs are exposed to hyperoxia over long periods of time often days on end.  In these situations, modification of inspired oxygen concentration is needed, recognizing that increasing tissue partial pressure of oxygen may be improved by improving other ventilatory paramters such as optimizing respiratory rate, Vt, and most importantly optimizing PEEP for the individual patient.

In summary, it is clear that in certain patient populations, hyperoxia does result in lower SSI incidence. Therefore, identification of this high risk sub group is important. Much of the debate related to high oxygen concentration vs low is related to a fear of causing patient harm with hyperoxia. However, given the current evidence demonstrating safety with hyperoxia, it makes sense to recognize the potential benefits in certain patients while recognizing the potential for harm in limited and specific scenarios.    As usual, a nuanced approach to oxygen delivery is probably best.  For example, hyperoxia and optimization of PaO2 (supramaximal) should be considered in an emergent ex lap colectomy after colon perforation.  Whereas, lower oxygen levels might be considered (i.e. FiO2 0.3) for a critically ill patient being mechanically ventilated for the last week going to the OR for wash out of scalp laceration.  In the end, as the anesthesiologist, you must use your best judgement on how to titrate the oxygen levels weighing in between five and ten different clinical parameters that may affect your choice.

1. Larvin J, Edwards M, Martin DS, Feelisch M, Grocott MPW, Cumpstey AF. Perioperative oxygenation-what's the stress? BJA Open. 2024 Mar 20;10:100277. 

2. de Jonge S, Egger M, Latif A, Loke YK, Berenholtz S, Boermeester M, Allegranzi B, Solomkin J. Effectiveness of 80% vs 30-35% fraction of inspired oxygen in patients undergoing surgery: an updated systematic review and meta-analysis. Br J Anaesth. 2019 Mar;122(3):325-334.

3. Staehr-Rye AK, Meyhoff CS, Scheffenbichler FT, Vidal Melo MF, Gätke MR, Walsh JL, Ladha KS, Grabitz SD, Nikolov MI, Kurth T, Rasmussen LS, Eikermann M. High intraoperative inspiratory oxygen fraction and risk of major respiratory complications. Br J Anaesth. 2017 Jul 1;119(1):140-149

4. Kuh, J.H., Jung, WS., Lim, L. et al. The effect of high perioperative inspiratory oxygen fraction for abdominal surgery on surgical site infection: a systematic review and meta-analysis. Sci Rep 13, 15599 (2023). https://doi.org/10.1038/s41598-023-41300-4

5. El Maleh, Y., Fasquel, C., Quesnel, C. et al. Updated meta-analysis on intraoperative inspired fraction of oxygen and the risk of surgical site infection in adults undergoing general and regional anesthesia. Sci Rep 13, 2465 (2023). 

6. Mattishent K, Thavarajah M, Sinha A, Peel A, Egger M, Solomkin J, de Jonge S, Latif A, Berenholtz S, Allegranzi B, Loke YK. Safety of 80% vs 30-35% fraction of inspired oxygen in patients undergoing surgery: a systematic review and meta-analysis. Br J Anaesth. 2019 Mar;122(3):311-324. doi: 10.1016/j.bja.2018.11.026. Epub 2019 Jan 3. PMID: 30770049.

7. Weenink RP, de Jonge SW, van Hulst RA, Wingelaar TT, van Ooij PAM, Immink RV, Preckel B, Hollmann MW. Perioperative Hyperoxyphobia: Justified or Not? Benefits and Harms of Hyperoxia during Surgery. J Clin Med. 2020 Feb 28;9(3):642. doi: 10.3390/jcm9030642.

8. Qijian Wang, Xiao Zhang, Yijun Suo, Zhiying Chen, Moxin Wu, Xiaoqin Wen, Qin Lai, Xiaoping Yin, Bing Bao, Normobaric hyperoxia therapy in acute ischemic stroke: A literature review, Heliyon, Volume 10, Issue 1, 2024,

9. Cohen B., Ruetzler K., Kurz A., Leung S., Rivas E., Ezell J., Mao G., Sessler D.I., Turan A. Intra-operative high inspired oxygen fraction does not increase the risk of postoperative respiratory complications: Alternating intervention clinical trial. Eur. J. Anaesthesiol. 2019;36:1–7. 

10. Kemming G.I., Meisner F.G., Meier J., Tillmanns J., Thein E., Eriskat J., Habler O.P. Hyperoxic ventilation at the critical hematocrit: Effects on myocardial perfusion and function. Acta Anaesthesiol. Scand. 2004;48:951–959

11. Edmark L., Kostova-Aherdan K., Enlund M., Hedenstierna G. Optimal oxygen concentration during induction of general anesthesia. Anesthesiology. 2003;98:28–33.

62 y/o female for breast reconstruction with daily marijuana use

 This morning my patient was a 62 year old female who uses marijuana daily.  She also reported to me that after a recent general anesthetic she experienced a two week period of amnesia immediately following her anesthetic. She stated that she performed all of her normal activities and that friend and family told her she behaved normally, however, she states that she has no recall of the events during these two weeks.

My anesthetic was a straight general endotracheal anesthetic using a propofol infusion for its benefits on PONV, and inhalation anesthesia to facilitate neuromuscular blockade during surgery as well as reduce the required propofol infusion dose.  I gave hydromorphone 2 mg up front with 2 mg of versed. I also gave 4 mg of decadron as we rolled to the OR. I placed a BIS monitor to evaluate her EEG in real time as well as her BIS.  I was particularly motivated to avoid burst suppression given her recent history of memory loss after anesthesia.  I suspected that perhaps the patient had developed some mild post operative delirium (POD), and increasing frequency of burst suppression during anesthesia is associated with increased rates of POD.

On induction, I gave the patient 110 mg of propofol. I noted that the BIS quickly went to about 20 and the burst suppression ration (BSR) increased to nearly 40%.  I was also able to note a flat EEG indicating burst suppression.  This indicated immediately to me that the patient likely had a vulnerable brain.  Therefore, I immediately planned for a lower setting on the sevoflurance concentration and propofol infusion. I titrated the sevoflurane to an ET% of 0.9 (MAC 0.4) and propofol of 75 mcg/kg/min.  However, with more time, her BIS recovered but then drifted lower.  I titrated the propofol infusion down to a minimum of 30 mcg/kg/min with the SEVO at 0.5 MAC (age adjusted).  At this level the BIS hovered  near 40 with BSR remaining at 0.  Due to the very low anesthetic dose I was providing I opted to give 5 mg vecuronium with small intermittent doses to reduce the chance of sudden movement. In fact, prior to incision and no stimulus to the patient and the BIS reading 39, the patient began coughing spontaneously. This highlights the fact that a BIS of 40 will NOT prevent patient movement during surgery.  This event prompted me to decide to maintain some degree of paralysis.  In my previous post on POD, I cited a study showing that the incidence of POD was decreased when the BIS was titrated to 50 vs. a BIS of 35.  I would emphasize that the patient's heart rate and blood pressure all remained suppressed but WNL during induction and the entirety of the case and did not seem to be entirely associated with her BIS level.

This patient was a daily marijuana user.  Marijuana is smoked for its THC content, which is an agonist at both the endocanabinoid 1 and 2 receptors. The CB1 receptor is found in the CNS. CB 1 receptors seem to primarily modulate pain, memory, and energy metabolism.  CB 2 receptors are located in both the CNS and immune cells and modulate the immune signaling as well as the inflammatory response. CBD also has actions on the 5-HT1a receptor (serotonin) in the CNS and platelets resulting in its anti nausea effects.  

Acute Marijuana use (canabinoid intoxication) results in a number of effects. These include tachycardia and vasodilation. In patients with CAD, this has resulted in increased incidence of angina and even MI (via demand ischemia).  Typically these affects resolve after 1 hour from canibinoid use.  Nevertheless, in a large retrospective review of over 27,000 records, the active cannabinoid users had increased odds of experiencing a myocardial infarction in the preoperative period.  Bronchodilation with hyperreactivity of the airways is also associated with acute cannabis use.  In the CNS, cannabis use causes anxiolysis or anxiety, paranoia or even frank psychosis, euphoria, dizziness, headache, memory dysfunction and analgesia. Furthermore, in young users the risk of stroke compared to tobacco smokers was 4.7 times higher.  This effect may be a result of the vasoconstriction effect on cerebral vessels of cannabis when hypoxia or hypercapnia is present. Furthermore, prolonged heavy use of cannabinoids results in hippocampal thinning and neuronal death. Acute cannabis use can also be an antiemetic as well as increasing appetite. Chronic daily users may see increased atheromatous disease, COPD or emphysema, and some may experience increased nausea and vomiting (hyperemesis).  In patients experience hyperemesis, severe abdominal pain is often an accompanying symptom. 

Typically chronic marijuana users presenting for surgery are stopping their use prior to arrival.  This presents the anesthesiologist with the possibility of withdrawal symptoms. Withdrawal symptoms include irritability, anger, aggression, anxiety, nervousness, insomnia, disturbed dreams, restlessness, depressed mood, anorexia, abdominal cramping, tremors, sweating, fevers, chills and headache. This withdrawal syndrome can last for several weeks in high dose chronic users.

Cannabis use and its effects on anesthetic requirements in humans have not been well studied.  In one study on admitted cannabis users demonstrated that they required significantly higher propofol doses than non users to achieve a BIS of < 60.  In another study, patients given a synthetic THC during a general anesthetic resulted in an increase in the BIS. From this study, it was not clear whether the increase in BIS represented a lightening of anesthesia, or the effects of the cannabis on the processed EEG.  Despite these studies, in my patient, it was clear that a small propofol dose had a profound effect on her BIS. Perhaps this is reflective of the effects of prolonged chronic cannabis use on the brain.  Unfortunately, we have no well done studies to establish this.  Nevertheless, I believe that given her reaction, it is at least prudent to be alerted to this possibility in older chronic daily marijuana users.  This may be a relative indication to place a pre induction BIS monitor on for better titration of induction agents.

Recently, during another case where I was working with a CRNA, we had a patient who used marijuana with some frequency.  The CRNA stated that the patient was at risk from aspiration and should be treated as if they were a "full stomach"; i.e. RSI with endotracheal intubation to prevent aspiration.  In a recent search of the literature, I was able to find a case report where a patient who was a heavy chronic marijuana user having an elective surgery with LMA, vomited during surgery and required emergent RSI intubation during the surgery.  The providers placed an OG tube and suctioned out 600cc's of gastric content.  In this article, the blame for the patient have gastric contents was placed on his use of marijuana.  In some cases, marijuana is associated with a hyperemesis syndrome. However, it is not clear that this is due to delayed gastric emptying, but rather results from cannabis effects on the vomiting center of the brain.  In 2023, an RCT was published where cannabidiol was used to treat patients with gastroparesis.  The authors were able to show in these patients that symptoms improved with cannabidiol.  Whether cannabinoids can decrease gastric emptying, it seems unclear.  Therefore, in patients with heavy cannabis use, it seems prudent to question them to determine if they have trouble with early satiety, nausea, vomiting or repeated belching and reflux.  If they are free of any of these symptoms, there is no evidence that heavy chronic cannabis users need to treated as if they have a full stomach.

With regards to intraoperative analgesia, again there are no well done studies to guide us. However, recent studies do indicate that cannabis users report higher pain scores, have worse sleep, and require more rescue analgesics in the immediate post operative period. Studies on cannabinoid agonists have shown that they facilitate endogenous opioid signaling and increase concentrations of endogenous opioids. In animal studies cannabinoids and opioids are synergistic 

Ketamine induces endogenous cannabinoid release which may partially explain its role in an anti-nociception.  However, the psychomotor side effects of ketamine are enhanced with CBD administration.  It also appears that gabapentin and cannabinoids act synergistically both acting in similar manner as activation of CB receptors results in inhibition of the voltage dependent calcium channel similar to gabapentin.  Thus care should be taken when gabapentinoids are part of an ERAS protocol and the patient is a heavy cannabis user.

In summary, patient coming to surgery who are chronic heavy users of marijuana seem to be at increased risk of perioperative strok and MACE.  Fortunately, the 1/2 life of THC is rather short, and therefore, it is unlikely that patients presenting for elective surgery will be directly affected by high levels of cannabinoids. However, it is well documented that acute cannabis intoxication will likely result in tachycardia with vasodilation, placing these patients at potential risk for hemodynamic instability. At this time it is unclear if chronic heavy users of cannabis have higher anesthetic requirements, although some studies suggest this.  In this case report, the patient have very low anesthesia requirements, and in fact, processed EEG monitoring suggested the patient had a vulnerable brain, driving me to significantly titrate down the anesthetic level to avoid post operative delirium.

1. Zheng T, BouSaba J, Taylor A, Dilmaghani S, Busciglio I, Carlson P, Torres M, Ryks M, Burton D, Harmsen WS, Camilleri M. A Randomized, Controlled Trial of Efficacy and Safety of Cannabidiol in Idiopathic and Diabetic Gastroparesis. Clin Gastroenterol Hepatol. 2023 Dec;21(13):3405-3414.