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

November 4, 2024

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

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


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

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

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

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

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

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

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




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

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

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

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

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

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



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