Angiotensin Receptor Blocker (ARB) Reversal

From Angiotensin Axis Blocking Drugs In the Perioperative Period. Anesthesiology News, Feb 2016

What does an angiotensin receptor blocker (ARB) do?

Angiotensin II receptor blockers (ARBs) represent a newer class of effective and well tolerated antihypertensive agents 1. Several clinical studies have indicated the beneficial effects of ARBs in hypertensive patients such as reduction of left ventricular hypertrophy, decrease in ventricular arrhythmias, and improved diastolic function 1. Inhibitors of the renin-angiotensin system (RAS), either angiotensin converting enzyme (ACE) inhibitors or ARBs, mediate vasodilation and consequently decrease blood-pressure by different mechanisms 1. ARBs specifically inhibit angiotensin II from binding to its receptor, the Angiotensin-1 (AT 1) receptor on vascular smooth muscle cells. This blockade results in increased angiotensin II and normal bradykinin plasma levels. ARBs were developed to overcome several deficiencies of ACE inhibitors, which, by comparison, lead to decreased angiotensin II, but increased bradykinin levels. Hence, the key advantage of ARBs over ACE inhibitors is their lack of adverse effects related to bradykinin potentiation. ARBs have been shown to reduce morbidity and mortality associated with hypertension, and therefore, it is not surprising that an increasing number of patients scheduled for surgery are chronically treated with ARBs 2. However, RAS blockade increases the risk of severe hypotension during and after anesthetic induction. ACE-inhibitors are well known for inducing severe circulatory side effects during anesthesia, which led to the general recommendation to withhold the drug on the day of surgery 3.

Refractory hypotension during general anesthesia despite preoperative discontinuation of an angiotensin receptor blocker. F1000Research 2013, 2:12.

Comparison of Angiotensin‐Converting Enzyme Inhibitor and Angiotensin Receptor Blocker Management Strategies Before Cardiac Surgery: A Pilot Randomized Controlled Registry Trial. Journal of the American Heart Association. 2018;7:e009917.

Consequences of continuing renin angiotensin aldosterone system antagonists in the preoperative period: a systematic review and meta-analysis. BMC Anesthesiol. 2018 Feb 26;18(1):26.

From Angiotensin Axis Blocking Drugs In the Perioperative Period. Anesthesiology News, Feb 2016

How do I reverse an ARB in an emergency?

Chronic AT 1 blockade also reduces the vasoconstrictor response to α 1 receptors activated by norepinephrine, which explains why ARB-induced hypotension can be so resistant to phenylephrine, ephedrine and norepinephrine 2, 8 Clinical studies have shown significant vasoconstrictor effects of vasopressin and increased cardiac filling during echocardiographic measurements 2.

Vasopressin or its synthetic analogues can restore the sympathetic response and may be useful pressors in cases of refractory hypotension during anaphylaxis 9 and septic shock 10 as well as in patients on RAS inhibitors, although norepinephrine has been reported to have a more favorable effect on splanchnic perfusion and oxygen delivery 11.

Refractory hypotension during general anesthesia despite preoperative discontinuation of an angiotensin receptor blocker. F1000Research 2013, 2:12.

Angiotensin Axis Blocking Drugs In the Perioperative Period. Anesthesiology News, Feb 2016.

  • When conventional therapies such as: decreasing the anesthetic agent, volume expansion, phenylephrine, ephedrine, norepinephrine, and epinephrine are not effective, exogenous vasopressin may improve hypotension. To date, at least 5 clinical trials have demonstrated that patients on chronic ACEI/ARB undergoing general anesthesia, respond to exogenous vasopressin derivatives with an increase in blood pressure and fewer hypotensive episodes.6,7 Typically, a 0.5-1 unit bolus of AVP is administered to achieve a rise in mean arterial pressure.4 The subsequent recommended infusion dose is 0.03U/min for AVP and 1-2 mcg/kg/h for terlipressin. Caution should be used as V1 agonists have been associated with the following deleterious effects: reduction in cardiac output and systemic oxygen delivery, decreased platelet count, increased serum aminotransferases and bilirubin, hyponatremia, increased pulmonary vascular resistance, decrease in renal blood flow, increase in renal oxygen consumption, and splanchnic vasoconstriction.
  • Studies involving cardiac surgical patients suggest that MB treatment for patients with VS may reduce morbidity and mortality.5 It has also been suggested that the early use (preoperative use in patients at risk for VS) of MB in patients undergoing coronary artery bypass grafting may reduce the incidence of VS.5,9A bolus dose of 1-2mg/kg over 10-20 minutes followed by an infusion of 0.25mg/kg/hr for 48-72 hours is typically utilized in clinical practice and trials (with a maximum dose of 7 mg/kg).10 Side effects include cardiac arrhythmias (transient), coronary vasoconstriction, increased pulmonary vascular resistance, decreased cardiac output, and decreased renal and mesenteric blood flow.1 Both pulse and cerebral oximeter readings may not be reliable during MB administration due to wavelength interference.11,12 The use of MB is absolutely contraindicated in patients with severe renal impairment because it is primarily eliminated by the kidney.13 It may also cause methemoglobinemia and hemolysis.13 At high doses, neurotoxicity may occur secondary to the generation of oxygen free radicals. Neurologic dysfunction may be more severe in patients receiving serotoninergic agents such as: tramadol, ethanol, antidepressants, dopamine agonists and linezolid. Recommended doses for VS ranging from 1-3 mg/kg do not typically cause neurologic dysfunction.14 However, recent reports suggest that MB in doses even ≤ 1mg/kg in patients taking serotonin reuptake inhibitors (SSRIs) may lead to serotonin toxicity due to its monoamine oxidase (MAO) inhibitor property.15

Vasoplegic Syndrome and Renin-Angiotensin System Antagonists. APSF Newsletter, Circulation 94,429 • Volume 27, No. 1 • Summer-Spring 2012.

Vasopressin for persistent hypotension due to amlodipine and olmesartan overdose: A case report. Ann Med Surg (Lond). 2021 May; 65: 102292.

Vasoplegic syndrome following cardiothoracic surgery—review of pathophysiology and update of treatment options. Crit Care. 2020; 24: 36.

Refractory hypotension during general anesthesia despite preoperative discontinuation of an angiotensin receptor blocker. F1000Research 2013, 2:12.

Terlipressin for refractory hypotension following angiotensin-II receptor antagonist overdose. Anaesthesia, 2006,61, pages 402–414.

Angiotensin II for the Treatment of Vasodilatory Shock. N Engl J Med. 2017 Aug 3;377(5):419-430.

Vasopressin: physiology and clinical use in patients with vasodilatory shock: a review. Neth J Med. 2005 Jan;63(1):4-13.

Treatment of intraoperative refractory hypotension with terlipressin in patients chronically treated with an antagonist of the renin-angiotensin system. Anesth Analg. 1999 May;88(5):980-4.

Role of vasopressinergic V1 receptor agonists in the treatment of perioperative catecholamine-refractory arterial hypotension. Best Pract Res Clin Anaesthesiol. 2008 Jun;22(2):369-81.

Predicting response to methylene blue for refractory vasoplegia following cardiac surgery. Pharmacotherapy Conference: 2013 American College of Clinical Pharmacy Annual Meeting. October 2013.

Arterial Pulse Pressure Variation

Pulse pressure variation (PPV), which quantifies the changes in arterial pulse pressure during mechanical ventilation, is one of the dynamic variables that can predict fluid responsiveness. The underlying hypothesis is that large respiratory changes in left ventricular stroke volume, and thus pulse pressure, occur in cases of biventricular preload responsiveness.1

One of the most important concepts in resuscitation is volume responsiveness, or the ability of the cardiac output to increase in response to a fluid challenge.2

To measure the PPV in a given patient, that patient must have consistent and demonstrable cardiopulmonary interactions. This means that the patient must:

  1. Be in normal sinus rhythm
  2. Be intubated and be mechanically ventilated, making no spontaneous respiratory efforts
  3. Be ventilated with at least 8mL/kg of tidal volume
  4. Have no significant alternations to chest wall compliance, such as an open chest2


Left Atrial Occlusion Devices

Our hospital is starting to do more left atrial occlusion devices for people who have afib and aren’t able to tolerate blood thinners. Currently, two types are offered by our cardiologists: Watchman procedure (endocardial) vs Lariat procedure (epicardial).


It look and acts similar to a lariat or lasso.  An external guide wire with a magnet at its tip is introduced outside the heart towards the left atrial appendage (LAA). Another wire with a magnet at its tip is introduced from a groin vein and it traverses the interatrial septum to sit at the most distal point inside the LAA. The magnets “connect” and the lariat is introduced along the external guide wire and essentially lassos the LAA.

Lariat procedure

A large occlusion device is inserted via a groin vein and traverses the interatrial septum into the proximal (base or largest opening) left atrial appendage. The device gets deployed and successfully occludes the LAA.


PPT on Watchman from Boston Scientific

Is one better than the other?

Endocardial (Watchman) vs epicardial (Lariat) left atrial appendage exclusion devices: Understanding the differences in the location and type of leaks and their clinical implications.  Pillarisetti J, et al. Heart Rhythm. 2015.

CONCLUSION: The Lariat device is associated with a lower rate of leaks at 1 year as compared with the Watchman device, with no difference in rates of cerebrovascular accident. There was no correlation between the presence of residual leak and the occurrence of cerebrovascular accident.


For these cases, we typically have a good flowing peripheral IV and intubate these patients for general anesthesia. There’s a fair amount of TEE required for placement and verification of correct positioning of the device. Both procedures require transseptal access. Watch for hypotension as there is a risk for pericardial effusion.

TEE for Lariat

TEE for Lariat

TEE for Watchman

Watchman TEE

Echo Essentials for Endoluminal LAA Closure: April 2014 Cardiac Interventions Today

The WATCHMAN Left Atrial Appendage Closure Device for Atrial Fibrillation: J Vis Exp. 2012; (60): 3671

Anesthesia and Transesophageal Echocardiography for WATCHMAN Device Implantation: December 2016Volume 30, Issue 6, Pages 1685–1692.

From JACC: Cardiovascular Interventions
PDF Article

Percutaneous Left Atrial Appendage Closure
Procedural Techniques and Outcomes

3D Echo inside the Cath Lab – A must in LAA Closure. London, 2016.

ECHONOMY:Tools for Echocardiographic Calculations

YouTube: LEFT ATRIAL APPENDAGE CLOSURE PROCEDURE : Role of Transesophageal Echocardiography

YouTube: TCTAP 2015 SHD Live Case Session: LAA Closure

YouTube: How to image the inter-atrial septum using 3D-TEE “RATLe-90 maneuver”

YouTube: TOE in LA Appendage Assessment by Jason Sharp

** 2017**

Baseline TEE:
·       Full Scripps TEE protocol
·       Measure the LAA at the following views:
o   0°, 45°, 90°, 135°
·       Report the LAA maximal orifice, as well as the LAA dimensions at each angle using the following Xcelera drop-downs under “Left Atrium”:
·       Comment on presence or absence of atrial thrombus or “smoke”
·       Optional: Comment on LAA shape (ie: cauliflower, chicken wing, windsock, cactus)


Intra-Procedural TEE:
·       Comment on presence or absence of atrial thrombus

·       Report the LAA maximal orifice using the following Xcelera drop-down under “Left Atrium”:

·       Enter LAA device size and implantation date under the “History” section in Xcelera
·       Comment on the presence or absence of a residual leak using the following Xcelera drop-down under “Left Atrium”:
·       If a residual leak is present, comment on the size (mm) of the leak using the following Xcelera drop-down under “Left Atrium”:
·       Iatrogenic ASD with direction of shunting
·       Comment on any post-procedure pericardial effusion (compare to baseline)


Post-Procedure Discharge TTE (pt. in hospital):
·       LIMITED 2D TTE to rule out pericardial effusion (unless order specifies otherwise)
·       Spectral Doppler for respirophasic flow changes if an effusion is present


45-Day, 6 Month, 1 year and 2 year F/U TEEs:
·       Comment on presence or absence of atrial thrombus
·       Comment on the presence or absence of a residual leak using the following Xcelera drop-down under “Left Atrium”:
·       If a residual leak is present, comment on the size (mm) of the leak using the following Xcelera drop-down under “Left Atrium”:
·       Carry over LAA device size and implantation date under the “History” section in Xcelera

·       Comment on Iatrogenic ASD with direction of shunting, if still present

TAVR Team: conscious sedation vs. general anesthesia

Today, we had a guest speaker Christian Spies from Queen’s Hospital in Hawaii who spoke on his experience with his TAVR team and conscious sedation vs. general anesthesia for these patients.  More specifically, we are speaking of the transfemoral route.


  • Patient selection is key (consider for COPD; bad for OSA)
  • Short surgical time for monitored anesthesia care (MAC)
  • Decrease invasive monitoring (no PA catheter,+/-CVP)
  • No difference in hospital LOS or 1 year mortality rate
  • Move from TEE to TTE if MAC
  • Be prepared to convert MAC to GA (can be difficult in already tenuous patient in a crowded space under the drapes)
  • MAC agents: dexmetetomidine, propofol, ofirimev
  • Decrease pressor use
  • Develop an algorithm for MAC vs. GA and patient selection


For my own lit search:

***Update May 1, 2018***

We at Scripps Memorial Hospital in La Jolla do most of our transfemoral TAVRs via conscious sedation assuming appropriate patient selection.  These patients still tend to be the inoperable patients not cleared for open heart AVR (aortic valve replacement).  My techniques and choices for setup have changed over time as I’ve had a chance to fine-tune my plan based on prior experiences with TAVR.  Patients typically come to the hybrid room with a 20g PIV placed by the pre-op RN.

My Setup:

  • 4 channel Alaris pump:
    • dexmedetomidine @ 0.7 mcg/kg/hr until incision –> 0.4 mcg/kg/hr until valve deployment –> off
    • norepinephrine @ 2 mcg/min (titrating on/off, up/down as vitals suggest)
    • Isolyte (IV carrier fluid) @ 200ml/hr until valve deployment –> 50ml/hr
  • Cordis neck line
    • Initially, I would have the interventional cardiologist setup a femoral venous line since they’re getting access to the groin.  However, the cardiologist would use that femoral line for emergent ECMO cannulation and I would lose my venous access and have to depend on a measly 20g PIV.  Nowadays, I try for a short 14g or 16g PIV.  If I can’t get one, the patient gets an awake right IJ cordis for large venous access.
  • Hot line fluid warmer with blood-Y tubing: this is for hookup to a large PIV or cordis line
  • Right radial arterial line
    • I started only placing right radial arterial lines because there was a case of a dissection and I immediately lost my left radial arterial line and couldn’t do pressure monitoring.  I insist on only using the RIGHT radial for my arterial monitoring.  Do not let the cardiologist only give you arterial monitoring based on their femoral arterial access.  It will only give you intermittent monitoring and there are critical points leading up to the deployment where you need CONTINUOUS arterial monitoring.  Therefore, I’ve found the right RADIAL arterial line best for continuous monitoring.
  • Facemask for continuous oxygen at 10L/mim with ETCO2 monitoring
  • For trans-subclavian/axillary approach vs. transfemoral approach TAVR, I’ll put in a supraclavicular block right after Cordis/large-bore PIV venous access for patient comfort while still utilizing conscious sedation/MAC.

My Technique:

  • When the patient gets to the room, transfer patient to OR table.  Start IV fluids @ 200ml/hr.  Cases that go well are about 2 hours from start to end.
  • Facemask O2 at 10L/min.
  • Start sedation: precedex/dexmedetomidine @ 0.7 mcg/kg/hr.  Some patients may receive 1-2mg midazolam x 1 and 25-50mcg fentanyl for radial art line placement.
  • Place right radial art line with lidocaine for skin numbing.  Place PIV with lidocaine.  If unable to get access for PIV, prep neck –> sterile gown/glove/drapes for U/S guided Cordis placement with lidocaine.
  • OR staff preps patient.  Antibiotics prior to incision.
  • At incision –> precedex to 0.4 mcg/kg/hr.  25-50mcg fentanyl PRN discomfort. 10-20mg propofol push for discomfort if needed while large sheath placed for valve deployment.
  • Crossing valve –> BP changes.  Manage with volume or levophed.
  • Valvuloplasty
  • Don’t treat over-drive pacing too aggressively when the valve is deployed.  Typically, once the new valve is in, a little volume will help normalize the BP.
  • Once valve is deployed, turn precedex off.  No other sedation or BP meds needed.  Change IVF rate to 50ml/hr.
  • Patient heads to PACU awake, interactive, and comfortable.

What techniques do you like to do?  Any suggestions on a different approach?

Mr. Chill

CPR training
Image via Wikipedia

Feb 17, 2011

Today was an ordinary day.  Come in for a minimally invasive aortic valve and call it a day.  However, that case was cancelled secondary to UTI.  So, I opted to get involved in a different case…. an epicardial lead placement.  This was a gentleman I’ll refer to as Mr. Chill.  He was getting an epicardial lead placement b/c he was in heart failure and was going to undergo CRT.  He already had RA/RV leads and AICD.  He was a rather obese gentleman (280lb, 5’6″).  He had a history of amphetamine induced cardiomyopathy with an EF of 18%, inferior wall infarct and ant-sept wall infart, LV dilatation.  There was noted coronary sinus stenosis hence the need to abandon a coronary sinus lead and just go for the epicardial lead that would be placed via thoracotomy.  Aside from his heart history, he also had DM, HTN, AFib, sleep apnea (not using CPAP).  He’s on a whole host of meds… preop echo showed EF20%, severely decreased LV systolic function, hypokinesis of LV/RV, mild MR/TR, mod pulm HTN.

I met Mr. Chill in the pre-op holding area while a resident and CRNA were attempting to place PIV.  I took a look and you really can’t see anything.  So, while they were bringing the U/S, I was able to get a 22G PIV — not worthy of cardiac surgery…but worthy for induction.  A right radial a-line was placed with some difficulty (imagine poor EF…difficult to feel pulsatility anywhere).  The AICD rep was supposed to be available, but was running late so we were given the green light to go back to the OR.  The reason he earned the name Mr. Chill was b/c he was very relaxed and very interactive with us during PIV and a-line.  Every now and then he’d doze off, but then we’d say his name and he’d wake back up and interact with us.  I’m thinking that’s probably a combo of his OSA and his low flow state.

We brought him back to the OR, placed monitors on him.  The EKG appeared to be a wide complex regular sinus rhythm…someone who appeared to have a LBBB.  His a-line was reading 110-110SBP.  We were pre-oxygenating him for awhile.  Induction: lido 100mg, fentanyl 150mcg, etomidate 20mg, roc 70mg…after induction he stayed in the SBP90s.  Slowly, he started to drift down while taking over mask ventilation.  Luckily, he was an easy mask.  Now his SBP 80s, we intubate with a L DLT.  Confirmed with ETCO2.  SBP hanging in the 70s…multiple boluses of phenylephrine (total 600mcg), ephedrine (30mg), epi (100mcg) the SBP would go up to low 80s, but come back down to 70s.  We checked the DLT via FOI…it seemed a bit deep, therefore we pulled it back.  Still, we weren’t happy with it and his SBP was sagging, therefore, we took out the DLT and reintubated with an 8.0ETT.  Pt was oxygenating well as the SpO2 read 96-98%.  Then, his radial aline went to 60s. We cycled NIBP that showed 50s/20s.  Then the art line went flat.  We started CPR, 1mg EPI followed by atropine.  With CPR, the arterial trace looked good reading a pressure in the 80s.  PEA was suspect…we ran serial ABG, got femoral access.  We came out of it.  First ABG showed CO2 70s…ETCO2 was in the 40s.  We hyperventilated him and started him on an epi infusion.  The AICD rep interrogated his AICD…and we found out that the patient had 4 episodes of VT that was treated by overpacing from the AICD (not shocks).  This occurred in the pre-op area prior to going back to the OR and lasted for 35 seconds total.

We cancelled the case and took the patient to the SICU.

Things I took away from this case:

1) Always have the AICD rep interrogate prior to going to OR.  Period.  It doesn’t matter if everyone in the OR wants you to go… it’s worth waiting.  Obviously, Mr. Chill didn’t show any signs of VT to us b/c we were with him in the pre-op area.  There were no shocks delivered from the AICD.  Had I known he had 4 consecutive VT episodes that were worthy of AICD treatment via pacing, I’d have cancelled the case prior to going back to the OR.  Done!

2)  With an EF hanging around 10%, this guy is probably living off his sympathetic tone.  Do NOT give fentanyl, even if you think he may get tachycardic from the intubation.  Give it as it’s needed…even though it’s “cardiac stable”.  No one is stable with an EF10%.  The last thing I want to do is decrease any tone that may be supporting him. (Sure, maybe it’s a placebo for me… so be it!)

3) This guy’s PEA was most likely caused by hypercarbia.  He had a history of OSA and would intermittently fall asleep in the pre-op holding area… he may have been hypoventilating.  We didn’t see it on the ETCO2 trace while masking him b/c he probably has a large A-a gradient (ETCO2 registered on our monitors was 45).  His lungs are getting well ventilated…but his circulation time is so slow that he’s underperfused.  Dead space… and a lot of it.

4) For a guy like this, make sure surgeon and perfusionist are present in the room on induction.  They were present here…just an FYI.

5) R2 pads are always good to have in place, just in case.  Yes, this guy has an AICD… but at some point the treatment/shock mode will be turned off for the surgery.

6) Go with your gut instinct.  If your gut is telling you that he needs some beta activity to get the heart jumpy enough to tolerate induction… then do it.

7) Be a calm, cool cucumber during the resuscitation.  Our team did a fabulous job of communicating and getting things done… all b/c of clear, concise communication.  It really does make a difference.

8) Debrief.  This helps get everything on the table and brainstorm what could have been done differently or better.  We’re all colleagues; no one has room  to pass judgment.  Ever. (If they do, take’em out back and kick ’em in the shins!)

Call for help

April 11, 2010 (CA-3)

My 1st true difficult airway…. something I hope to never see again, but who am I kidding? It’s my job to be an airway expert… therefore, that only means I will be challenging my skills and will someday encounter that dreaded unintubateable airway.

The patient was a friendly, easy-going gal who was an anesthesiologist’s nightmare. She was coming in for a 3 vessel CABG… she was a known difficult IV access (yes, she came from the floor with an infiltrated 22g IV). She stood proud at 5’3″, 255lb, short chin, small mouth opening, and thick neck. She had had her cath done a couple days prior to her surgery — and yes, the radial artery was used. In addition to her already challenging anatomy, the surgeon requested that her other radial artery be spared for grafting.

I go to meet her in the holding area. She was so nice…friendly… had a positive attitude. These are the patients I love to care for. After updating her H&P and checking her consent, I apprehensively started searching for venous access. 3 PIV sticks..with flash but no luck. 2 attempts with U/S…no luck. Luckily, my a-line went in without any trouble. The attending tried several times for a PIV as well with U/S.. no luck.

We wheeled her back to the OR. She had a rather unchallenging R IJ MAC introducer placement (thank goodness!). Now to go to sleep!

We had a glidescope and bougie handy… knowing this intubation could be difficult. (In retrospect, I would’ve had the fiberoptic cart and an LMA within reach). We pre-oxygenated in reverse T-burg for what seemed like forever. Go time: Prop, sux,… glidescope…. barely saw arytenoids…even with a glidescope!! Small mouth opening kept us from truly getting the styletted tube in her mouth. I took a look for what felt like maybe 5 seconds and could eerily hear the sat probe dwindle down… 100….98……95……92….87….84…. time to mask ventilate!! We 2-hand mask her… a very difficult mask! Oral airway in…still difficult. Reposition, jaw lift,…sats 64…52….39… “Call for help” exclaimed my attending! I called out for an LMA and a bougie and told the surgeons to be on standby for an emergency airway.

Fortunately, we were able to place an LMA #4 and slowly ventilate her back up to 100% sat. By now, there were 3 other anesthesiologists and an anesthesia tech who came to help.

We had an airway, but couldn’t proceed with the surgery with just an LMA…we needed to secure her airway. We switched over to a Fast trach LMA#5…one that would accomodate a 7.0 ETT. We used a fiberoptic scope to look down the LMA. It was difficult to discern the structures. She had a pretty small glottic opening…and after several attempts, we were able to guide the fiberoptic scope down into the trachea and secure a breathing tube for ventilation.

Once the tube was secured… I took a step back and realized this could have been a disaster. However, we initiated all the right things in the difficult airway algorithm and saved this woman’s life. It was incredible.

After her surgery, we delivered her to the SICU, intubated. She was extubated the next morning under the supervision of an anesthesiologist. Everything went well. She recovered well from her CABG and was informed to have “difficult airway” written all over her medical record.

Key points:
-Call for help early
-Always have backup airway devices ready
-Even as a resident, don’t depend on your attendings to bail you out of trouble….b/c someday, that “attending” will be you.
-Reflect at the end of a challenging case