Case Reports in Anesthesia

Blog with interesting cases and/or problems related to anesthesia with discussion based on best evidence in the literature.

February 19, 2022

pituitary adenoma coming for surgery

 59 year old female for D&C and hysteroscopy with a history of pituitary adenoma, empty sella syndrome, Adrenal insufficiency, HTN, OSA, and BMI of 31. The patient was taking cabergoline to inhibit the secretion of prolactin via agonism of dopamine receptors. The patient also had a history of PONV and was very concerned with this prior to surgery.


The patient had been followed for several years for her pituitary adenoma and had had no recent changes in her medical status.  I verified that her labs were within normal limits and proceeded with a general anesthetic with LMA.


The pituitary gland occupies the sella turcica of the sphenoid bone at the base of the skull, the roof of which is created by an incomplete fold of dura, the diaphragma sella, through which passes the pituitary stalk.


Hormone and site of productionTarget organ and function
Anterior pituitary 
ACTH pars distalis Adrenal glands: stimulates the glands to produce glucocorticoids and aldosterone 
GH pars distalis Musculoskeletal system: anabolic effects on bone and muscle. Promotes lipolysis, increases free fatty acid levels, and impairs glucose utilization and cellular sensitivity to insulin 
Prolactin pars distalis Mammary glands: stimulates the glands to produce milk 
Ovary: inhibits the actions of gonadotropins on the ovary 
FSH and LH pars tuberalis Gonads: stimulate the testes to produce sperm and testosterone, and the ovaries to produce eggs and oestrogen 
TSH pars tuberalis Thyroid: stimulates the gland to produce thyroid hormones 
Beta-melanocyte-stimulating hormone pars intermedia Skin: causes increased pigmentation 
Endorphins and encephalins pars intermedia Brain and immune system: inhibits pain sensations 
Posterior pituitary 
Antidiuretic hormone Kidneys: regulates the amount of water excreted by the kidneys and maintains water balance in the body 
Oxytocin Uterus: contracts the uterus during childbirth and immediately after delivery 
Mammary glands: stimulates contractions of the milk ducts in the breast leading to the let-down reflex, which moves milk to the nipple in lactating women 

The posterior pituitary is regulated directly by the hypothalamic axons which project to it and synapse with its cells. The anterior pituitary is regulated by hypothalamic tropic hormones that reach it via the portal venous system. The hypothalamic influence is mainly stimulatory, which is in turn regulated by negative feedback control exerted at the pituitary and hypothalamic level, the classical example being the feedback regulation of thyroid-stimulating hormone (TSH) by the thyroid hormones

There are two main categories that facilitate tracking the practical considerations of approaching a patient with a pituitary adenoma. Macroadenomas (>10mm) and microadenomas (<10mm).   Larger tumours can cause hypopituitarism, cranial nerve palsies, and hydrocephalous due to blockage of third ventricle outflow. Microadenomas may present with symptoms of hormonal excess, the classic example being Cushing's disease [excess of adrenocorticotropic hormone (ACTH)] or very rarely thyrotoxicosis (excess of TSH).  

The three most common hypersecreting hormonal syndromes from pituitary adenomas include:

1) Acromegaly: 20% of pituitary adenomas. These are  macroadenomas secreting excess GH resulting in a constellation of comorbidities.
Patients coming to surgery with this type of tumor will be on medications to inhibit GH production such as Somatostatin analogues, Octreotide, lanreotide or GH receptor antagonist (Pegvisomant).
2) Cushing's disease:  A pituitary corticotroph adenoma secreting excess ACTH. These represent about 7% of pituitary adenomas. These patients may arrive to surgery taking ketoconazole, metyrapone, mitotane, or aminoglutethimide. These medications inhibit the enzymes in the adrenal gland that make up the chain of synthesis of cortisol and therefore, are able to reduce hypercortisolemia.  Patient's may be arriving to surgery to undergo bilateral adrenalectomy which is required for non resesectable ACTH hypersecreting microadenomas. These patients often suffer from HTN, DM and osteoporosis (40% of patients).
In particular, patients with Cushing's disease may present with hypokalemic metabolic alkalosis. Hypokalemia occurs due to overwhelming of the enzyme 11-beta-hydroxysteroid dehydrogenase by excessive circulating cortisol, resulting in inappropriate activation of the mineralocorticoid receptor.  This receptor allows for retention of sodium at the expense of spilling potassium and hydrogen ions into the urine at the distal convoluted tubule of the kidney.
3) Prolactinoma: Medical therapy is first line with bromocriptine or cabergoline (inhibit prolactin secretion). These medications will often resolve hyperporlactinemia and reduce tumor size.  There are no perioperative care issues caused by the physiological affects of prolactinomas. These tumors are far more common in females. In men, they are often macro adenomas.



Hormone Hyposecretion

1) Adrenal cortical insufficiency: This is also known as secondary adrenal insufficiency and differs from Addison's disease in that the electrolyte disturbances are less severe. In the perioperative period IV hydrocortisone along with IV normal saline +/- IV glucose is indicated for support to avoid hypotension.

As cortisol is produced in the adrenal cortex in the zone fasciculate via stimulation from ACTH, in some rare cases (i.e. pituitary apoplexy), the pituitary gland is rendered incapable of producing ACTH. While in secondary adrenal insufficiency the sodium and potassium are often normal, although in some instances, a dilution hyponatremia develops due to excess ADH secretion from absence of cortisol.  Dehydration and hyperkalemia are typical of primary adrenal cortical insufficiency due to faulty aldosterone secretion as well.  However, aldosterone is not primarily under the control of the PG, and therefore, not typical of secondary adrenal insufficiency.




In cases of addisonian crisis from secondary adrenal insufficiency as seen from a PG problem can be treated with dexamethasone 8 mg or hydrocortisone.  Since in secondary adrenal insufficiency aldosterone is adequate, the mineralocorticoid effects of hydrocortisone are not critical, and a pure glucocorticoid such as decadron is adequate for treatment.  However, NS should be infused as well, as opposed to LR, as hyponatremia may accompany this syndrome from SIADH.

2) Hypothyroidism:  Pituitary hypothyroidism tends to be less severe than primary thyroid failure. However, patients will be more sensitive to and less able to metabolize anesthetic medications. This can result in induction of anesthesia with very low dosages as well as prolonged sleep after discontinuation of anesthetic medications.   Clinical response to thyroid replacement therapy may take 10 days, although more rapid correction can be achieved with i.v. L-iodothyronine (T3). Unfortunately, there is a significant risk of precipitating myocardial ischaemia and heart failure.  Furthermore, Thyroid hormone replacement has to be done very cautiously in patients with impaired adreno-corticotrophic hormone ACTH reserves as it can precipitate an adrenal crisis. Therefore, glucocorticoid cover is essential before proceeding with thyroid hormone replacement.

3)  Central Diabetes Insipidus:  Far less likely to be encountered in the perioperative period. The result of failure of secretion of ADH. It is treated with desmopressin, a synthetic analogue of ADH that has a longer half life and which lacks the vasoconstricting properties of the endogenous hormone. Although desmopressin is usually administered orally or intra-nasally, after operation it can be given as a subcutaneous or intra-muscular injection. Failure to secrete oxytocin only becomes clinically evident during and after childbirth, and is not relevant in the acute setting.7
 

Surgical stress and hormonal changes


Pituitary
Adrenal
Pancreatic
Others
Increased secretion Growth hormone (GH) Catecholamines Glucagon Renin 
 Adrenocorticotrophic hormone (ACTH) Cortisol   
 β-Endorphin Aldosterone   
 Prolactin    
 Arginine vasopressin (posterior pituitary) (AVP)    
Unchanged secretion Thyroid stimulating hormone (TSH)    
 Luteinizing hormone (LH)    
 Follicle stimulating hormone (FSH)    
Decreased secretion   Insulin Testosterone 
    Oestrogen 
    Tri-iodothyronine (T3)

Opioids can suppress the hypothalamic and pituitary hormone response to surgery.  However, to cause complete suppression, very large doses are required (i.e. ~50 mcg/kg).

Acute IV opioid administration can have a stimulatory effect on prolactin secretion mediated by the mu-,Kappa-, and sigmoid opioid receptors in the hypothalamus.  In cases of prolactinemia induced by opioids, bromocriptine has been used successfully to decrease prolactin levels.

This patient was taking cabergoline a dopamine 2 receptor agonist.  Cabergoline has been found to be effective in 80% of women with prolactinomas.  Bromocriptine has lost favor mainly due to pharmacokinetic issues where it is required up to 3 or 4 times a day.  Cabergoline is long acting requiring dosing as little as twice a week. It is important to note that PONV can be affected by stimulation of D2 and D3 receptors. Antagonism of these receptors may decrease PONV. The mechanism involves blocking adenylate cyclase to reduce the amount of cAMP in neurons in the nucleus tractus solitarius and area postrema.  Commonly used D2 antagonists include reglan, and a newer agent name Barhemsys (amusulpride).  In this patient with a concern for PONV and taking a D2 receptor agonist that was long acting, rescue treatment with any D2 receptor blocker may prove less effective.  Therefore, with the patient's permission a scopolamine patch was placed on the skin prior to rolling into the operating room.  Opioids were minimized, ketorolac was provided to reduce opioid requirements, dexamethasone 4mg and zoltan 4 mg were given as prophylaxis. The patient did not experience any PONV. If the patient had required rescue therapy, promethazine was ordered for rescue.  Barhemsys is a newer alternative which has been shown to be moderately effective for rescue therapy in patients who have already received prophylaxis.  Unfortunately, Barhemsys is a D2/3 antagonist which presents two potential concerns in this patient. 1) it may not be able to bind to the D2 receptor given the presence of cabergoline (d2 agonist). 2) It can induce increased prolactin levels in normal patients.  However, it is not clear at all, that this would be a problem in a patient who is already properly treated with cabergoline.

Pituitary adenomas represent a potential large constellation of syndromes and diseases processes.  A careful understanding of the type of adenoma along with its included pathophysiology is important prior to providing anesthesia. Fortunately, most pituitary adenomas are prolactinomas which tend to be benign and very responsive to medical therapy with dopamine 2 agonists.  It must be recognized that alternative pharmacotherapy for PONV must be considered as the d2 agonist in these patients will likely make antagonism of the D2 receptor impossible.

February 7, 2022

Twins in patient with thrombocytopenia

 A 28 year G3P2 carrying twins vertex vertex, presents the day before induction for consultation with anesthesia.  She states that she was diagnosed with thrombocytopenia by MFM, and started on 10 mg of prednisone for a platelet count of 71K.  She has had two prior deliveries without epidural analgesia.  She plans on vaginal delivery this pregnancy without epidural analgesia.  


In a recent study published in the NEJM,  2,804 women were followed with twin pregnancy.  Those who planned for vaginal birth ended up getting a c-section 44% of the time. This study looked at mortality and morbidity in women and fetuses who had planned c-section v. planned vaginal delivery. There was no difference between groups in terms of outcome.  The study did exclude any patients whose twin A was in the breech position, in which case, those patients were delivered by c-section. Another study did show that a major risk factor for unplanned c-section in twin pregnancy is nulliparity and breech twin B.

While twin pregnancy is rare, so also is thrombocytopenia. While up to 12% of obstetric patients may have some degree of thrombocytopenia, only 1% meet the definition of moderate to severe thrombocytopenia (<100,000 x 10^6/L).  An anesthesiologist confronting a parturient with thrombocytopenia is most likely to be dealing with one of three main etiologies: 1) gestational thrombocytopenia 2) Immune thrombocytopenia (ITP) or 3) thrombocytopenia associated with hypertensive disorders of pregnancy (i.e. pre eclampsia; hemolysis, elevate liver enzymes, low platelet count [HELLP] syndrome).  It is estimated that of parturients who are diagnosed with Thrombocytopenia, 80% of these cases are a result of gestational thrombocytopenia (affects 5-11% of pregnant patients). Some important diagnostic clues include onset in the mid second semester to third semester, mild Thrombocytopenia (not usually less than 75K), no outward symptoms (easy bruising etc), and no prior history of Thrombocytopenia. The diagnosis can only be made by exclusion of other causes. The other main cause of Thrombocytopenia during pregnancy is that related to hypertensive disease of pregnancy.  This comprises 8 to 21% of patients with Thrombocytopenia during pregnancy.  In these cases platelet function can be impaired in addition to decreased in number.  The etiology of Thrombocytopenia in both of these conditions in unknown.


Unfortunately, given the low number of parturients presenting with thrombocytopenia who need neuraxial anesthesia, we do not have good numbers to determine the absolute risk (probability) of any one patient developing an epidural hematoma.  It should be noted, that thrombocytopenia refers simply to how many platelets are available, but tells us nothing of platelet function which may be normal, reduced or even increased.  Indeed, in pre eclampsia, platelet function is often impaired.  However, in general we know that the risk of epidural hematoma with neuraxial anesthesia is about 1:250,000 in all comers.  In a meta analysis reviewing 7509 neuraxial procedures, most epidural hematomas occurred in patients with platelet counts < 50,000 x 10^6/L. Of women with platelet counts < 100,000 x 10^6/L there were a total of 33 epidural hematomas, and 5 of these occurred in women with platelet counts between 44,000 and 91,000. However, ALL five of these had other ongoing issues [1 with AVM, 1 was coagulopathic on top of the low platelet count, 2 had HELLP syndrome, and 1 had full blown eclampsia).  

In another study, 1524 patients received neuraxial anesthesia with no epidural hematomas noted. The authors, however, estimated the upper limits of the 95% CI for the risk of spinal epidural hematoma stratified by platelet count.

  • 70K to 100K  ....0.2% risk
  • 50K to 69K   ....3% risk
  • <50K        .........11%
Unfortunately, it is not clear exactly how to use this information in clinical practice except to say that it appears risk is relatively low when platelets are above 70K.  


Thromboelastography (TEG) or rotational thromboelastometry (ROTEM) have been studied as it relates to neuraxial anesthesia with thrombocytopenia. These studies were able to show no spinal epidural hematomas in patients with thrombocytopenia AND normal parameters on the TEG or ROTEM. However, other studies in oncologic patients with thrombocytopenia have reported no correlation between TEG and ROTEM parameters and clinical bleeding unless platelet levels were below 50,000 x 10^6/L.

The platelet function analyzer (PFA)-100 test platelet function. Time to platelet plug formation is measured and labeled closure time (CT). An abnormal CT may be found in patients with counts <100,000 x 10^6/L, anemia, or significant qualitative platelet defects. However, at the end of the day, the consensus statement from the Society for Obstetric Anesthesia and Perinatology Interdisciplinary Consensus statement on Neuraxial Procedures in Obstetric Patients with thrombocytopenia can not recommend any of the above tests to determine the safety of neuraxial anesthesia.

Platelet transfusion:
A 1 unit apheresis transfusion is expected to raise the platelet count between 30,000 to 50,000 x 10^6/L, although the end result is often variable depending on the disease in question.  In particular, in HELLP or pre eclampsia, the end result may be much less than what was expected after transfusion.   In ITP, transfusion of platelets alone is likely ineffective and requires concomitant treatment with IVIG and/or corticosteroid therapy. It should be noted that platelet transfusions in platelet consumption disease such as ITP is short lived.

It is currently recommended [1] that the anesthesiologist confronting a parturient with thrombocytopenia should determine whether the patient has a known etiology for the thrombocytopenia.  In addition, it is critical to determine if there is a history of easy or prolonged bleeding with the thrombocytopenia.  In particular, the clinician should be confident that the etiology of the thrombocytopenia is not related to DIC or other highly morbid and evolving conditions.  If it is suspected or confirmed that this is a case of gestational, autoimmune (idiopathic) thrombocytopenia or related to confirmed diagnosis of hypertensive disorder of pregnancy, then verifying that a recent platelet count is above 70,000 x 10^6/L would allow the clinician to have a rather high confidence that neuraxial anesthesia is safe.  With a platelet count between 50K and 70K, a more careful cost benefit analysis should be carried out.  If the platelet count if less than 50K, the guidelines recommend avoiding neuraxial anesthesia.

The SOAP guidelines can be summarized in this algorithm which I found very helpful.





1. The Society for Obstetric Anesthesia and Perinatology Interdisciplinary Consensus Statement on Neuraxial Procedures in Obstetric Patients With Thrombocytopenia. A&A N. 132 2021 Pg 1531.


June 9, 2021

Waste anesthesia Gases

 The other day I arrived to our main hospital to relieve one of my partners who was working with several CRNAs.  One of the CRNAs had just arrived in the cath lab where we had been asked to anesthetize a patient for a cardiac catheterization procedure.  We induced general anesthesia with an ETT.  Shortly thereafter I was called to the room for an alarm with warning indicator of  " PEEP high. Blockage?,". I quickly determined that there was high pressure in the 3 Liter scavenging system bag and this was a result of not having the vacuum line connected to a central vacuum.  I thought it odd that the anesthesia machine had been placed in the cath lab without having been connected to the central vacuum for scavenging of waste anesthesia gases (WAGs). But it turns out there are no connections for vacuum in this particular room.


In the typical OR, the anesthesia machine has a scavenging system set up so that all WAGs are emitted into the atmosphere and do not contaminate the OR. Below is a figure with the basic outline of how this system would be set up.

Because all modern ORs are built the same most anesthesia providers take it for granted that WAGs will be scavenged.  


However, at times we are asked to provide anesthesia services outside of the OR setting.  In this case, the anesthesia tech for the hospital placed an anesthesia machine in a site that had no medical gas column therefore, no site for suction for the anesthesia suction hook up.  Therefore, the hose leading from the scavenging system meant for active suction of anesthetic gases from the machine to the environment was placed on the ground. The frequency of the build up of pressure could be decreased by using low flows (less than 1 L/m). However, this did not eliminate pressure build up.  Therefore, periodically we were forced to disconnect the circuit from the anesthesia machine as a manual vent of a pressure build up in the anesthesia.  The rationale for this will be discussed in more detail below.

The rationale for scavenging of WAGs comes from a number of studies on small concentrations of anesthetics on animals (predominantly rats) and humans.  

Nitrous Oxide has been shown to increase fetal death in rats and also to result in an increased rate of rib and vertebral defects.  In humans, dental assistants exposed to nitrous oxide in a setting without a scavenging system had a 59% decrease in fertility vs unexposed females.  Dental assistants working with nitrous oxide and using a scavenging system had no decrease in fertility rates. The exposure limit resulting in fertility problems was at least 5 hours per week of work with nitrous oxide. Likewise, similar findings were noted for the occurrence of spontaneous abortion in exposed workers (at least 3 hours of exposure per week) vs un exposed female dental assistants (working with a scavenging system). The relative risk of spontaneous abortion was 2.6.  In humans, there is no clear evidence for an increase rate of congenital abnormalities in females exposed to nitrous oxide. 

Halogenated agents:

Dental assistants  exposed to 8 hours per week of halogenated agents had an elevated rate of spontaneous abortion (19.1 per 100 pregnancies) vs dental assistants who worked with a scavenging system (8.1 per 100 pregnancies).  The wives a dentists with heavy exposure to halogenated agents also experienced spontaneous abortion at higher rates than non exposed females (10.2 vs 6.7 events per 100 pregnancies). A subsequent study found that spontaneous abortion was increased in exposed females and spouses of exposed males to halogenated anesthetics.  In this study, they are were able to determine that congenital abnormalities were also increased in female workers exposed as well as to spouses of male exposed workers.  

Unfortunately, due to the difficulties in conducting an RCT that is prospective, all of the data we have currently related to the harmful effects of anesthetics are retrospective in nature and therefore, not robust.  However, there are multiple different studies in both animals and humans plus the biologic plausibility of danger related to long term chronic exposure to anesthetics that lend to the credibility of the current evidence available to us.

In the above studies, it is important to note that the groups who suffered an increase in spontaneous abortion from anesthetic agents (presumably) were working in an environment where waste anesthetic gases were not scavenged, whereas, they were often times compared to workers who had access to scavenging of waste anesthetic gases.  Modern day anesthesia machines all come equipped with a scavenging system to dispose of all waste anesthetic gases to the environment.  It should be noted that ALL air flow (oxygen, air or nitrous) that is not consumed and metabolized by the patient will make its way into the scavenging system.  Therefore, much of the problem with waste anesthetic gases can be mitigated by  low flow anesthesia.  The scavenging system is made up of several parts with complicated names that are not terribly helpful in understanding their function.  

The above diagram highlights how the scavenging system is incorporated into the anesthesia machine.  It should be noted that when the anesthesia machine is in manual or bag ventilation mode, when the APL value "pop-off" valve is opened all the way to relieve "pressure" in the reservoir bag, the excess flow is directed into the scavenging system (which contains another reservoir bag [see figure above]).  Modern day OR's have active scavenging systems.  In other words, the excess flow from the anesthesia machine is hooked up to the hospital vacuum system (see figure above), and the excess gas is actively suctioned off.  If there is any obstruction to this vacuum system or its tubing, you will quickly develop a build up of pressure in the reservoir bag (see figure above). This will create a back up of pressure leading to the ventilator piston (setting off an alarm as indicated above) or to the reservoir bag on the anesthesia machine.  Opening the APL valve "pop-off valve", to relieve the reservoir bag will not help the problem at all since the "pop-off" valve simply leads directly to the scavenging system reservoir bag, the source of the high pressure. The scavenging interface on anesthesia machines come in two varieties.  An open interface system has no valves between the interface and the outside vent.  Therefore, this provides a safety mechanism in that there are no valves that can malfunction leading to pressure build up to the patient.  Our anesthesia machine, The Datex Ohmeda Asys CS2, has a scavenging interface that is a closed system, and therefore, relies on a positive pressure and negative pressure relief valve.  In our particular case, after removing the patient from the anesthesia ventilator, and opening the APL valve to vent excess pressure to no avail, it became evident that pressure was building up distal to the APL valve, which would be the scavenging system.   The scavenging interface allowed pressure to build up until 10 cmH2O, when the positive pressure valve vented excess pressure, but after 15 seconds of continuous pressure greater than 10 cmH2O, the "PEEP high" alarm is triggered on the machine.
It turns out that the Asys CS2 also has an option for an open scavenging interface system.  In this system, there would be no alarm because there would be no build up of pressure in the case of insufficienct extraction of WAGs. In these systems, they are designed so that extraction flow is greater than average waste gas flow, therefore, the hospital vacuum entrains OR air during anesthesia.  There is a 2L reservoir bag to hold WAGs should extraction flow fall below waste anesthesia gas flow for any amount of time.  Should this state continue until the reservoir bag is full, then WAGs would be vented to the OR proper.
In our situation, we needed to proceed without the ability to scavenge.We recognized the need to attempt to perfectly match the anesthesia gas flow to the patient's metabolic rate of oxygen (closed anesthesia system) or periodically vent excess pressure with disconnects of the patient from the anesthesia machine. 

While modern day ORs all have active scavenging systems, there are passive systems as well. A passive system would have tubing allowing the passive flow of the WAGs from the anesthesia machine into the environment or other collecting system.  All modern day ORs also must have high air exchange in order to reduce the concentration of anesthetic gases.  Despite active scavenging, waste anesthesia gases (WAGs) may escape from the machine during mask ventilation, or any time the patient is disconnected from the ventilator. Obviously, high flows should be avoided to reduce excess WAGs into the ambient room air during cases when the patient can be disconnected from the anesthesia.

Low flow anesthesia (usually considered to be 1 L/m of fresh gas flow as elaborated by Foldes in 1952) and minimal flow (@ 0.5L/m) was defined by virtue in 1972. These techniques can reduce WAGs dramatically. There are the additional advantages of cost savings on the volatile anesthetics, reduction of the drying affects of high fresh gas flows on mucous membranes and avoidance of cooling the patient, as well as the reduction of WAGs in the atmosphere. Open circuit anesthesia (FGF exceeds minute ventilation (Vm),  can be compared to closed circuit anesthesia where FGFs is set as low as the metabolic rate of the patient, and would, in theory, maximize the above benefits noted. There are three main contraindications to using minimal or closed circuit anesthesia.  These include patients acutely intoxicated with alcohol, patients in decompensated diabetic metabolic acidosis, and patients suffering from acute carbon monoxide poisoning.  The rationale is simply that the patients would be rebreathing the alcohol, acetones, or carbon monoxide respectively.  Desflurane is capable of being used in low flow anesthesia with little controversy. Sevoflurane has been shown to produce compound A at low flows which caused acute tubular necrosis in rats at concentrations greater than 250 ppm.  At FGFs of 1 L/min compound A is usually fond to be around 15 ppm in clinical anesthesia but the amount of compound A produced is a function of the concentration of sevoflurane delivered, the duration of exposure to the absorbent, lower FGFs, the temperature and desiccated absorbents. Since the reaction that eliminates CO2 is an exothermic reaction, as the amount of CO2 absorbed increases temperature increases linearly producing greater degradation of sevoflurane to compound A. Therefore, in spontaneously breathing patients with significant hypercarbia, the risk of elevated compound A is elevated.  Howeve, recent evidence suggests that compound A is not as clinically relevant with soda lime absorbers vs baralyme [2].   Furthermore, the studies raising concerns initially, were invalidated  due to the marked difference between rat and human renal biochemistry. Nevertheless,  The FDA issued a lower limit FGF rate when using  sevoflurane at 2 L/m when using sevoflurane for  greater than 2 MACs hours. Typically, to be safe, clinicians set FGFs to at least 2 L/m when using sevoflurane.  However, this doubles the cost and production of WAGs when compared to a setting of 1 L/m.   I have created a quick calculator to help a clinician determine how long the anesthetic may continue with sevoflurane at  low flow (1 L/min) before exceeding the FDA recommendation of 2 MAC hours  (see calculator here).  It should be noted that the studies the FDA relied upon to publish a warning label on sevoflurane were problematic and it is not clear at all that there is significant real clinical risk from compound A to humans at low FGFs. In fact, The Brigham and Women’s Hospital Anesthesiology Clinical Practice Committee approved the use of sevoflurane at any fresh gas flow when CO2 absorbents are used that limit the added strong base. The justification was that these products permit safe, effective and planet-friendly use of low-flow or closed-circuit delivery of anesthetic agents. Similarly, the University of California, San Francisco implemented a fresh gas flow alert within the electronic medical record that notifies providers if their flows exceed 1 liter per minute and does not require a minimum fresh gas flow for sevoflurane. 

Regulatory bodies:
OSHA does not mandate any particular scavenging system for WAGs.  However, I did find this reference related to Joint commission where it states that they mandate scavenging be used when WAGs could be a problem (i.e. they are used for anesthesia). [1]  In 1977, the national institute of safety and health (NIOSH) made a recommendation that workers should not be exposed to a greater than eight hour time weighted average of 2 ppm of halogenated agents. The limit is only 0.5 ppm if nitrous oxide is being used.  The limit for nitrous oxide is eight hours time weighted average of 25 ppm.  Obviously, the ability to make these calculations on the fly and track it is not done in the real world and would be expensive and difficult requiring the workers wear a badge of some sort that could record the exposure and then maintain that reading.  To me, the message is that there is really little tolerance for any exposure and a scavenging system is mandatory for inhalation anesthesia.

The scavenging system on modern anesthesia machines actively emits anesthetics into the atmosphere. Therefore, there is a plausible concern of the effects of these hydrofluorocarbons in the atmosphere. Indeed, anesthetic gases are recognized as green house gases (GHGs).  The US health care sector is responsible for about 10% of US GHG emissions.  If the US healthcare sector were a country, it would rank 13th  in the world for GHG emissions, ahead of the entire United Kingdom.  Kaiser Permanente, one of the nation’s largest non-governmental health care systems, has a robust sustainability program. Anesthetic gases account for 3% of the organization’s greenhouse gas emissions – over half of which was from desflurane [3].  In 2014, WAGs stood at the equivalent of 3 million tons of carbon dioxide. Greenhouse Gases (GHGs) differ in their abilities to trap heat. The effect of this heat trapping over a 100-year period is described using a scale called the global warming potential over 100 years (GWP100). This allows a direct comparison a variety of different gases using CO2 as a baseline with a value of 1.

GWP100 for several anesthetics
CO2    ......................1
Methane..................30
SEVO......................130
N2O  ........................298
ISO    ......................510
DES  ......................2540

SEVO is much lower than DES in part because it remains in the atmosphere for 1.1 years vs. 14 years for Desflurane.  Nitrous remains in the atmosphere for about 150 years making its GWP100  fairly high.

To use another analogy to better put in perspective the GHG effect of anesthetics vs CO2 it is helpful to compare a typical anesthetic to driving a car some distance.  As an example, a two hour anesthetic with desflurane with fresh gas flow (FGF) of 1 L/min using a 1 MAC setting would be the equivalent of driving a car 378 miles (from Los Angeles to  Phoenix).  The same anesthetic with sevoflurane but at double the FGF would be the equivalent of driving about 16 miles. see chart below:

Table. One hour of anesthetic is like driving a car [how many?] miles.a
Dose (1-MAC-hr)Sevoflurane 2.2%Isoflurane 1.2%Desflurane 6.7%N2Ob 0.6 MAC-hour
0.5 L/min49329
1.0 L/min4718957
2.0 L/min815378112
5.0 L/min1938939282
10.0 L/min38741,876564
a Assumes EPA 2012 fuel efficiency average of 23.9 miles per gallon.
b Because N2O cannot be delivered at 100%, the more typical percentage of 60% is used. In combination, 0.6 MAC-hour of N2O would be added to 0.4 MAC-hour of a volatile.
EPA, Environmental Protection Agency; MAC, minimal alveolar concentration; N2O, nitrous oxide




After the choice of anesthetic, the FGF used is the next most important determinant of the carbon footprint of a typical anesthetic. Any anesthetic with FGF beyond the metabolic needs and system requirements will be vented into the atmosphere as described earlier via the scavenging system. Thus, if you double the FGF of sevoflurane from 1 l/m to 2 l/m, the output of CO2 equivalent GHG is doubled for sevoflurane and for desflurane. Adding N2O to the anesthetic, but keeping the FGFs equivalent, will increase the CO2 equivalent emissions by 20 times. Therefore, the ability to decrease the concentration of the halogenated agent because of the N2O does not come close to compensating. Furthermore, N2O is known to deplete the ozone layer in the atmosphere.

However, to put this all into perspective, an equivalent of 6% of global carbon dioxide emissions result from nitrous oxide, where 1% of these are medicinal. Furthermore, as a waste anesthetic gas, N2O contributes roughly 0.1% of the whole GHG.  In addition, N2O contributes by far, the largest amount to GHG when compared to all waste anesthetic gases as the consumption values of N2O far exceed those of other anesthetic gases.

From a GHG perspective the perfect inhalation anesthetic would be Xenon which acts via inhibition of calcium pumps in cell membranes which may increase intraneuronal calcium concentrations altering excitability. Xenon also inhibits NMDA receptors, as well as nicotinic acetylcholine receptors.  Other beneficial characteristics of Xenon include:
  • non-flammable and non-explosive
  • Rapid onset/offset (partition co-efficient of 0.12 (lowest of all anesthetics)
  • Zero metabolism, low toxicity, and devoid of teratogenicity.
  • Produces high regional blood flow in brain, liver, kidney and intestine.
  • Neuroprotective
  • Lacks cardiovascular depression
So why doesn't Xenon replace all current inhalation anesthetics?  It costs $10.00/Liter, far more than current inhalation agents.

In summary, when performing anesthesia outside of the regular OR, the anesthesia provider will be forced to determine if WAGs are scavenged as it is likely this component has been forgotten.  WAGs have a real, although small, negative health effect over time on exposed personnel.  Regulatory bodies demand that WAGs be eliminated in the anesthetizing location as best as possible which requires scavenging.  Anesthesia technique, utilizing low FGFs, etc can reduced exposure of the OR worker as well as mitigate to some degree contaminants into the environment.

2. Kharasch ED, Powers KM, Artru AA. Comparison of Amsorb, Sodalime, Baralyme degradation of volatile anesthetics and formation of carbon monoxide and compound in swine in vivoAnesthesiology. 2002;96:173–82