Case Reports in Anesthesia

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

May 18, 2020

severe bronchospasm after induction in obese female

Sunday afternoon the friendly GI doc boarded a case for an urgent ERCP in a 31 year old female with choledokolithiasis.  She had elevated liver enzymes and he was concerned that she might develop ascending cholingitis.  The patient had hypothyroidism and was morbidly obese with a weight of apporoximately 320 lbs and was 5'3". We proceeded to the OR after 2 mg versed, 100 mcg fentanyl and 4 mg decadron were given as a premed.  In the OR after monitors were applied, pre oxygenation in the reverse T - burg position with HOB up at 30 degrees was accomplished.  Induction with 150 mg of propofol and succinylcholine (100mg) was used.  Intubation was easy grade I view.  However, She immediately desaturated (less than 60 seconds). Manual ventilation was begun to expand lung units, and sevoflurane was begun and saturations slowly climbed to the high 90's.  Within 4 to 5 minutes, the patient began moving slightly. I immediately went to increase the sevoflurane, but noticed at this point that the vaporizer was completely empty.  Unfortunately, the machine only allowed one vaporizer at a time to be inserted into the port. Therefore, I had to remove the sevo cartridge and insert the cartridge with desflurane.  The patient was now starting to move and cough, causing her to desaturate again.  I overpressurized the desflurane to quickly deepen the anesthetic to prevent further coughing and bucking on the ETT.  The patient, again desaturated significantly (down into the 60's). With careful and aggressive manual ventilation to expand all alveoli units, her sats slowly started to climb and the desflurane was able to be delivered.  In an attempt to quickly deepen the anesthesia, I had turned the desflurane up to 10%.  After getting her sats back up into the 90's, I switched again to machine ventilation with pressure control of 29 and PEEP of 9 mmHg.  However, within a short period, her sats began to fall again.  I decreased the desflurane to 6% and once again took over manual ventilation.  I perceived that indeed her compliance was very poor.  I quickly verified once again that her ETT was not in too deep (i.e. right main stemmed), and that there were no kinks in the ETT.  I also gave 40 mg of rocuronium to ensure that she wasn't fighting the ventilator and rule out any chest wall contribution to poor compliance. With careful high pressure ventilation I was able to achieve large tidal volumes (not achievable with the anesthesia machine despite high pressure settings in pressure control ventilation).  Her saturations again trailed down into the 60's.  At this time the ERCP was underway, and the endo team was particularly involved with the procedure. The anesthesia tech had left for the day (I'm not sure why). I suspected bronchospasm at this point (previously thinking I was dealing with atelectisis with shunt due to morbid obesity).  Therefore, I asked for help in filling the vaporizer.  During this time I was forced to put her back on the ventilator with saturations in the 80's.  I quickly filled the sevo vaporizer, and switched the desflurane cartridge for sevoflurane. I dialed in a  4% concentration with high FGF (i.e. 5 l/m).  After about five minutes, her compliance began to improve, her saturations slowly improved for the remainder of the case.  Now that I could rely on mechanical ventilation, I was free to grab some albuterol and hook up a make shift nebulizer treatment via the ETT and ventilator which required some creative hookups to achieve success.  The case lasted about 50 min. At the end of the case, compliance was pretty near normal levels with normal saturation's.  However, the patient was still weak from the very large dose of rocuronium given to ensure improved compliance. Given that she only had one twitch and the Concern for airway patency, I administered 200 mg suggamadex.  I followed this dose with a subsequent dose of 100 mg to achieve full reversal in about 3 minutes.  The patient went to PACU extubated on face mask O2 and saturations at 100%.

This case highlights the interplay of obesity, asthma (bronchospasm/reactive airway disease) and desflurane.
Obesity has reached epidemic proportions in the US.  Super obese patients require surgery for a variety of problems and can present unique problems for the anesthesia team.  In this case, the patient reported no significant past medical history with the exception of hypothyroidism.  However, severe hypoxemia was encountered almost immediately after induction, which was exacerbated by significant bronchospasm likely brought on by high (overpressurization) concentrations of desflurane.

Pathophysiology of the obese state

Excess adipose tissue is associated with the production of various proinflammatory cytokines, including tumor necrosis factor-α (TNF-α), interleukin-1-β (IL-1β), and interleukin-6 (IL-6). TNF-α plays a critical role in the inflammatory response of the immune system as well as in the apoptosis of adipose cells, lipid metabolism, hepatic lipogenesis, and the induction of oxidative stress. Increased levels of TNF-α promote a response via the release of IL-6, another proinflammatory molecule, and the reduction of levels of anti-inflammatory cytokines such as adiponectin. TNF-α also increases the interaction of electrons with oxygen, generating superoxide anions. TNF-α levels are elevated in obese individuals and decrease with weight loss [1]. Furthermore, Adipose tissue is a source of several bioactive adipokines, including leptin, adiponectin, visfatin, resistin, apelin, and type I plasminogen activation inhibitor (PAI-I). These adipokines are directly associated with physiological and pathological processes involving oxidative stress  [2].  Rasslan et al. [3] observed that adipose tissue is an endocrine and paracrine organ that produces many cytokines and bioactive mediators, resulting in a pro-inflammatory state that may be associated with pulmonary hypoplasia, atopy, hyper reactive bronchi, and increased risk of asthma in obese individuals. Leptin is one hormone elevated in the obese state, likely related to leptin resistance and consequent overproduction.   Leptin crosses the blood brain barrier and serves as an afferent signal, originating from the adipose tissue, engaging distinct hypothalamic effector pathways to suppress appetite and augment energy expenditure. Therefore, leptin is an important negative feedback loop in controlling appetite to prevent obesity. Leptin resistance has been shown to enhance  parasympathetic tone which increases airway reactivity and obesity associated asthma [8]. In addition, hyperleptinemia was proposed to be a crucial factor leading to respiratory failure in leptin-resistant obese subjects [9].  Meta-analyses have further implicated a positive relationship between serum leptin and the risk of asthma. Of note, the link with obesity and airway hyper responsiveness is much stronger in females than males. Furthermore, it has been shown that Leptin expression is inhibited by testosterone, whereas it is increased by ovarian sex steroids and therefore, leptin is higher in females than age and body mass index (BMI) matched males. Of note, leptin also plays a role in central respiratory function.  Injection of leptin into the nucleus of the tractuss solitarius increases minute ventilation in addition to enhanced bioelectrical activity of the respiratory muscles.  This seems to indicate that in obesity with leptin resistance, patients will be at much higher risk for OSA partially related to the inability of the brain to react to high leptin levels. In obese patients, hyperleptinemia is associated with a reduction in respiratory drive and hypercapnic response, irrespective of anthropometric measurements while circulating leptin is a predictor for the presence of hypercapnia.  Furthermore, as discussed above, high leptin levels result in the production of a number of cytokines that induce inflammation. Administration of leptin to wild-type mice enhances O3-induced airway inflammation (in other words, airways are hyper reactive in mice who are given exogenous leptin).  In summary, while the evidence relating leptin levels to lung and respiratory pathology is mixed, there seems to be a general preponderance of studies linking obesity, leptin resistance (i.e. elevated leptin levels) and hyper responsive airways. 






However, the situation is yet more complicated.  It is known that obese women have higher levels of estrogen than their non obese counterparts. Elevated estrogen is also known to be an independent risk factor for asthma.  Furthermore, adiponectin seems to have the exact opposite effect as leptin in the body, i.e. inhibits the production of IL-6, TNA-alpha and other pro inflammatory mediators.  Studies have noted that adiponectin levels are reduced in asthma  and reduced in subjects with low lung function.  However, this was true only in women. Low adiponectin levels are found in obese patients. 

Therefore, the obese state creates altered hormonal levels from the non obese state that have a pro inflammatory effect and promote hyper responsive airways.


In addtion to the above described endocrine pathology of obesity, Mafort et al. evaluated 30 patients and showed that the primary change in lung volume was reduced end respiratory volume.  In the morbidly obese, FVC and FEV1 were both reduced.  However, obesity has been associated with a higher incidence, prevalence and severity of asthma and with altered pulmonary function, poor treatment response, and high morbidity.  The increased incidence is correlated with BMI in that there is a 35% increase in the risk of asthma with each 3 unit increase in BMI. Further derangements of lung function in obese individuals have been identified. Radial traction of lung parenchymal attachments around the airways is attenuated at low lung volumes contributing to airway collapse. Breathing at low lung volume is a hallmark of respiration in morbid obesity.  When an obese patient goes from standing to supine, there is no further decrease in FRC and expiratory reserve volume (contrary to what is seen in lean people).  But, Airway resistance increases with decreased expiratory flow. As intrinsic (or auto) PEEP develops, work of breathing (WOB) increases and the supine obese patient develops a mixed respiratory pathology of restrictive and obstructive etiology. In the supine obese patient oxygenation is particularly affected by breathing at low lung volumes where expiratory reserve volume approaches residual volume. A decreased expiratory capacity seems to be the primary cause of decreased ventilation/perfusion ratios causing significant and rapid hypoxemia after induction of anesthesia. Therefore, pre oxygenation with pressure support and PEEP in a head up (at least 25 degrees), can increase safe apnea time. After intubation, recruitment maneuvers with titrated PEEP can optimize oxygenation. Obese patients are far more susceptible to ventilator induced lung injury (VILI) due to the potential for high driving pressures to ensure adequate ventilation. The dual concepts of static stress and dynamic strain on the lungs come into play both adding to the risk of VILI.  By titrating PEEP appropriately, both of these can be mitigated to a degree.  Large PEEP values (at least 12 cmH20) may be needed, however.  As the degree of end expiratory lung pressures increase, the right ventricle will be exposed to increased afterload.  However, at very low lung volumes, right afterload is also increased due to collapsed vasculature.  Therefore, the obese patient will need to be well hydrated to counter act the potential negative CV effects of increased levels of PEEP.


There is evidence that metabolic syndrome (obesity, insulin resistance, atherogenic dyslipidemia and hypertension), is a key contributor to worsening lung function. Metabolic syndrome shares a great deal of pathologic features with polycystic ovary syndrome.  This 31 y/o female also had PCOS.  See graph: 


In the end, airway hyperesponsiveness, reduced lung volume, air trapping, auto peep, increased inflammation, and increased work of breathing all contribute to reduced pulmonary reserve in obese individuals with worsening pathology at greater BMIs. Airway hyperresponsiveness was found in a study of  obese patients undergoing laparoscopic surgery.  In this study, obese patients had an incidence of bronchospasm of 12% vs. 0% in non obese patients.  

The anatomy of airway hyper responsiveness as experienced in this case of acute intraoperative bronchospasm is demonstrated with the following graphic.




While obesity does increase airway responsiveness, anesthetic vapors also effect airway responsiveness.  Back in 1997, Rooke at al. [5] showed that Sevoflurane reduced airway resistance after intubation  more than Halothane or Isoflurane.  In 2000, Desflurane was compared head to head with Sevoflurane to determine airway resistance after intubation, and shown to increase airway resistance while Sevoflurane was able to reduce airway resistance [6]. (see graphic)


It should be noted, that the majority of the increase in degree of airway resistance in patients receiving Desflurane were in those who were smokers. Even still, non smoking patients who received Desflurane saw no decrease in airway resistance like those who received Sevoflurane.  In 2008, a study [7] in pediatric patients comparing Desflurane to Sevoflurane in normal patients and in those with airway senstivities was able to show that Sevoflurane decreased airway resistance slightly in both groups, while Desflurane increased airway resistance. (graphic)


light bar is normal patient, and the dark bar are patients with airway sensitivity.


More recently, a case series in the PICU was able to show that in six children with life threatening asthma exacerbations, Sevoflurane successfully relieved bronchospasm and all children made improvement except one who was later diagnosed with ARDS and required NO.  Consequently, while desflurane has a superior recovery profile vs Sevoflurane in obese patients due to its very low solubility co efficient in blood and fat, in some patients, the potential for increased airway resistance may present problems.  In my patient, who was super obese, a severe bronchospasm was elicited after introduction of Desflurane with overpressurization.  Sevoflurane was able to break this bronchospasm successfully.  The patient was required to return for a lap chole three days after her ERCP.  The team used sevoflurane.  I arrived towards the end of the case to relieve the provider who had started the case.  On the hand over report I was told that she had saturated in the high 80's for much of the case, but this improved to mid 90's after the evacuation of the pneumoperitoneum.  She was maintained on Sevoflurane, and upon emergence and transfer to the PACU she did well although she required oxygen.  On POD #2, she required an additional ERCP due to more stones found in the duct.  After intubation, recruitment breaths were used, and she was placed on 9 cmH20 of PEEP with pressure control ventilation of 30 cm H20.  Sevoflurance at 2.4% was used.  She did not experience any evidence of bronchospasm, and saturations were maintained at 98% on Fio2 of 0.85.  She was extubated at the end of the case and went to PACU without incident. 







1. Möller K, Ostermann AI, Rund K, Thoms S, Blume C, Stahl F, et al. Acids. 2016;106:39–49.

2. Marseglia L, Manti S, D’Angelo G, Nicotera A, Parisi E, Di Rosa G, et al.  Int J Mol Sci. 2014;16:378–400.
3. Rasslan Z, Stirbulov R, Lima CA, Saad JR. Lung function and obesity. Rev Bras Clínica Médica. 2009;7:36–9.
4. Grassi L, Kacmarek R, Berra L.  Anesthesiology. 2020;132:1246-56.
5. Rooke GA, Choi J-H, Bishop MJ: . anesthesiology 1997; 86:1294–9
6. Goff MJ, et al. Anesthesiology  2000, Vol.93, 404-408
7. von Ungern-Sternberg BS, Saudan S, Petek F. et al. Anesthesiology  2008, Vol.108, 216-224
8. Arteaga-Solis, E. et al.  Cell Metab. 2013;17, 35–48 
9. Phipps, P. R., Starritt, E., Caterson, I. & Grunstein, R. R.  Thorax 57, 75–76 (2002).


May 1, 2020

ramping up elective cases as COVID-19 ramps up as well

As the Anesthesia Chair at a small community hospital I have been involved in helping to make decisions about how to ramp up elective cases as Government Abbot's decision to cancel elective cases comes to an end.  We are scheduled to begin regular cases on May 1st as we certified that we would comply with all of the requirements in order to do so.

I work for a large anesthesia group that has communicated recommendations on how we should protect ourselves as we ramp up.  Some of the recommendations have caused me to think about the rationale behind them a little more in depth to see whether they may apply to our community hospital.

The current recommendation in general is that all patients should be tested using RT PCR as well as tested for IgM/IgG antibodies.  The idea behind this is to reduce the chance of transmission of infection from an asymptomatic patient who has COVID-19 and also reduce the burden of PPE burden.  The general recommendation however, continues on that it is recommended in asymptomatic patients who test negative via both serology and PCR (also known as molecular testing) that providers who intubate/place an LMA for surgery should don an N95 mask and gloves per the usual method as we now do for untested patients.  Furthermore, it is still recommended to don maximal barrier protection (i.e. face shield, double gloves, gown, n95 or PAPR) in cases on the respiratory tract such as bronchoscopies, ent etc even if the patient has tested negative using both PCR and serology.

The argument put forward for this recommendation relates to the sensitivity of the two tests.  Our gurus have quoted a sensitivity of 98.6 % when the two tests are done together.  However, I do not believe this gives us a full picture of the actual risk to any given patient under our care.  First of all, as clinicians in practice, we really don't care about the sensitivity of any test except to use it in the calculation of the negative predictive value of our test.  The negative predictive value relates to Baye's rule where the pretest probability of the disease is considered.  In this case, we are concerned with asymptomatic patients, no known contact with a COVID-19 positive patient living in our local community who has not traveled or taken excessive risk related to work environment etc.  The pretest probability in this case is simply the current prevalence of disease in the community.  Unfortunately, we don't really know the current prevalence in real time because it is changing everyday.  Fortunately, my county publishes daily the prevalence in all of the individual surrounding communities.   Currently, the prevalence  is 1%.  This can be doubled (to account for positive patients who have not been tested). After considering the prevalence, the negative predictive value can change dramatically given the same sensitivity.

Understanding why we do what we do in the OR to prevent transmission of infection is important and should be based on rational science underlying infectious disease.  The first principal of infectivity of any pathogen has to do with inoculum: A larger inoculum of pathogen is more likely to cause an infection than a lower inoculum.  The second principal considers how virulent the pathogen is.
The reason that Sars CoV-2 has been so easily transmitted is tied to the ability of the host's viral load to reach near peak levels prior to the symptom onset.  (See graph)


From ASA townhall
Therefore, SARS-CoV-2 is very contagious largely because asymptotic individuals can have very high viral loads allowing them to deliver a large inoculum without realizing it.  Therefore, the ability to detect viral burden in a patient without symptoms can aid us in determining how to handle the person in question.  Unfortunately, as per the slide above, PCR will only detect virus (turn positive) if the viral load is relatively high AND the test is done correctly.  When the specimen is collected in appropriately, or the viral load is low ( i.e. it's day one of the infection), then the test will indicate negative while the patient is really infected.  This results in published sensitivities of anywhere from 60% to 90%.  The important point to keep in mind about sensitivity and specificity is that they are characteristics of the test, and have nothing to say about the population the test is used in. (Sensitivity = Tp/Tp+Fn)   We really need to calculate the negative predictive value of our negative result. For this we need to know the prevalence in our community (or the community in which the patient resides and spends most of their time).  In my community, the current prevalence is less than 1%, but I'm going to assume 2% for a margin of safety and to presume a higher real prevalence due to lack of testing of all individuals in the community.  So lets go through what we are looking at with negative predictive value: 
The above graphic illustrates our example and shows the relevant formulas to calculate the relevant results.  In our hypothetic case, if we assume that the PCR test has a sensitivity of 85% and we assume a prevalence of 2%, the negative test result tells us that the the actual chance of you actually encountering a patient who is infected  is three patients for every 1,000 you care for. Of course, that is still not the whole story.  You also have to consider the risk for you personally.  For example, are you a healthy 35 year old female? Are you a 60 year male on corticosteroids for a chronic disease, with hypertension, DM and obesity?  The 35 year female who is infected with SARS-CoV-2 is likely to have a very different clinical course than the 60 year male as described. It should be noted that males who acquire SARS-CoV-2 tend to have a much higher mortality. It could be argued however, that wearing an N95 mask for intubation and extubation is still reasonable.  It could be argued that guidance to have OR staff stay clear of the patient during intubation and extubation is also reasonable.  However, some facilities have taken a very conservative stance and are demanding that after intubation or extubation, a full 20 minutes should pass prior to allowing any OR staff to enter the room. I will touch on this policy at the end of this article.  additional cost was invested into having the patient arrive 72 hours prior to scheduled surgery to have a swab performed for PCR testing.  (The test should be done at least 72 hours prior to surgery because of the above graph showing how patients may be in the early phase of infection resulting in low viral shedding and thus a negative PCR test). This is where the prevalence in your community plays a role.  If the prevalence is 15% in the community and the patient is known to have a known COVID-19 contact, the NPV is different: see graph:
(prevalence 20% is due to known positive contact: best guess)

 However, at this point perhaps it is reasonable to move forward with the more conservative approach.  What would you do?  Would you don full PPE (i.e. double glove, PAPR throughout entire case, gown entire case, videolargyngoscope for intubation)?  I personally would be comfortable using an N95 for intubation and extubation with eye shield and gloves. But during the remainder of the case I would not don an N95 if the case was not considered to be aerosolize generating.

Fortunately, I live in an area with a known prevalence of less than 1%. Obviously, there are probably a fair number of asymptomatic individuals who have the virus and could show up for surgery.  The other side of the coin is to consider that there is a cost to using full scale PPE, the resource is limited, there are few surgeries that are elective to the point that they are never needed (i.e. eventually the patient needs their surgery), and the longer we go without providing services for elective surgeries, the larger the back log of cases will be.  Therefore, ramping up will require an intelligent approach utilizing a full understanding of the true risk associated with caring for asymptomatic patients.

At my small private hospital the intention is  to provide both molecular (PCR) testing and serology (antibody) testing for all patients.  PCR testing is recommended to be done about 48 to 72 hours prior to surgery.  This is because the test will be negative in an infected patient very early on in infection due to low viral load. Please see the above graph showing how the viral load ramps up over 5 days or so.  Serology testing is recommended to be done just prior to surgery with enough time to get results.  This is because it can take several days to weeks for IgM antibodies to appear and up to four weeks for IgG antibodies to appear. A recent study was able to show that when PCR alone was used the sensitivity of test was 51.9%, but when adding serology (IgM) testing into the mix, the sensitivity improved dramatically (98.6%). So lets look at the graph below with this new sensitivity and we will assume a very conservative prevalence of 5%.
 In raw numbers, I would have to care for 1,000 patients before I ran into one patient who was a false negative. Some practices are busy enough that this isn't good enough.  Therefore, the cost benefit of depleting PPE for every case becomes questionable. I personally do not think it unreasonable to approach a healthy patient coming from a low prevalence area to this particular facility with routine universal precautions if they are negative for SARS-CoV-2 after both  PCR test (done 72 hrs prior to surgery) and a serology test done no more than 24 hours prior to surgery.  The critical piece to this is to have access to updated prevalence data from the community from which the patient resides and to verify that the patient has not traveled in the last 14 days nor had contact with others who might have traveled or had symptoms similar to COVID-19.  This could be accomplished prior to surgery by simply asking the patient a few questions.

In the real world different facilities are currently planning different testing patters.  In my area, a large nationwide hospital chain is not requiring ANY test prior to elective surgery in asymptomatic patients with no known risk factors.  They are asking the surgeons to request the test (PCR) and then it will be done. As an example, the Mayo clinic is performing dual testing (PCR/serology) on all asymptomatic patients 48 hours prior to surgery. However, vanderbilt is using just the PCR test. This is also true of other major institutions.  Cost is likely to be a major factor in making this decision. Each test can be around $100.00.  In addition, different facilities are requiring different levels of PPE depending on the test results.  Again, Vanderbilt who is performing the PCR nasal swab, will not require N95 if the patient tests negative.  UCSF (also using single molecular testing) will allow the provider to opt out of N95, but allows the provider to choose if the patient tests negative.  Mayo, (dual testing), still requires N95 regardless of test results. The takeaway, we still really don't know what the right answer is.  However, I believe the pre test probability (baye's rule) should be a large factor in determining whether you believe the test.  In a patient who has been living with a COVID-19 patient in close quarters, and comes for elective surgery, testing would allow you to decide to proceed with surgery should it be negative, but the NPV of the test  would likely be low. In that case, the testing would not impact my decision to use enhanced PPE. 

There are also questions related to what actually results in aerosolization of  SARS-CoV-2.  The current recommendations for PPE during intubation and extubation are largely based on the experience of HCW during the SARS-CoV-1 outbreak.  During that outbreak, HCW doing intubations had a higher rate of infection than others. Other data comes form the recent experience in Wuhan.  For example, there is anecdotal evidence of cases of contracting SARS-CoV-2 after an arduous intubation where nasal intubation was ultimately required.  In this case, several HCWs contracted SARS-CoV-2 despite the use of N95 masks.  However, the anesthesiologist, who was utilizing a PAPR, did not contract the disease.  Other anecdotes are similar, for example, all HCWs contracted SARS-CoV-2 after transphenoidal puitary surgery except the anesthesiologist who again was using a PAPR.    The takeaway for me is that first, there is a lot we don't know right now about how different procedures may lead to different aerosolized viral particles.  Second, a one size fits all approach is not the best.  Thirdly, as far as I can tell, at least I could not find any published papers, where someone measure the amount of aerosolized particles after an intubation.  It is clear that difficult and prolonged airway manipulation will lead to higher risk (i.e. prolonged ongoing surgery using a high speed drill (Transphenoidal pituitary surgery).  However, gently placing a blade into the mouth, with careful ETT placement may cause very little in the way of a viral plume.  Extubation can be much more dangerous.  The main documentary evidence leading to the recommendation of N95's indicates that HCW doing intubations were more likely to contract SARS CoV-1, but did not specify whether the exposure might have occurred during extubation.  There is some data that the virus can be aerosolized but the study was unable to determine the amount of viable virus in the aerosolized form only that in some cases viral particles may remain viable for several hours in aerosol form.  This same study also found that the floor is the most contaminated surface due to droplets migrating to the ground via gravity. The study seemed to indicate that the quantity of viable virus decreases significantly with distance from the source.  
Many facilities want to preserve PPE. In a drastic maneuver to do this, they are demanding that all staff not required for intubation/extubation remain out of the OR for varying amounts of time. The rational is by allowing the viral particles to clear via air exchange, the OR crew may enter and perform the surgery without enhanced PPE. It is not clear to me whether the decrease in throughput, expense of staff and OR for additional time, risk to patient who must remain under anesthesia for a longer period and other factors may outweigh the benefit. Or would dual testing be cheaper and do away with this requirement for negative patients? Furthermore, the wait times vary from institution to institution and the prescribed wait time seems arbitrary.  It is not clear if the times are based on good data, or whether a best guess. The CDC published the following related to this topic:

ACH Time (mins.) required for removal
99% efficiency

10+28
12+23
ACH-air changes per hour (dependent upon each facilities air conditioning units)

t2 – t1 = – [ln (C2 / C1) / (Q / V)] X 60 

The above equation is used to calculate the time listed above and is highly dependent on the volume of the room. The C relates to the viral concentration.  This is totally unknown and will be much higher for certain intubations than others.  I would also argue, that the initial viral load will be much higher after extubation than intubation.

In summary,  SARS-CoV-2 is a novel virus that has an Ro of around 3 or higher.  This indicates that it is highly contagious.  Current tests are not uniformly highly sensitive (i.e. PCR), but dual testing patients provides sensitivity of 98.6%.  In low prevalence areas, the NPV can be as as high as 99.9% after dual testing.  For providers in low prevalence areas providing care to small to moderate numbers of patients, forgoing enhanced PPE during cases where the patient was negative on two different tests (rt PCR and serology) may be reasonable.  The decision to preserve PPE may also depend on the type of case (i.e. an airway case with prolonged manipulation of the airway with high impact equipment).  The requirement for requiring staff to wait outside the OR during intubation and extubation likewise could depend on other factors as well? Local prevalence, what kind of testing was done, was the intubation difficult or very smooth and non traumatic, did the patient have any known risk factors to raise your suspicion etc.  Furthermore, N95's are susceptible to failure in certain high viral load environments.  However, PAPRs are total overkill for routine non airway surgeries in COVID-19 negative patients or unknown but low risk patients.  
Please feel free to use the below link to a web based calculator to help you individualize your care. Please note that patients who have SARS-CoV-2 contact, or symptoms (such as fever, cough, SOB, dyguesia, anosmia, headache) should be assumed to be positive no matter what the test states when determining whether to use enhanced PPE. This tool is related to asymptomatic patients with no known contact with a SARS-CoV-2 positive patient.







April 20, 2020

HIV + patient for urgent c/s


A 26 year old female diagnosed with HIV for several years was urgently brought to the OR for a c/s for NRFHT.  The patient was being treated by quadruple anti viral therapy for her HIV. She was also on bactrim presumably as a prophylactic against PCP +/- toxoplasmosis.  After successful spinal anesthesia, the patient was laid down and oxygen applied.  I discarded of all sharps, and then went to dispose of the remaining packaging.  As I did so, my index finger received a superficial puncture from a needle that had not been visible in the remaining packaging.  I discovered that it was the needle used for the local anesthetic injection prior to the spinal injection. The cap had fallen off exposing the needle.

HIV is a Lentivirus that belongs to a group of retroviruses. Reverse transcriptase is an enzyme that  enables retroviruses such as HIV to transcribe their own RNA into DNA. This DNA can then been incorporated into the host genome to produce large quantities of new HIV RNA. HIV attacks the cells containing antigens CD4 (T-helper lymphocytes and macrophages) on their surface and then destroys them, which leads to immunodeficiency, increased incidence of opportunistic infections, and malignancies.   


According to the International Health Care Worker Safety Center (IHCWSC), approximately 295,000 hospital-based healthcare workers experience occupational percutaneous injuries annually. Other studies put the risk of needle stick injuries at 83% annually. There are more than 20 blood borne pathogens that might be transmitted from a contaminated sharp, but the ones most  commonly affecting health care workers (HCW) are HCV, HBV, and HIV.


List of potential pathogens transmitted after needle stick injury

  • Human T lymphotrophic retroviruses (HTLV I and II)
  • Hepatitis D virus (HDV or delta agent, which is activated in the presence of HBV)
  • Hepatitis G virus (GB virus or GBV-C)
  • Cytomegalovirus (CMV)
  • Epstein-Barr virus (EBV)
  • Parvovirus B19
  • Transfusion-transmitted virus (TTV)
  • West Nile virus (WNV)
  • Malarial parasites
  • Prion agents
  • Blastomycosis
  • Cryptococossis
  • Diptheria
  • Ebola
  • Leptosprirosis
  • Mycobacterium tuberculosis
  • Toxoplasmosis




The biggest concern after a needle stick in the health care setting is typically related to hepatitis B, hepatitis C and HIV.  Fortunately, today, virtually everyone working in the US health care system has been vaccinated against HBV.  There is no vaccine for hepatitis C, but it can be cured with medication.  Unfortunately, the medication used to cure Hepatitis C is extremely expensive. HIV is not curable, but can be managed effectively with expensive pharmacotherapy.

Fortunately, for me the source patient was HCV negative and I have immunity to HBV (although the patient was also negative for HBV).  My immediate focus was determining my probability for seroconversion to HIV positive.      I finished the case about 60 min after the percutaneous puncture, and went to the ER.  I received one dose in the ER of two reverse transcriptase inhibitors (emtricitabine and tenofovir) and one integrase inhibitor (Raltegravir) as part of the standard PEP regimen.

Contacting HIV after a needle stick injury is rare fortunately. From 1981 through 2006, the CDC documented only 57 cases of HIV transmission in HCWs following occupational exposure and identified an additional "possible" 140 cases. There are no high quality human studies to provide us any guidance on understanding the probability of seroconversion after a needle stick. The commonly cited risk of 0.3% transmission was from a study done in the late 80's and 90's where HAART therapy was non existent, thus creating a higher risk study population vs. today. In 1997, Cardo and colleagues identified four factors associated with increased risk for seroconversion:

  • Deep injury (Odds Ratio=15)
  • Injury with a device visibly contaminated with source patient blood (Odds ratio=6.2)
  • Injury from a needle that was in blood vessel (Odds ratio=4.3).
  • Exposure to a source patient who died of AIDS two months following the occupational exposure (Odds ratio=5.6)
Many sources declare that risk from a hollow bore needle stick exposure is greater than that of an exposure from a suture style needle. In a retrospective case-control trial published in the NEJM, the authors state that "no significant difference in risk was found between exposure involving a hollow-bore needle and that involving a suture needle" after univariate analysis.  This same study found after univariate analysis that risk of exposure to a large bore needle carried increased risk (14 times increased odds of seroconversion).  However, the authors noted that this meant a gauge of 16 or less.  In studies of needle sharing during IV drug use, the per use risk of transmission of HIV was only 0.67%. 
While the amount of blood contaminating a needle after a needle stick injury is an important consideration, so is the viral load of a source patient.  The viral load is greater during early HIV infection, before the immune system has had a chance to mount a response.  Pilcher et al.  estimated that viral load reaches its peak at 17 days after seroconversion in blood [2]. Likewise, in late stage AIDS, viral load will increase as the viral replication overwhelms the host patient's immune defenses.  The viral load varies from patient to patient but has a large effect on the conversion rates, where it is as low as 0.01% with viral loads less than 1,700 copies / mL, but closer to 0.3% when the viral load is greater than 38,000 copies / mL. This may explain the rate of seroconversion that occurs with a blood transfusion from an HIV infected blood source of 95%.  While this is high, why is it not 100%? You are receiving 300 to 350 mL of blood after all.  I suspect that it relates to the viral load of the source blood. The next highest risk activity to result in HIV infection is the birth process at 13 to 45%.  In decreasing risk, you then have needle sharing for IV drug use, unprotected receptive anal intercourse (0.5%), needle stick injury (0.3%), and exposure of mucous membranes to contaminated blood (0.09%). Of course, the probablities listed are averages from studies. After a needle stick injury, the risk for serconversion in that one event could be wildly different from that quoted due to all of the unknowns.  However, the good news is that it is low.




During acute HIV infection, the viral doubling time is approximately 10 hours and approximately 19 newly infected cells will develop from each HIV infected cell. Therefore, within 48 hours of infection, there will be more than 1.3 x 10^6 HIV infected cells. HIV  is also readily incorporated into the DNA of resting lymphocytes, where it exists in a non duplicating state. This is important because this DNA is not susceptible to anti retroviral therapy. This relates to the recommendations of what actions to take after a needle stick injury from an HIV infected patient.  The CDC currently recommends that after a needle stick injury from a known HIV infected patient to start triple drug pharmacotherapy within two hours of the accident and not greater than 72 hours after the injury.  It is recommeneded to continue this therapy for 28 days.  This recommendation is based on a variety of studies. The only human study we have relates to post exposure treatment mentioned above with ZDV [1]. In this case-control study, there was an 79% reduction in seroconversion when the HCW took zidovudine.  Animal models are also illuminating. therese studies when therapy was begun immediately or within a few hours and continued for days to weeks it was effective in reducing rates of seroconversion. Pharmacotherapy was ineffective if begun after 72 hours.  In animals treated with chemoprophylaxis within 24 hours of inoculation infection was prevented.  However, if there was a delay of 48 hours, 1/2 of the animals became infected and half again became infected if the delay was 72 hours.  Others studies have found a similar result.  Likewise, therapy lasting only three days in animals resulted in 100% rate of seroconversion whereas, therapy lasting 10 days resulted in a seroconversion rate of 50%, whereas a 28 day course of chemoprophylaxis prevented infection in all animals tested. In Africa there have been several retrospective studies tracking HCWs exposed to HIV and using PEP. The PEP regimens were typically based on zidovudine, plus one or two additional medications. In these small studies there were zero cases of seroconversion despite a large number of those exposed failing to complete their PEP regimen. 

Currently the CDC is recommending triple drug regimen for PEP.  This is based on two concepts. 1) it is likely that the effectiveness of PEP is related to the host's immunological response and ability to clear the HIV virus from the body, indicating that PEP is more a treatment than a prophylactic, and 2) in more robust studies looking at vertical transmission in pregnancy there is a study showing that rates of transmission are 20%,10%, 3.8% and 1.2% if mothers received no therapy, ZDV mono therapy, two drug therapy, and triple therapy respectively. 
Understanding cases of post exposure prophylaxis (PEP) failure is also illuminating.  There have been 24 cases of reported failure that can be verified in the literature as of 2014. In these cases, 75% of the patients used single agent zidovudine as their PEP.  There has been only six cases of failure with multiple agent prophylaxis regimens. There are also cases of failure of PEP in HCW only to discover after further testing that the HCW was infected by another source outside of work after the completion of PEP or that PEP was not continued. (as Hard as that is to believe-I mean who gets exposed to HIV at work, starts PEP, and then contracts HIV in the community?)

The take home message on PEP is this:  If it is to be effective, the number of drugs you take is probably less important than making sure the full 28 day course is completed.  If a triple drug regimen is stopped early due to side effects/toxicity, then clearly mono therapy or dual therapy would be more effective if tolerated the full 28 days.  This fact is born out in studies showing that triple drug therapy is cause for a greater number of side effects and issues with toxicity. However, the issues related to toxicity have been greatly diminished with newer medications (see below).  However, the newer medications are also extremely expensive which can also be a barrier to full treatment.

The first line PEP regimen is Truvada + Isentress.  Truvada (Gilead) is a combination of emtricitabine and tenofovir. These medications are in the class if HIV drugs known as NRTIs or nucleoside reverse transriptase inhibitors.  They block HIV's ability to convert its RNA into DNA.
Insetress (Raltegravir) is an integrase inhibitor. After HIV has successfully used its own enzyme reverse transcriptase to make make a copy of its RNA into DNA, raltegravir inhibits this DNA's ability to integrate into the host's DNA.

There are now a large number of different anti-HIV medications available.  What exactly one should use for PEP may depend on a number of factors and may require consultation with an infectious disease specialist.   However, if the source patient has an undetectable viral load, PEP is not necessary.  An undetectable viral load means that a real time PCR is unable to detect any virus free in the blood.  The PCR test today can detect down to a threshold of 20 copies of RNA / mL of blood.  Another issue to consider is the cost. Truvada costs around $1500 for a 28 day regimen.  raltegravir is another $1200 or so.  No studies have been done to show that using a triple drug regimen is better than single drug PEP. The only evidence we have in humans for PEP comes from a case control study with zidovudine where HIV serconversion was decreased by 79% [1].  In my case, I looked at the factors that increase risk.  I was stuck fairly superficially (not deep) with a small gauge (25g) needle with no evidence of visible blood on the needle after a SQ injection of local anesthetic (i.e. needle was not placed directly into a blood vessel).  The patient's viral load was detectable (at the time of exposure we had no lab value as such), but she was taking four different medications for HIV. Since she was also pregnant,  I presumed that she was likely fairly compliant as she was likely motivated by her unborn child to reduce the chance of perinatal transmission of HIV. I also considered that I began therapy (truvada + isentress) early after exposure (2 hrs). Because I was financially responsible for the PEP regiment thereafter and discovering that GILEAD offered a free 28 day supply of truvada, I opted for this.  It is recommended with newer tests that you can test for HIV after four weeks. I tested negative at 4 weeks.  At 12 weeks, I will test again. However, if the first test is negative, there is a 95% chance the second test will also be negative.



Patients coming to surgery requiring anesthesia who are on antiviral therapy for HIV should be evaluated for toxicity from this therapy. Fortunately, newer agents used today are far less toxic than their older counter parts.  Nevertheless, potential toxicity exists for many of these agents and include problems such as:


  • dyslipidemia
  • hyperglycemia
  • insulin resistance
  • osteopenia/osteoporosis
  • anemia, neutropenia and thrombocytopenia
  • lactic acidosis
  • hepatic toxicity
  • peripheral neuropathy
Potential interactions with antiviral therapy and anesthetics must also be considered.  Propofol and NRTIs may both potentially promote mitochondrial toxicity and lactic acidosis. Enzyme induction or inhibition (CYP450 3A4) must also be considered.

  • rionavir/darunavir (protease inhibitors) can enhance the affect of opoiods and ketamine due to inhibition of liver enzyme CYP 3A4.
  • Saquinavir/ritonavir/darunavir (protease inhibitor) may inhibit midazolam metabolism and oral administration is particularly problematic; IV midazolam should be used with caution.
  • Ca2+ channel blockers (amlodipine, diltiazem) may be enhanced due to enzyme inhibition from darunavir (protease inhibitor)
  • Lidocaine and other amide local anesthetics (bupivacaine) may have increased blood levels due to enzyme inhibition since they are metabolized by CYP 3A4 if given to someone on darunavir or ritonavir.
  • Neuromuscular blocker effects may be prolonged due to inhibition of metabolism.
  • Aprepitant is metabolized by CYP 3A4 therefore, darunavir could increase aprepitant concentrations.
  • Dexamethasone is a CYP 3A4 inducer and therefore, at high doses over a long period of time can reduce the effectiveness of both darunavir and ritonavir in treatment of HIV. This should not be a problem with a single preoperative dose for PONV prophylaxis however.
  • Dexmedetomidine undergoes extensive hepatic metabolism and therefore, theoretically both darunavir and ritonavir could decrease dexmedetomidine blood concentrations requiring a larger dose.
  • Ergotamine is metabolized by CYP 3A4 and darunavir/ritonavir may lead to toxic levels if multiple doses are given.  This could lead to a life threatening event due to the narrow therapeutic window of ergotamine.
  • Labetaolol 

Conclusion
HCW are at high risk today to exposure to a number of infectious agents.  Needlevstick injuries continue to occur in HCW despite universal precautions.  HIV represents only one of these.  HIV infection continues to quietly cause a large number of infecctions worldwide and is an ongoing epidemic despite receiving little press.  Although HIV can now be managed with medications, life with HIV  significantly altered and complex when considering the complexity of the drug regimens, ability of the virus to become resistant, ongoing potential to infect others around you, expense of lifelong medications and infectious disease consultation, etc etc.  Therefore, needle stick injuries in the HCW produce a large degree of anxiety.  However, it is clear that the risk for seroconversion overall is low and is largely dependent degree of virus in the source patient's blood, amount of blood on the source needle, and degree of injury from the needle itself.  The risk of seroconversion can be further modified by determining the need for PEP within two hours of exposure, taking an appropriate regimen based on risk profile of exposure, and continuing the prescribed regimen for the full course (likely 28 days). Testing for HIV should be done at time point zero, 4 weeks, and again at 12 weeks to determine if serovconversion occurred.  In most cases of seroconversion, patients will experience full like symptoms associated with viral replication and the immune system's response to the virus.  HCW who experience a work related needle injury of low risk, and take the prescribed PEP as recommended have a very low risk of seroconversion, but unfortunately, the probability is not quantified due to lack of studies.






1. Bell, DM. et al. NEJM. 1997; 337:21:1485-1490.

2. Pilcher CD, Joaki G, Hoffman IF, et al.  AIDS 2007;21(13):1723-30.







March 16, 2020

Patient requesting labor epidural and a history of Idiopathic Intracranial Hypertension

This morning while watching the news showing the DOW plunging by another 2000 + points in the midst of a panicked public related to the spread of the novel corona virus, I was called up to L and D to place an epidural.  The patient was a G3P2 31 year old patient who was otherwise healthy with the exception of a reported prior history of Idiopathic Intracranial Hypertension.  She reported that she had been told that she could have an epidural by an anesthesiologist, but not a spinal.  Upon further questioning, I was able to determine that the patient had been treated by doxycycline for a routine URI or sinus infection.  Thereafter, she developed changes in her ability to see and sought medical care.  She was diagnosed with a reaction to the doxycycline and underwent lumbar puncture as part of the work up and therapy.  She states that after the lumbar puncture, she developed a headache which she had not suffered prior.  She was started on diamox and this was discontinued after a period of time.

At first glance, this seemed to be a case of primary idiopathic intracranial hypertension, when in fact, it was likely a case of secondary intracranial hypertension, meaning, caused by an external known cause rather than from a completely unknown cause.  Idiopathic intracranial hypertension is a diagnosis of exclusion. It typically affects females who are middle aged and obese. Upon LP, opening pressures of greater than 25 cm of H20 would be considered typical (normal opening pressure is 10 to 15 cm of H2O).  Patients with IIH can develop partial or complete blindness of one or both eyes if not treated.  In severe cases, when therapeutic LP or medicine like diamox or corticosteroids  are not working, surgical placement of an LP shunt is required.

For the OB anesthesiologist, any patient with potential intracranial pathology should be approached with caution.  Prior to any neuraxial procedure, it is important to fully understand the cause and natural history of any intracranial abnormality due to the potential catastrophic risk of brain tissue herniation.  An excellent review of the approach to the OB patient with intracranial pathology can be found here. In summary, patients who have obstruction to flow of CSF from the brain into the spinal canal are at high risk for any type of puncture of the dura mater. In the normal scenario when a puncture occurs of the dura mater in the lumbar portion of the spine, CSF will flow out and to compensate, CSF from the brain fills the space to equalize pressure throughout the continuous space. Any obstruction to this flow from from the cerebral ventricular system into the spinal canal will result in herniation.

However, patients with idiopathic intracranial hypertension (IIH) do not have a problem of obstruction of flow, and thus are not at risk for herniation after a dural puncture whether with a large bore or small bore needle.  As mentioned, LP is a therapeutic modality used to relieve headaches in these patients.  In patients with significant symptomatic IIH who wish neuraxial anesthesia for labor, there is a risk for potential exacerbation of symptoms (to include: pupillary changes or asymmetry, eye movement abnormalities, papilledema, hemiparesis, facial weakness, somnolence).   This is due to displacement of CSF from the lumbar spinal canal back up into the cerebral area. Furthermore, pregnancy and labor have been found to increase the baseline lumbar epidural pressure which it is thought is caused by engorged epidural veins. In studies of patients with elevated ICP, a 10 mL bolus of LA given over 20 to 30 s caused an average increase of 21 mmHg in ICP lasting 4.5 min vs an average increase of 6 mmHg for 2.3 min in a patient with normal pre injection ICP.  Therefore, this possibility should be discussed, and it may be a potential indication for a CSE, where a small IT dose can be given, and then a low volume infusion with PCEA can be offered to the patient to create a slow transition into epidural analgesia via lumbar epidural catheter. Indeed there are numerous case reports of successful neuraxial anesthesia for patients with IIH for both labor epidurals and cesarean sections. In this case report, the practictioner used the tuohy needle to drain 25 mLs of CSF prior to placement of an intrathecal catheter for labor analgesia. It was noted that the patient had excellent analgesia for labor and delivery, and did not suffer a PDPH, although the patient did complain of a headache.  Indications for an IT catheter might include patients where avoidance of GETA is important and likelihood of cesarian is also high.  The authors of the case report felt that their patient fell into this category.  They also noted that in a patient with difficult to control increased intracranial pressure, bolus doses through an epidural catheter may not be tolerated.

It is known that tetracycline, doxycycline and minocycline can all result in elevated intracranial hypertension.  Therefore, anytime a patient is treated with these antibiotics, any headache should prompt careful evaluation for this diagnosis. Currently it is unknown how these antibiotics can result in this disorder, although there is speculation that the antibiotics interfere with the production of ATP at the site of CSF absorption into the venous sinuses known as the arachnoid granulations.

My patient had been treated with Diamox or Acetazolamide, which is a carbonic anhydrase inhibitor. It is often noted that this action is predominantly effective at the renal tubule to reduce hydrogen ion secretion and increase the excretion of sodium, potassium, bicarbonate, and water.   Other uses include the treatment of glaucoma, seizures, and metabolic alkalosis due to its ability to dump bicarb and retain hydrogen ions. Diamox also inhibits carbonic anhydrase in the brain, and specifically in the choroid plexus, the site of CSF production, causing a decrease. Unfortunately, patients with IIH who are controlled with diamox will often be told to discontinue the medication while they are pregnant due to some case reports of congenital abnormalities and literature in animal models showing potential teratogenicity.  However, a recent study found no evidence for harmful effects of diamox in human pregnancy. Therefore, when a patient arrives for delivery, it is possible that she is still taking diamox to control her symptoms. If this is the case, it will be important to consider the effects of diamox on a potential anesthetic, primarily the risk of hypokalemia.

Patients who arrive for labor are always at risk for the potential to require anesthesia for cesarian section.  While neuraxial anesthesia is the preferred method overall, GETA may be required for a number of reasons.  In this case, there is a question as to whether succinylcholine should be used as it may cause a minor increase in ICP.  Furthermore, careful consideration of PaCO2 managment will be important as any increase in ICP will accompany hypercarbia. Definitive measures used for decreasing the ICP include, mild head elevation, maintain EtCO2 between 25 mmHg and 30 mmHg, I.V. mannitol, continuous infusion of propofol, avoid hypoxia, hypercarbia, hyperthermia and hypotension.

Anesthesia OB management for patients with IIH is generally straightforward, but careful history and a detailed understanding of the patients history and manifestation are important to avoid confusion with other intracerebral pathology that may also present during the peripartum period, such as PDPH and venous sinus thrombosis that can make diagnosis more challenging.  

February 23, 2020

Severe toxic Megacolon secondary to Ischemic Colitis

A  76 Year old male was admitted to the hospital after a syncopal episode during a BM at home.  The patient was found to be constipated and admitted for further testing. The patient deteriorated in a day and a half and required intubation due to ventalitaory failure. Pressors were required in low dose shortly thereafter, with accompanying renal failure.  The GI physician was called in on Sunday morning to attempt colonic decompression via a colonoscopy and I was called into the hospital to provide anesthesia.  I explained to the GI doctor, that giving additional sedation to the patient might cause additional decompensation.  Therefore, I ordered the ICU nurse to given 30 mg of Rocuronium, so the GI doc could proceed without any movement from the patient. This was done about 8:30am without problems. However, the patient continued to deteriorate requiring max dose of Norepinephrine (30mcg/min) and vasopressin at 0.02u/min.  Patient was taken emergently to the OR at about 4:30pm sunday afternoon for ex lap and total colectomy with ileostomy.

Upon transport to the OR, the patient was receiving the above mentioned infusions, plus insulin 4 u/hr, diltiazem for new onset AF, Bicarbonate drip, and precedex at 0.2 mcg/kg/hr.  These were all continued during surgery with the exception of the diltiazem.

 Upon arrival to the OR I placed a left radial arterial catheter for invasive pressure monitoring.  US was used and visualizing of the artery revealed a virtually pulseless distal artery despite NIBP blood pressures reading 100/50 mmHg.  After cannulation, there was almost no pulistile flow from the catheter causing me to question whether I had cannulated the artery or a vein. After connection to the transducer, an obviously arterial tracing was visualized on the monitor.  However, there was a very wide discrepancy between the NIBP  reading and the AL reading.  In general, the NIBP of the same arm was 45 mmHg higher for systolic pressures. All attempts to reduce this discrepancy failed.  The waveform was not dampened, there was excellent blood flow when withdrawing from the AL, the transducer was carefully zeroed twice, and placed at a similar level as the NIBP cuff.  The cuff was on the same arm as the AL.  Therefore, throughout the case, the AL was used mostly for trending, while I chose to accept the NIBP reading as more indicative of the actual pressure experienced by the patient.

Here are some serial ABGs
The patients labs were as follows: (day of surgery was 2/16).
ABGs (serial)
2/13--7.2
2/14--7.37
2/15--7.5
2/15--7.3 19:00 (lactate 7.2)
2/16--7.013
2/17--7.027
Na+: 138 mEq/L
K+: 4.2 mEq/L
Cl-: 99 mEq/L
CO2: 21
BUN: 54 mg/dL
Cr: 4.3 mg/dL


The patient was on  a bicarb infusion and I continued this to the OR.  I admit that I found this unusual and wondered what the evidence was to support treating severe lactic acidosis  from severe ischemic colitis with bicarbonate therapy.  In general multiple studies in critically ill patients with metabolic acidosis have not found any benefit to bicarbonate therapy for improving outcomes.  However, in one small study, patients with lactic acidosis AND AKI did have improved mortality when treated with bicarb [1].  In studies on patients in code situations, bicarb therapy has not improved outcome and is likely contraindicated.  Bicarb is most definitely indicated for patients with RTA I, or proximal RTA where bicarbonate is wasted, or not efficiently reabsorbed by the kidneys. However, RTA I leads to a chronic metabolic acidosis and is not relevant to our patients condition.  To me, it is not clear that our patient met the criteria of the patients in the study that found a benefit of bicarb therapy.  Prior to surgery the patient was anuric and had near complete renal failure, as opposed to AKI.  In the above mentioned study, it should be noted that the authors found that in patients who did not have AKI and were treated with sodium bicarb, there was an increase in mortality after correction for disease severity. The authors noted that this may be related to the fact that severe acidosis inhibits the enzyme phosphofructokinase which is responsible for the production of lactate.  By increasing pH, this enzyme is unleashed to continue to produce additional lactate worsening the acidemia unless the underlying cause of the production of lactate is corrected.  It is of note, that in the cited above study, patients treated with sodium bicarb did not see a reduction of blood lactate levels to the degree of those patients with a similar acidemia who did not receive sodium bicarb therapy. It should be noted that in non mechanically ventilated patients, sodium bicarb therapy for metabolic acidosis can be particularly detrimental since this therapy rapidly increases gaseous CO2 in the blood. As PaCO2 increases, a respiratory acidosis may ensue, and as CO2 rapidly enters cells, intracellular acidosis may become significant evens as blood HCO3- decrease.

It is noteworthy, that prior to surgery, my patient's lactate was 7.2 mg/dL, after surgery it had jumped to 12.2 mg/dL.  Lactate clearance has been shown to be  much better predictor of mortality than other  predictors [2]. In the ARISE trial, septic patients with high lactate levels had higher mortality than those who presented with hypotension only [6].  This massive increase also lends weight to the evidence described above that bicarb therapy may worsen lactate production, although, in this case the patient's on going significant disease burden most likely greatly contributed to the rocketing lactate levels seen. Indeed, 24 hours later, his lactate level had jumped to 18.9 mg/dL and the patient expired not long after this.

Another question that arose early in the case was related to the dose of vasopressin. Due to low blood pressure and the already high dose of norepinephrine, I attempted to increase the infusion rate of vasopressin to 0.05 u/min.  The pump had been preprogrammed to disallow this dose. Therefore, I was forced by the pump to limit my infusion to 0.04 u/min.  To me this seemed too low of a dose.  An excellent review of the pharmacology and endocrinology of vasopressin can be located here.  In an early study on vasopressin for septic shock, the dose used to show benefit was 0.07 u/min.  In hemorrhagic shock, it is recommended to use doses near 0.4 u/min and in post cardiac surgery vasodilatory shock a dose of 0.1 u/min is recommended and was found to be devoid of adverse effects. Therefore, evidence exists to allow for higher infusion rates of vasopressin when combined with norepinephrine in a patient in severe shock.

Pre-pro-AVP is synthesized in magnocellular neurosecretory neurons (also known as neurohypophyseal neurons) in the supraoptic and paraventricular nuclei (known as osmoreceptors) of the anterior hypothalamus. It migrates along the supraoptic-hypophyseal tract to the posterior pituitary gland, where it is stored in neurosecretory vesicles and is then secreted in response to decreased stretch on atrial, aortic and carotid body mechano receptors.  Vasopressin acts on receptors labeled V1, V2 and V3. V1 receptors are located on vascular endothelium, kidneys, platelets, and brain and V2 receptors are predominantly located in the kidney collecting duct where they cause an increase in aquaporin insertion in the walls of the collecting ducts to allow increased water reabsorption into the blood.   In refractory shock, the enhanced sensitivity to exogenous vasopressin may be attributable to its ability to block KATP channels, interfere with NO signaling, bind avidly to V1receptors, and potentiate the effects of adrenergic agents at the level of vascular smooth muscle in shock states.

Vasopressin has increased in popularity in ICUs in large part because of large and  well done studies such as VASST, where vasopressin (low dose 0.01 to 0.03 mcg/min) was found to be beneficial (decreased mortality by nearly 10%) in patients with low severity shock [4].  Furthermore, in a post hoc analysis of the data from this large study, Gordon found that patients who received vasopressin were less likely to advance to the loss or dialysis categories of RIFLE scoring system if they already had AKI (21% vs 40%) [5].   Unfortunately, in the VASST study, no difference in mortality could be found in those receiving vasopressin in addition to norepinephrine vs norepinephrine alone in patients with more severe sepsis, as was the case in our patient.

The surgery lasted approximately four hours. The patient received seven liters of crystalloid (LR), 1L of albumin and was essentially anuric.  Blood loss was minimal.  The patient was transported to the ICU ventilated, paralyzed with max pressors continued.  The patients lactate nearly doubled within 24 ours, the INR went to 4, d-dimer went very high, Hgb dropped despite no obvious blood loss, liver enzymes went to nearly 5,000, and K+ levels went to 6.9 mEq/L, while albumin dropped to less than 2 mg/dL. The patient was placed on CRRT and it became obvious that he was not going to survive.  The patient expired on POD #2 after parent multi organ failure with DIC.


1.  Kim HJ, Son YK, An WS. PLoS One. 2013;8:65283
2.  Lee SM, Kim SE, Kim E Bin, Jeong HJ, Son YK, An WS. PLoS One. 2015;10:145181
3. Dünser MW, Mayr AJ, Ulmer H, Knotzer H, Sumann G, Pajk W, Friesenecker B, Hasibeder WR
Circulation. 2003 May 13; 107(18):2313-9.
4. Russell JA, Walley KR, Singer J, Gordon AC, Hébert PC, Cooper DJ, Holmes CL, Mehta S, Granton JT, Storms MM, Cook DJ, Presneill JJ, Ayers D, VASST Investigators.
N Engl J Med. 2008 Feb 28; 358(9):877-87.
5.  Gordon AC, Russell JA, Walley KR, Singer J, Ayers D, Storms MM, et al. The effects of vasopressin on acute kidney injury in septic shock. Intensive Care Med. 2010;36:83–91.
6. Gotmaker R, Peake SL, Forbes A, Bellomo R, ARISE Investigators (2017) Mortality is greater in septic patients with hyperlactatemia than with refractory hypotension. Shock 48:294–300