Only the A-E-I-O-U’s to start RRT and now we know “Y”! The Start-AKI Trial

In residency and med school we are always taught the indications for emergent CRRT as the mnemonic: AEIOU

metabolic acidosis with a pH < 7.1 Electrolytes hyperkalemia > 6.5 mEq/L refractory to treatment or rapidly rising levels in potassium
with dialyzable drug, including salicylates, lithium, isopropanol, methanol, and ethylene glycol (SLIME)
volume overload that does not respond to diuresis
especially with increased oxygen requirements
causing: uremic bleeding, encephalopathy, pericarditis, and neuropathy

However, in the ICU there has always been a question of how early should we start RRT in the setting of oliguria and BUN not causing symptoms. Initial thoughts were that earlier is better. Today’s infographic focuses on the latest RCT to determine the timing of CRRT. The Bottom Line here is that for the START-AKI TRIAL: Unless there is the emergent a-e-i-o-u’s to start CRRT doing it early does not appear to translate to a mortality benefit. There may be a signal of dialysis dependence at 90 days in this trial. Now we know “Y” we should wait until we have an indication other than the AEIOU’s.

Atrial fibrillation in the ICU: Tough AF to Treat, Sick AF to care for…

Peer Reviewed by Dr. Sagar Dave, DO

Every once in a while, it’s a good thing to get down to the nitty gritty of things. I think this is most helpful in common situations. Atrial fibrillation is one of those things to have quickly accessible in your internal brain. In this episode I want to go through some useful studies regarding atrial fibrillation (AF) in the ICU. As usual this is not a how to guide but my synthesis of select articles regarding atrial fibrillation in the ICU. As such this blog is not intended to substitute for medical knowledge by an experienced provider so this is not an authoritative review. It is intended to be an informational supplement that was briefly peer reviewed.  I divided this up into 3 sections. The first is the real down and dirty nitty-gritty painful detail. This is followed by a brief organized summary section ending with an even more abridged algorithm in an attempt to distill it all into a cohesive thought. So, read ahead with caution!  


  • AF Atrial fibrillation
  • CI: Confidence Interval
  • NOAF: New Onset AF
  • AA: Anti-arrhythmic
  • HR: Hazard ratio
  • RR: Risk ratio
  • DCV: Direct Cardioversion
  • EF: Ejection Fraction
  • OR: Odds Ratio
  • NE: Norepinephrine



Causes of AF 

AF risk factors in the critically ill have not been consistently linked to traditional risk factors associated with AF in the ED or community setting (ie, structural and valvular heart disease). It is thought that acute events during critical illness accelerate cardiac remodeling and fibrosis to rapidly produce a susceptible atria (the so-called “atrial substrate”). This allows for the development of sustained AF in as a result of the assault on the body in the ICU by a variety of arrhythmogenic triggers. Accelerated remodeling can occur due to infection and inflammation. Murine and primate models of pneumonia show that bacteria deposit within the myocardium and result in development of atrial fibrosis eve with the treatment with antibiotics. Furthermore, bacteria can alter ion channels gene expression through toxin release [Bosch et al., 2018]. In addition to the bacteria and response to critical illness, we in the intensive care unit further flagellate the heart. Dopamine and epinephrine in particular have chronotropic effects that can lead to increased atrial ectopic discharges triggering new AF. 

 Recall dopamine, in particular in the 2010 SOAP II Trial[a], almost doubled the rate of atrial fibrillation in septic patients (20% vs 11%) [De Backer et al., 2010]. 

Greater illness severity is also associated with the risk of new AF development. Lastly, atrial size on echocardiography is associated with new-onset AF in the ICU, suggesting that iatrogenic atrial pressure/ volume overload may also be important in the development of AF in the critically ill [Bosch et al., 2018].

Risk Factors Associated with AF

The above figure is from a study by Kanje and shows risk factors identified at the onset or immediately before the development of new-onset AF (n = 139)[Kanji et al., 2012].

In a study by Moss of 8356 ICU patients, 10% had new onset atrial fibrillation (NOAF). The strongest associations were acute respiratory failure, advanced age (> 60 yr), and sepsis[b] [Moss et al., 2017]. Weaker but still significant associations were postoperative state, severity of illness, hemorrhage, vasopressor requirement, valvular heart disease, gender, and chronic lung disease [Moss] [Ibid.]. Heart failure, kidney disease, and body mass index (BMI) were not significantly associated with NOAF [Ibid.].

Incidence of NOAF

Walkey[c] in 2011 published a retrospective cohort of a California Database of administrative claims -over 3 million hospitalized adults. Severe sepsis (n = 49,082) occurred in 1.56% of those hospitalizations. New-onset AF occurred in 5.9% of patients with severe sepsis vs 0.65% of patients without severe sepsis [Walkey et al., 2011].

In another study by Walkey in 2014 they identified138,722 sepsis survivors via a Medicare 5% sample. In that group 7% (9,540) had NOAF during sepsis, 24% (33,646) had prior AF, and 69% (95,536) had no AF during sepsis. AF occurred following sepsis hospitalization more commonly among patients with NOAF during sepsis (54.9%) than in patients with no AF during sepsis (15.5%) [Walkey et al., 2014].

In 2020, a study by Fernando found 10% of admissions had NOAF. 22.4% of those NOAF patients went on to have sustained AF lasting longer than 24h [Fernando et al., 2020]. 

Furthermore, we may be missing some AF. Moss performed a retrospective cohort of ICU admissions for NOAF using automated detection (≥ 90 s in 30 min). In 8356 ICU admissions there were 123 (1.5%) documented cases of NOAF. However, they found sub-clinical AF in 626 patients (7.5%) for an overall incidence of any NOAF of 9%. Furthermore, in the Moss study, only 123/749 (16%) were likely persistent [Moss et al., 2017]. 

I’m sure as time goes on and more elderly come into the ICU and technology advances to have minute by minute recordings of vital signs the incidence of AF will continue to rise. 

Hemodynamic instability and AF

This will be the hand waving portion of the day. It is VERY difficult to distinguish instability of AF vs instability of critical illness. In the ICU, incredibly sick patients are “stable” on 0.25 (or more!) mcg/kg/min of NE, 0.03 of epi, 0.03 of vaso and have gotten 4L of fluid.  We have to figure out if there is a driving force that is making the patient unable to come off support and is that driving force AF. In that sense, I submit that “stable”—critically stable or meta-stable—p atient in the ICU has a VERY different connotation (as opposed to denotation) than many might be used to. 

Interestingly, 37% of critically ill patients with NOAF developed immediate hemodynamic instability, 11% exhibited new signs of cardiac ischemia and heart failure [Bosch et al., 2018].

In a study by Kanji et al. those with unstable AF were more likely to be receiving vasopressors/inotropes at the time of AF onset (53% vs 29%), to have decompensated heart failure resulting in pulmonary edema within 24 hours before the onset of AF (18% vs 6%), or to have an initial ventricular response greater than 150 beats per minute within the first 6 hours of AF (35% vs 16%, P = .01) [Kanji] [Kanji et al., 2012]. 

For this reason, maybe looking for new heart failure, a faster rate and increasing need for vasopressor might be helpful (or might not…).

Rates of attempted cardioversion of AF during critical illness are low: in postoperative patients who developed AF, attempted cardioversion resulted in immediate conversion to sinus rhythm (SR) in 71% of patients, but after 1 h, only 43% patients remained in SR, and after 24 h, only 23% patients remained in SR [Bosch] [Bosch et al., 2018]

Side Bar: What is your MAP goal?

Typically, we (stringently) target a goal MAP of 60. However, can a lower MAP goal be tolerated in critically ill patients? While this is subject of much debate one author looked at the elderly patients and the use of a lower MAP goal (60-65mmHg)

Lamantagne performed a multicenter, open-label feasibility RCT of 188 patients and compared lower (60–65 mmHg) to higher (75–80 mmHg) MAP targets and found no difference in SECONDARY outcomes of mortality (28d) or Renal SOFA scores [Lamontagne et al., 2016].

This prompted a follow up RCT by the same investigators.  “The 65 Trial” randomized 2600 patients over age 65 to MAP >60 mmHg or >65mmHg. They found no difference in death (41% vs 44%) and no difference in CRRT (24% in both groups) or urine output. However this endpoint did not lower supraventricular arrhythmias (12 vs 13 episodes) [Lamontagne et al., 2020]. 

[See Blog post:

Side Bar: Is your [radial] arterial line accurate? 

I love putting in a good arterial line but often you will see numbers you cant interpret[d]. Thus, we end up comparing it to something else (like a BP cuff and BTW the MAPs should be within 10 of each other). From the two studies below maybe we should switch out that radial for a femoral arterial line in shocked patients with up trending vasopressor requirements? (A maximal intensity suggestion, I know)

One prospective observational study of 159 patients in septic shock compared simultaneous arterial measurements of radial and femoral lines. Mean difference between radial and femoral MAP was +4.9 mmHg; during high-dose NE (>0.1 mcg/kg/min) NE this increased to +6.2 mmHg (95% CI: -6.0 to +18.3 mmHg). MAP differences > 5 mmHg) occurred in up to 62.2% of patients with high-dose NE therapy [Kim et al., 2013].

A second prospective observation trial of 77 patients in septic shock also comparing simultaneous radial and femoral lines found a difference in 75.4% of cases up to 5 mmHg. Of those, 25% had gradients more than 5 mmHg, 20.4% had the femoral MAP greater than radial MAP and 4% had radial MAP > Femoral MAP. The interval (difference in no direction) ranged from 16 mmHg in the no-NE group, 18 mmHg in the low-NE group, and 19 mmHg in the high-norepinephrine group [Antal et al., 2019].

Is AF a harbinger of Acute MI or Pulmonary Edema

In the study by Kanji [Kanji et al., 2012] of 3081 patients over 1 year in the ICU they found 348 patients (10%) with AF. 4.5% of them had NOAF and 6% had preexisting AF. Acute myocardial infarction occurred for the first time in the 24 hours after AF in 7% (9/139) of the NOAF group and in the preexisting AF group in 4% (8/186). Acute pulmonary edema occurred for the first time in the 24 hours after AF in 4% (6/139) of the NOAF group and in the preexisting AF group in 2% (4/186).

Thus, while a small incidence it is something to consider and not just focus on the rhythm! I’m not sure we need to get troponin on every patient but I do think we take a good look at those ST segments on the ECG and even another reason to not settle for a monitor produced ECG.

Treatment Options

Obviously, this is not an exhaustive list. This is going to be a review of MY go to strategies. As always in medicine there are many options. This is just one person’s journey…

Should we treat atrial fibrillation at all (Do you even cardiovert, brah?!)

Before we actually talk about treatment, do we even need to treat atrial fibrillation in the sick patient? Obviously no one knows the answer to this. From above it does seem some of this is transient and never even diagnosed. However, in a retrospective descriptive cohort study from 2 urban ED’s Scheuermeyer looked at ED patients with atrial fibrillation and an “acute underlying illness” [Scheuermeyer et al., 2015]. They identified patients 416 patients who were divided into those treated for the underlying condition with AF and those treated only for the underlying condition. 135 had rate and/or rhythm control; 281 were not treated for AF  (35% of the treated and 30% of the not treated were diagnosed with sepsis). Of the 135 with AF control 19% had successful rate control and 13% had successful rhythm control. 40% of the treated for AF group had any adverse events; vs 7.1% of those not treated for their AF. Adverse events were divided into major and minor events:

  • 14% of the treated vs 1% of the untreated had major adverse events: hypotension requiring pressors and Intubation
  • 33% of the treated vs 7% of the untreated had minor events: hypotension requiring fluid bolus and bag-valve-mask oxygenation

Direct Cardioversion (DCV)

I love me some electricity! I’m comfortable doing it and we know in the ED setting it is safe and likely associated with shorter ED stays [Stiell et al., 2020]. Since ICU NOAF is not as well studied in the literature it is difficult to distinguish success of amiodarone vs DCV because they are so often used together. So this water is likely pretty muddy and DCV and amiodarone are entangled.

In a study by Kanji, DCV was attempted in 26 (19%) of 139 patients with new-onset AF, (70% had received amiodarone just prior or during DCV). Conversion to sinus for ANY duration occurred in 13/26 (50%) but was maintained for at least 24 hours in only  (27%) of 7/26. By comparison Conversion to sinus for ANY duration in the amiodarone group occurred in 103/116 (88%) but maintained for at least 24 Hours in only 24/116 (20%) [Kanji et al., 2012]. A low yield of DCV appears to be consistent in the only other study of DCV in critically ill. 

Mayr performed DCV in 37 patients. 13 patients (35%) converted to SR, of those 8 patients remained in SR (24%) at 1 hr, 6 patients (16%) at 24 and 5 patients (13.5%) at 48 hrs. Notably, this study used monophonic waveforms and anterolateral placement [Mayr et al., 2003]. It would seem if you are going to cardiovert, do it as early as possible near the onset as success seems to decrease. 

In the category of most unexpected, Blecher found that in cardioversion of AF in the ED, drug use PRIOR to electrical cardioversion reduced the success of electricity. This is OPPOSITE of what is commonly believed that slowing the ventricular response before attempting cardioversion increases the success rate, although there is little evidence to support this. Blecher (part of the Ian Stiell research powerhouse) looked at ED cardioversion for discharge home in 634 patients who underwent attempted cardioversion: 428 electrical, 354 chemical, and 148 required both. They had 378 successful and 50 unsuccessful electrical cardioversions. Medications used included: Beta-blockers (~33%), Sotalol (~10%), Amiodarone (~5%) and Digoxin (~2%). They found that 64% of those failing electrical cardioversion had the ventricular rate slowed before the attempt at electrical cardioversion versus 38.4% of those successfully converted. Thus, more failures at electrical cardioversion had rate control prior! They found rate control and prior attempted chemical cardioversion was associated with decreased likelihood of successful electrical conversion: OR 0.39 (95% CI 0.21–0.74) and 0.28 (95% CI 0.15–0.53)   [Blecher et al., 2012]. A clinically significant OR (Odds Ratio) is considered to be an OR 0.3 or less!

Electrode Positioning in DCV:

In (what I could find as) the only RCT of electrode positioning a study by Kirchhof[e] et al. of PERSISTENT AF, cardioversion was successful in a higher proportion of the anterior-posterior than the anterior-lateral group ([96%] vs [78%]). Cross-over from the anterior-lateral to the anterior-posterior electrode position was successful in 8/12 patients, whereas cross-over in the other direction was not successful (0/2) [Kirchhof et al., 2002].

Other observational trials have shown inconsistent results regarding electrode positions on the success.  In a meta-analysis of 10 trials with 1281 patients the anterior-posterior electrode position had no advantages in terms of success of electrical cardioversion [Zhang] [Zhang et al., 2014].

However, even in this trial they noted the only study without bias is the Kirchoff [Kirchhof et al., 2002] trial so I continue to use the AP position. Also, the AP position to me makes sense in CARDIOVERSION since you want to be across the atria, the anterior lateral position makes sense to me in DEFIBRILLATION since you are across the LV. Impedance of the chest wall is likely a large factor and is likely affected by BMI. You can ask me in person my strategy to overcome high chest wall impedance. It’s shocking!

Magnesium (Mg)

Don’t you wish sometimes we still lived in that blissful world of medical school and board exams where all cases of appendicitis are in the right lower quadrant, zebras roam freely, and all hypokalemia and hypomagnesima are the cause of AF?! Sadly not even the latter statement is true. 

Lancaster Incidence of AF does not correlate with Potassium (K) or Magnesium (Mg) serum levels. See Text

Lancaster in a study of 2041 post-operative AF (POAF) patients without pre-operative AF looked at just this idea. They found that in 752 patients with POAF patients had higher potassium and magnesium levels than matched patients POAF. Further more they found K, Mg supplementation did not reduce the rate of POAF [Lancaster et al., 2016].

It should be clear that cardiac surgery patients are a slightly different brand of AF but I wouldn’t be surprised to find this is true in the ICU as well. Nevertheless, I will continue to write K>4 and Mg>2 in my notes. 

Although it may be a surprise I do still believe that magnesium is capable of cardioversion in AF. A meta-analysis of magnesium for the prevention of postoperative atrial fibrillation in cardiothoracic patients found an odds ratio of 0.66 (95% CI: 0.51 – 0.87) [Henyan et al., 2005].

In a prospective single arm trial in critically ill patients a “step up” protocol by Sleeswijk of magnesium followed by amiodarone was shown to improve the rate of cardioversion [Sleeswijk et al., 2008]. Sadly this trial looked at only 26 patients. A Mg bolus (0.037 g/kg over 15 minutes) followed by infusion (0.025 g/kg/h) was given to all patients with persistent AF DESPITE correction of K, or Mg. While this is the equivalent of 4g of magnesium in a 100 kg patient, it should be nothing to be concerned about as this is a safe dose in patients with no renal disease and given frequently to OB patients[f]. The INFUSION was cut in half when Mg was >2.0 mmol/L and stopped when Mg >3.0 mmol/L. If no conversion in 1 hour then amiodarone (300 mg over 15 minutes, and infusion of 1200 mg/24 h) was started. The results:

  • 16/29 (55%) patients responded to magnesium alone
  • 11 of the remaining 13 responded to the addition of amiodarone 
  • 27/29 (93%) responded to the combination [Ibid.].

This study looked at the equivalent of 4 g OVER 15 min. Certainly nothing to freak out over. Previous studies have shown a benefit of Mg in patients with AF by increasing the success of pharmacological cardioversion and by decreasing the incidence of postoperative AF [Rajagopalan et al., 2016]. Sadly, the data for magnesium is not of the highest quality. 

Rajagopalan performed an RCT of chronic AF patients showed no difference in cardioversion with or without magnesium (86%). These patients were very different and had chronic AF and were in AF for 3-4 months prior. Even after 4 shocks up to 200J only 86% of these patients cardioverted to SR! As a side note in my favor 2/132 in the mag group converted to SR prior to cardioversion vs none in the placebo group. They found no drop in BP with the magnesium and no adverse events [Ibid.]. This information with other the studies makes me hopeful. 

In my opinion, I like using magnesium especially if it gives me 30 minutes to decided what I want to do and do a second look at the patient! 

Amiodarone for AF

Amiodarone is a very old drug and thus there are numerous different dosing recommendations. 

PDR: Adults Intravenous dosage recommendations [PDR].

  • Initial IV rapid infusion of 150 mg over the first 10 minutes. 
  • And Then 1 mg/min for the next 6 hours (total dose infused = 360 mg).
  • And Then, the infusion rate is lowered to 0.5 mg/min for the next 18 hours (total dose infused = 540 mg). 
  • And Then after the first 24 hours, a maintenance IV infusion of 0.5 mg/minute (720 mg/day) is recommended.
  • No and then! Intravenous amiodarone should not be administered for longer than 3 weeks.  
  • NOTE: The dose of amiodarone may be individualized

Conversion from intravenous to oral therapy [Goldschlager et al., 2000]:

  • If duration of IV infusion was <1 week, the initial oral dose is 800 to 1200 mg/day PO.
  • If 1 to 3 weeks, the initial oral dose is 400 to 800 mg/day PO. 
  • If longer than 3 weeks, the initial oral dose is 300-400 mg/day PO.
  • If there is concern about GI function, both oral and IV therapy should be maintained for a few days

Amiodarone Pharmacology and kinetics (Skip this unless you are feeling particularly nerdy) 

Amiodarone contains 37.3% iodine by weight. It is a Vaughan Williams (remember those) class III antiarrhythmic (AA) but produces activities with each of the 3 other classes as well. Other pharmacologic activities include: systemic/coronary vasodilation, phospholipase inhibition, and inhibition of thyroid hormone metabolism. N-desethyl- amiodarone (DEA), the major metabolite also has antiarrhythmic activity. The half-life of amiodarone is 20-47 days and that of DEA is even longer [Chow, 1996].

Amiodarone Side Effects

In adults, IV (not oral) amiodarone dosage adjustments are not required on the basis of patient age, or renal or hepatic functionThe likelihood of pulmonary fibrosis with short-term use of intravenous amiodarone appears small.There is a reported 3.4% incidence of hepatic enzyme elevations combined with at least possible hepatic dysfunction with IV amiodarone thus it is important to monitor hepatic function. Most studies exclude patients with thyroid dysfunction and it is recommended to check thyroid function once and then at 6 months if the patient is still on amiodarone [Ibid.].

Effects on Thyroid function 

Amiodarone induced hypo/hyper thyroid (AIH) and amiodarone induced thyrotoxicosis can occur (AIT). The prevalence of AIH is as high as 22%. Acutely, there is an increase in TSH (but usually <20 mU/L), an increase in both free and total T4, and a decrease in total and free T3. After 3 months, a new equilibrium is reached, and TSH normalizes. However, T4 will remain high, and T3 will remain low. It is best to avoid checking thyroid function tests during the first 3 months of treatment. Most patients who do not have underlying Hashimoto’s thyroiditis will have resolution after amiodarone is stopped. The prevalence of amiodarone-induced thyrotoxicosis (AIT) is much lower than AIH. AIT can occur quite suddenly and at any time during treatment. AIT is diagnosed based on a suppressed TSH with an elevated free T4. Given the beta- blocking effects of amiodarone, the classic findings of thyroxicosis are often absent. In equivocal cases, a T3 level can be helpful, with an elevated or high normal T3 indicating thyrotoxicosis [Goldschlager et al., 2007].

Pearl: Clinically, the most common findings may be weight loss or a change in warfarin dose.

Amiodarone Mechanism of Action

Interestingly, short term mechanism of action (single dose) mainly produces AV nodal refractoriness and prolongs intranodal conduction interval time, (Class II and IV).  The long-term activity is an increase in the action potential duration in cardiac tissues (Class III). Negative inotropy is the most consistent hemodynamic effect of IV amiodarone. In patients with normal ejection fraction (EF), negative inotropy is usually offset by a decrease in systemic vascular resistance to maintain cardiac output. Thus, patients with left ventricular dysfunction are at greater risk for decrease in cardiac output but this is likely only transient [Kosinski et al., 1984].

Amiodarone Dosing

I find that dosing of amiodarone to be incredibly provider dependent and that is likely due to the extreme variations in patient response to this drug. The pharmacokinetic reason for this is that lasma concentrations of the drug do not correlate well with observed clinical effect because of rapid distribution to tissues and high plasma protein binding [Desai et al., 1997].

A study by Kosinski showed this on the effects of a 300-mg bolus dose over 5 min, followed by a continuous infusion (1000 mg/24 hover 3-5 d) in 12 patients. Patients with the higher EF (>35%) had a small but significant increase in cardiac index following whereas patients with the lower EF (<35%) had a decrease in cardiac index (from 2.1 to 1.7 L/min), MAP and increase PA pressures which after 3-5 days were compensated for by peripheral vasodilation (decreased SVR). Two (out of 6) patients in the low EF group developed hypotension requiring pressors. They recommended a longer infusion for the 300 mg dose in low EF patients [Kosinski et al., 1984]. 

In 1983 a study by in Mexico, Faniel looked at 26 patients admitted to the ICU SPECIFICALLY FOR AF with RVR. They used 3 mg/kg (1983 weights as well) over 3 min vs 5-7.5 mg/kg over 30 min for a total of 1500 mg in 24 hours. 5 were unsuccessful and required cardioversion (4 of these 5 had HR slow to 50 bpm as reason for failure). Mean HR was 140 (55-200). The initial dose was followed immediately by a slow infusion of 600 to 1200 mg/24 h to reach a maximum of 1500 mg administered during the first 24 h. Mean conversion time was 170 min. They saw no hypotension. They noted “The longest reversion times were generally related to situations where small, repeated initial doses had been given. This mode of administration appears less effective than giving the same total amount in a single dose” (175 min vs 240 min, larger vs smaller boluses). They concluded: even if stable reversion is not achieved, then DC shock may be improved by the prior use of amiodarone (we just read above this may not be true). Overall they concluded that there was a good hemodynamic tolerance to their dose of 7 mg/kg over 30 min [Faniel and Schoenfeld, 1983].

In 2004, Hofmann looked at 78 AF patients in a CCU with advanced congestive heart failure or cardiogenic shock (SBP<90). 13 required pressers none were on mechanical circulatory support. Patients were given a single bolus of 450 mg of amiodarone via a PIV (over 1 min?). cardioversion was successful in 40 patients (51.3%) within 24 hours: sinus rhythm occurred in 25 patients (32%) within 30 minutes after amiodarone, and during the following 23.5 hours another 15 patients (19%) reverted to sinus rhythm. They noted “ In two patients, a decrease of systolic blood pressure from 115 to 80 mmHg and from 130 to 100 mmHg occurred within the first 5 minutes, but blood pressure returned to the initial values after 10 and 90 minutes respectively without specific intervention”[Hofmann et al., 2004].

Then in 2006, Hofmann looked at 50 consecutive AF with RVR patients and compared to amiodarone to digoxin. In this trial they excluded patients with SBP <100 and preserved Ejection Fraction (EF). They also looked at 450 mg of amiodarone via a peripheral IV (PIV)[g].  This time specifically stated as a bolus over 1 min. If the ventricular rate was above 100 bpm after 30 min, patients received another 300 mg IV. 28 patients required a second dose of amiodarone. Sinus rhythm conversion occurred quicker in the amiodarone group. SBP fell about 10 mmHg on average after amiodarone. 4 patients require fluid bolus. No prolongation of the QTc interval occurred [Hofmann et al., 2006].

AF: Amiodarone vs All comers

There are not a ton of great studies of drug choices and septic shock

A study by Balik looked 234 patients with septic shock requiring NE for propafenone vs amiodarone vs metoprolol. There were 177 in the amiodarone group, 42 in the propafenone group and 15 in the metoprolol group. The cardioversion rate was: 74% with amiodarone, 89% with propafenone, and 92% with metoprolol. The 28 day mortality was 50% in the Amiodarone group, 40% in the propafenone group, 21% in the metoprolol group. Multivariate analysis demonstrated higher 12-month mortality in amiodarone than in propafenone.  (HR 1.58 95% CI:1.04-2.38; p = 0.03) [Balik et al., 2017].

In this study by Delle Karth of amiodarone vs diltiazem (I can’t leave my ER roots, Kate!) in critically ill patients, they looked at 3 groups of patients in the ICU of 20 patients with Apache scores of 75. Approximately 75% of the groups required mechanical ventilation and catecholamine therapy, thus these were sick patients. The groups were diltiazem (25 mg bolus + 20mg over 24 hrs), amiodarone bolus(300mg), amiodarone bolus + infusion (300 mg+ 45 mg/hr for 24 hours). The primary outcome was a 30% reduction in HR and a secondary outcome was a HR <120. Diltiazem allowed for a 30% HR reduction in 70% of patients and a HR <120 in 100% of patients. Amiodarone bolus only allowed for a 30% HR reduction in 55% of patients and and a HR <120 in 50% of patients. Amiodarone +infusion allowed for a 30% HR reduction in 75% of patients and and a HR <120 in 95% of patients. Hypotension occurred in 6/20 in diltiazem group and 0/20 in either amiodarone group [Delle Karth et al., 2001]. Thus it appears my ED favorite may cause more hypotension in these very sick patients than amiodarone. 

Chapman studied IV procainamide and compared it to Amiodarone in 24 critically ill patients. IV amiodarone (3 mg/kg followed by 10 mg/kg/24 h, with repeat dose of 3 mg/kg at 1 h if no response) or IV procainamide (10 mg/kg at 1 mg/kg/min followed by an infusion of 2-4 mg/min for 24 h, and a repeat dose of 5 mg/kg at 1 h if no response). The patients were recruited from a mixed medical and surgical ICU. Most were on mechanical ventilation (20/24), had sepsis (18/24) and an avg APACHE score of 21. They found conversion to sinus rhythm by 12 h in 10/14 (71%) in the procainamide group and (7/10) (70%) in the amiodarone group. SBP was not significantly different from baseline for either drug [Chapman et al., 1993]. I happen to be a big fan of procainamide in the ED for conversion of AF for discharge home, however, I have not had experience using it in the ICU due to lack of availability. 

Esmolol atrial fibrillation, and Mortality?

In a study of esmolol in patients with septic shock in TACHYCARDIA (avg HR 109) (not due to AF), Brown looked at 7 (yes, 7 patients!…because the other 179 patients were excluded)… Inotropes (not vasopressors) were one of many reasons to stop treatment [Brown et al., 2018]. A review article by Arrigo states “We recommend to start with substances with a low risk profile and short half-life, such as beta blockers (see below), and to escalate to other substance classes such as amiodarone only in cases of contraindications or inefficacy…Our choice is esmolol”. They cite the reason as “[beta blockers] significantly reduces the risk of AF up to 40%, particularly in the [cardiac surgery] postoperative phase”. The recommend a dose of 10–20 mg to reach 1 mg/kg Bolus. If the MAP is >60 mmHg, start infusion at a rate of 0.05 mcg/kg/min and may increase q 30-minute intervals as needed for HR. They recommended use, especially, if a patient was on oral BB prior [Arrigo et al., 2014]. Unfortunately, this review gave no references to support the use of esmolol for NOAF in ICU patients.

Another review article by Bosch also recommends Esmolol as FIRST LINE in AF in critical illness however they also have no evidence for this. They state “Thus, use of BBs to treat arrhythmias during critical illness is a promising area of investigation.” [Bosch et al., 2018].

Although these review articles did not give any evidence for the use of esmolol in AF and the sepsis syndromes, I think much of the reason for these recommendations for esmolol in critically ill patients with AF likely stems from the next two studies we will discuss.  

 An open label Italian  RCT by Morelli looked at septic shock patients WITHOUT AF! 77 patients were randomized to esmolol in septic shock and 77 to usual care. This was a feasibility study so the primary outcome was heart rate. Remember that secondary outcomes are hypothesis generating! They did indeed manage to keep the HR down for their primary outcome. Additionally, they reported a 28d-mortality of 49.4% in the esmolol group vs 80.5% in the control group [Morelli et al., 2013].  Naturally, in 2013 this study made headlines. However, lets check those numbers! That was an 80% mortality in the control group!!! Thus 30% difference… Interestingly they also reported about a 500 ml reduction in fluid administration to the esmolol group. Normally, I hear “Esmolol? That’s a lot of fluid [administered]!” Very interesting indeed. 

While there is no RCT data on AF, septic shock and beta blockers, there is a very large prospective observation trial looking at different rate controlling drugs and their mortality. This one even has a subgroup of septic shock! 

Once again, Walkey performed this interesting observational study of AF and sepsis in 2016. The study was a retrospective cohort of billing data from about 20% of US hospitals. Importantly, we have no idea why the clinician chose the rate control method they did. They looked at 39,693 patients with AF during the first 14 days of hospitalization for sepsis treated with only one rate control drug. They found 36% treated with a calcium channel blocker, 28 % were treated with a beta blocker, 20% with Digoxin and 16% with amiodarone. In a propensity-matched analyses, BBs were associated with lower hospital mortality when compared with CCBs (relative risk [RR], 0.92; 95% CI, 0.86-0.97), digoxin (RR, 0.79; 95% CI, 0.75-0.85), and amiodarone (RR, 0.64; 95% CI, 0.61-0.69). This was similar among subgroups of:  new-onset AF,  preexisting AF, heart failure, vasopressor-dependent shock, or hypertension. Patients with vasopressor infusion/shock were compared. 

  • BBs vs CCBs: shock: RR, 0.86; 95% CI, 0.79-0.94; no shock: RR, 0.98; 95% CI, 0.91-1.06
  • BBs vs Digoxin: shock: RR, 0.79; 95% CI, 0.73-0.86; no shock: RR, 0.80; 95% CI, 0.73-0.88
  • BB vs Amiodarone in shock: RR, 0.64; 95% CI, 0.59-0.69; no shock: RR, 0.73; 95% CI, 0.65-0.81

The percent of patients on vasopressors per drug group was: BB 29%, CCB  26%, Dig 44%, amiodarone 64% [Walkey et al., 2016b]. It should be noted that regardless of how well a propensity matched score is done it can’t isolate bias like an RCT and association does not mean causation, so this needs to be interpreted with caution. On the other hand, if we use the numbers from Walkey and assume a 27% vs 42% mortality in beta blockers vs amiodarone; that gives a Number Needed to Treat of 6 patients to prevent 1 death with amiodarone. Finally, either there is a signal of a mortality benefit with beta blockers or amiodarone is a marker for sicker patients. As an emergency medicine trained person my first thought is for CCB or BB but in the shocked patient many are too hypotensive and I end up having to use amiodarone.  


Digoxin slows heart rate by increasing vagal tone; it is associated with low rates of hypotension but has a narrow therapeutic index. Observational studies show associations between digoxin use and increased mortality. Vagomimetic effects of digoxin may be less effective during critical illnesses characterized by high catecholamine states [Bosch et al., 2018]. Digoxin should not be considered as a first-line option for rate control due to its slow onset of action [Sibley and Muscedere, 2015]. So…no matter what ANYONE[h] says, Digoxin for AF is still a very 1950s Treatment… Hence we wont discuss pharmacology or dosing. 

Does Anything make NOAF better?

McIntyre performed a systematic review and meta-analysis of 23 RCTs with excellent methods and low risk of bias. They found that patients who had vasopressin + catecholamine vasopressor had a lower incidence of AF than did patients not on vasopressin:

  • 24% (136/559) had AF in the catecholamine + vasopressin group
  • 33% (182/554) had AFin the catecholamine only group

They found a risk ratio of 0.77 [95% CI, 0.67 to 0.88] (not something thought to be clinically significant but still statistically significant. Sadly, this study showed no benefit for mortality with vasopressin [215/529 (41%) vs 222/520 (43%)] [McIntyre et al., 2018]. A whopping 40% mortality in this group!

Treatment Duration

            While no one knows how long to keep anti-arrhythmic medications going, Kanji showed 18% of NOAF patients and 62% of patients with preexisting AF who survived to ICU discharge left the ICU in AF [Kanji et al., 2012]. Bosch reported, 70% of patients with new-onset AF and 14% of patients with preexisting AF converted for at least 24 hours within the first 48 hours from the onset of AF[Bosch] [Bosch et al., 2018].

Anticoagulation vs. Stroke Risk

It is unknown if administering anticoagulation in critically ill patients prior to DCCV decreases the risk of thromboembolic events or if there is an optimal timing of anticoagulation prior to DCCV [Ibid.].

In the large study by Walkey in 2014, 138,722 sepsis survivors were identified in a Medicare database. In those with new-onset AF during sepsis compared with those with no AF during sepsis, the NOAF group had a greater 5-year risk of hospitalization for ischemic stroke (5.3% vs 4.7%; HR, 1.22) [Walkey et al., 2014]. That is a 0.6% absolute increase in stroke.

In 2011, Walkey looked at AF, severe sepsis and stroke in the US. In over 49k patients with severe sepsis and NOAF, they found that 2.6% (75/2896) had in hospital stroke as compared to the 0.6%  (306/46,186) without severe AF for an adjusted OR of 2.70 (95% CI, 2.05-3.57; P < .001) [Walkey et al., 2011].

In the Kanji study in Canada, 348 patients and over 2322 cumulative patient days of AF in the ICU, no patients had a documented embolic cerebrovascular event, whereas 5 (9%) of 58 patients who received systemic anticoagulation had a bleeding event that required interruption of anticoagulation and at least 1 blood transfusion [Kanji et al., 2012].

In a 2016 cohort study of 38,582 hospitalized patients with atrial fibrillation and sepsis, Walkey found bleeding events were increased among patients who received anticoagulation (1163 of 13 505 [8.6%]) compared with patients who did not receive anticoagulation (979 of 13 505 [7.2%]). However, those patients did not have a significantly reduced risk of in hospital stroke (1.4%) compared to those receiving of anticoagulation during sepsis compared to those who did (1.3%)[Walkey et al., 2016a]. So bleeding ~1.4% vs stroke 0.1%.

Some recommend starting anticoagulation if the AF is persistent for more than 48 hours [Sibley and Muscedere, 2015]. Others recommend in patients without contraindications to anticoagulation whose AF persists following hospital discharge, anticoagulation should be initiated if moderate to high risk [Bosch et al., 2018]. Currently there is no quality evidence or guideline to guide decision making for atrial fibrillation in the critically ill. Based on this data and the bleeding risk in ICU patients it would seem not surprising that some patients are not started on AC. In fact, in a study in Canada systemic therapeutic anticoagulation was prescribed for 16% (22/139) of patients with new onset AF and 19% (36/186) of patients with preexisting AF while in the ICU [Kanji et al., 2012]. 

Mortality and morbidity associated New onset atrial fibrillation NOAF

In a retrospective analysis by Fernando in 2020 of 6 years of a registry from two Canadian ICUs  10% (1541 of 15014) patients were found have NOAF. These patients did not have a STATISTICALLY significant higher mortality (37.4% vs 29.9%) than patients without AF (OR1.002, p=0.31).  However, NOAF was associated with higher hospital mortality among ICU patients with suspected infection (aOR 1.21 [95% CI 1.08–1.37]), sepsis (aOR 1.24 [95% CI 1.10–1.39]), and septic shock (aOR 1.28 [95% CI 1.14–1.44]). They did have a statistically significant longer ICU stay by 1 day range: [4-14] vs [2-9].

In the 2014 study by Walkey, a multivariable-adjusted hazard ratio compared with patients with no AF during sepsis, those with new-onset AF during sepsis had greater 5-year risks of death (74.8% vs 72.1%; HR, 1.04; 95% CI,1.01-1.07) [Walkey et al., 2014].

In the 2011 study by Walkey comparing patients with severe sepsis with NOAF and severe sepsis without NOAF; they found a greater risks of in-hospital mortality (56% vs. 39%) [Walkey et al., 2011].

In a study IN CHINA, Liu looked at mortality of whether or not patients with AF converted to sinus. They found 503 eligible patients, including 263 patients with no AF and 240 patients with NOAF.  Of the 240 patients with AF, SR was restored in 165 patients, and SR could not be restored in 75 patients. The NOAF that stayed in AF group had the highest in-hospital mortality rate of 61.3% compared with the NOAF that converted to sinus group (26.1%) or the no NOAF (17.5%) group.  Interestingly the group that stayed in AF had higher baseline SOFA scores, APACHE scores, more norepinephrine use, more mechanical ventilation use and more dialysis. The group that has NOAF and stays in AF is likely a sicker group! Also note that a 61% mortality is really high (hopefully this was not confounded by an invisible virus!) [Liu et al., 2016]

Special Populations: Cardiac ICU and Lung Transplant

Until now I have mostly avoided discussing post-operative AF in cardiac surgery patients. I would go through the specifics of post cardiac surgery patients but the following review article does a way better job:

Lung Transplant Patients

Twenty-five per cent (25%) of lung transplantation patients developed atrial flutter or fibrillation, most frequently at day 5–7 post lung transplantation, and more commonly present in older recipients and those with underlying chronic obstructive pulmonary disease (COPD), but not in those with previously noted structural heart disease, or in those undergoing single rather than double lung transplants. Diltiazem can increase tacrolimus concentration and the lung transplant team should be notified to adjust the tacrolimus dose whenever diltiazem is started or stopped [Barnes et al., 2019].

Putting it all together….

So what to do, what to do…

So how do we put all this together? Keep in mind this is MY version of putting it all together (see the algorithm), there are lots of permutations and possibilities. I will also throw back a little Toxicology Bombastus[i] style that THERE IS NO BAD DRUG and only the dose makes the poison!  Well, let’s start at the beginning footnote always good place. Here, again to be sure, we are talking about the ICU patient who is very sick and develops new onset atrial fibrillation. Let’s use a sample case presentation:


Mr. Sic AF presents to your ICU and is admitted via the ED in septic shock. After 24 hours of treatment he is on 0.1 mcg/kg/min of norepinephrine, his map is 65 via a radial arterial line,  his HR is 115 and there is sinus rhythm on the monitor. He suddenly goes in to AF with a rate of 140 and his MAP is 61 now…what do you do wildcat (see corresponding algorithm)?!


  1. IF a patient becomes grossly unstable obviously resuscitate them.
  2. Get a real ECG if they are “stable” (see definition of stable)
    • Be a cardiologist here. Don’t substitute a monitor produced one, not one without a rhythm strip…An honest to god pink shiny papered ECG
  3. Is this rhythm causing additional instability more so than if they did not have AF? 
    • Is this tachycardia (AF or sinus) compensatory for the shock state as opposed to pathological and contributing to the current hemodynamic compromise
    • The atria supply about 25% of cardiac output and myocardial depression is common in sepsis especially in those who die of septic shock [Jardin et al., 1999]
    • Remember that unstable AF is more likely (but not impossible) to present with a HR of >150 (35% vs 16%)
  4. Do they NEED cardioversion?
    • Only cardiovert if you really think they are unstable
    • If you are going to cardiovert your best chance of success is in the first hour of AF. 
    • If you are going to cardiovert use the Anterior posterior placement
    • Remember only about 50% of cardioversion is initially successful and only about 1/3 successfully stay in sinus for 24 hours.
  5. Does this episode of AF need treatment?
    • Risk factors include age>60, chronic lung disease and sepsis [Fernando et al., 2020], [Moss et al., 2017].
    • Treat the underlying illness first if you think the high HR is due to critical illness then consider if the NOAF needs to be treated 
  6. Have the modifiable risk factors been sufficiently optimized?
    • Did you look at the ventricular function with bedside Echo?
    • Is there volume overload that can be optimized?
    • What are the electrolytes?
    • Are they acidotic?
    • Pressors: Avoid epinephrine and, especially, dopamine if possible
    • Can the pressor dose be titrated down without loss of blood pressure goals?
    • Can a lower MAP goal of 60 mmHg be tolerated [Lamontagne et al., 2020].
    • Is that [radial] a-line accurate? [Kim et al., 2013], [Antal et al., 2019].
  7. Give Magnesium[j]
    • I like to have a conversation with my local pharmacists, they are a wealth of knowledge and will let you know what your local hospital “policies” are as far as administration.
    • A small number of patients (but as high as 50%) might convert with this alone.
    • Give about 2g over 15-30 min (not 2 hours!) (consult your local hospital “ethereal” policy).  
    • If you want to give more magnesium then check repeat levels magnesium in a few hours (2-4 hours?)
  8. Choose and administer your anti-arrhythmic of choice
    • There are lots of choices here for the patient and treatment is usually based on personal preference. 
    • In a “stable” blood pressure diltiazem and esmolol are reasonable choices.
    • The aforementioned studies have looked at beta blockers while norepinephrine was infusing but not inotropes) 
    • observational data indicates that beta blockers might have a mortality benefit over amiodarone and digoxin (less so vs. calcium channel blockers) [Walkey et al., 2016b]. 
    • This needs yet to be confirmed in an RCT.
    • In the shocked patient who is on an inotrope or can not risk having more hypotension, amiodarone may be necessary.
    • Consider bolus of 150-450mg over 30 min then an infusion. See the algorithm for dose details.
    • The literature would suggest a 70% of patients but this will decrease by 24 hours and it will be mostly rate controlling. 
    • Amiodarone can initially WORSEN LV function and cardiac output but this will be offset in a few days by a decrease in SVR.
  9. Does the patient need to be anti-coagulated?
    • It would seem from above that less than 20% of patients are given AC to NOAF
    • These patients have a high bleeding risk (9% of those given AC have significant bleeding) so calculate a HAS-BLED score
    • It’s unclear that AC (vs prophylaxis dose) anticoagulation is helpful [Walkey et al., 2016a].
    • Think about it carefully then sleep on it some more before you do…you have time.
  10. These patients are sick AF!
    • The mortality of NOAF who Stay in AF is 40-60%!!!!
    • The mortality of NOAF who go to sinus is 26.1% (vs 18% in those without NOAF)
    • AF is likely a marker of illness as opposed to the cause of it so let the AF serve as a marker of someone who needs to stay on your radar!


Antal, O, E Ştefănescu, and N Hagău (2019), ‘Does norepinephrine infusion dose influence the femoral-to-radial mean arterial blood pressure gradient in patients with sepsis and septic shock’, Blood Press Monit, 24 (2), 74-77.

Arrigo, M, D Bettex, and A Rudiger (2014), ‘Management of atrial fibrillation in critically ill patients.’, Crit Care Res Pract, 2014 840615.

Balik, M, I Kolnikova, M Maly, P Waldauf, G Tavazzi, and J Kristof (2017), ‘Propafenone for supraventricular arrhythmias in septic shock-Comparison to amiodarone and metoprolol.’, J Crit Care, 41 16-23.

Barnes, H, G Gurry, D McGiffin, G Westall, K Levin, M Paraskeva, H Whitford, T Williams, and G Snell (2019), ‘Atrial Flutter and Fibrillation Following Lung Transplantation: Incidence, Associations and a Suggested Therapeutic Algorithm.’, Heart Lung Circ

Blecher, GE, IG Stiell, BH Rowe, E Lang, RJ Brison, JJ Perry, CM Clement, B Borgundvaag, T Langhan, K Magee, R Stenstrom, D Birnie, and GA Wells (2012), ‘Use of rate control medication before cardioversion of recent-onset atrial fibrillation or flutter in the emergency department is associated with reduced success rates.’, CJEM, 14 (3), 169-77.

Bosch, NA, J Cimini, and AJ Walkey (2018), ‘Atrial Fibrillation in the ICU.’, Chest, 154 (6), 1424-34.

Brown, SM, SJ Beesley, MJ Lanspa, CK Grissom, EL Wilson, SM Parikh, T Sarge, D Talmor, V Banner-Goodspeed, V Novack, BT Thompson, S Shahul, and to Control Adrenergic Storm in Septic Shock-ROLL-IN (ECASSS-R) study Esmolol (2018), ‘Esmolol infusion in patients with septic shock and tachycardia: a prospective, single-arm, feasibility study.’, Pilot Feasibility Stud, 4 132.

Chapman, MJ, JL Moran, MS O’Fathartaigh, AR Peisach, and DN Cunningham (1993), ‘Management of atrial tachyarrhythmias in the critically ill: a comparison of intravenous procainamide and amiodarone.’, Intensive Care Med, 19 (1), 48-52.

Chow, MS (1996), ‘Intravenous amiodarone: pharmacology, pharmacokinetics, and clinical use.’, Ann Pharmacother, 30 (6), 637-43.

De Backer, D, P Biston, J Devriendt, C Madl, D Chochrad, C Aldecoa, A Brasseur, P Defrance, P Gottignies, JL Vincent, and II Investigators SOAP (2010), ‘Comparison of dopamine and norepinephrine in the treatment of shock.’, N Engl J Med, 362 (9), 779-89.

Delle Karth, G, A Geppert, T Neunteufl, U Priglinger, M Haumer, M Gschwandtner, P Siostrzonek, and G Heinz (2001), ‘Amiodarone versus diltiazem for rate control in critically ill patients with atrial tachyarrhythmias.’, Crit Care Med, 29 (6), 1149-53.

Desai, AD, S Chun, and RJ Sung (1997), ‘The role of intravenous amiodarone in the management of cardiac arrhythmias.’, Ann Intern Med, 127 (4), 294-303.

Faniel, R and P Schoenfeld (1983), ‘Efficacy of i.v. amiodarone in converting rapid atrial fibrillation and flutter to sinus rhythm in intensive care patients.’, Eur Heart J, 4 (3), 180-85.

Fernando, SM, R Mathew, B Hibbert, B Rochwerg, L Munshi, AJ Walkey, MH Møller, T Simard, P Di Santo, FD Ramirez, P Tanuseputro, and K Kyeremanteng (2020), ‘New-onset atrial fibrillation and associated outcomes and resource use among critically ill adults-a multicenter retrospective cohort study.’, Crit Care, 24 (1), 15.

Goldschlager, N, AE Epstein, G Naccarelli, B Olshansky, and B Singh (2000), ‘Practical guidelines for clinicians who treat patients with amiodarone. Practice Guidelines Subcommittee, North American Society of Pacing and Electrophysiology.’, Arch Intern Med, 160 (12), 1741-48.

Goldschlager, N, AE Epstein, GV Naccarelli, B Olshansky, B Singh, HR Collard, E Murphy, and North American Society of Pacing and Electrophysiology (HRS Practice Guidelines Sub-committee (2007), ‘A practical guide for clinicians who treat patients with amiodarone: 2007.’, Heart Rhythm, 4 (9), 1250-59.

Henyan, NN, EL Gillespie, CM White, J Kluger, and CI Coleman (2005), ‘Impact of intravenous magnesium on post-cardiothoracic surgery atrial fibrillation and length of hospital stay: a meta-analysis.’, Ann Thorac Surg, 80 (6), 2402-6.

Hofmann, R, C Steinwender, J Kammler, A Kypta, G Wimmer, and F Leisch (2004), ‘Intravenous amiodarone bolus for treatment of atrial fibrillation in patients with advanced congestive heart failure or cardiogenic shock.’, Wien Klin Wochenschr, 116 (21-22), 744-49.

Hofmann, R, C Steinwender, J Kammler, A Kypta, and F Leisch (2006), ‘Effects of a high dose intravenous bolus amiodarone in patients with atrial fibrillation and a rapid ventricular rate.’, Int J Cardiol, 110 (1), 27-32.

Jardin, F, T Fourme, B Page, Y Loubières, A Vieillard-Baron, A Beauchet, and JP Bourdarias (1999), ‘Persistent preload defect in severe sepsis despite fluid loading: A longitudinal echocardiographic study in patients with septic shock.’, Chest, 116 (5), 1354-59.

Kanji, S, DR Williamson, BM Yaghchi, M Albert, L McIntyre, and Critical Care Trials Group Canadian (2012), ‘Epidemiology and management of atrial fibrillation in medical and noncardiac surgical adult intensive care unit patients.’, J Crit Care, 27 (3), 326.e1-8.

Kim, WY, JH Jun, JW Huh, SB Hong, CM Lim, and Y Koh (2013), ‘Radial to femoral arterial blood pressure differences in septic shock patients receiving high-dose norepinephrine therapy.’, Shock, 40 (6), 527-31.

Kirchhof, P, L Eckardt, P Loh, K Weber, RJ Fischer, KH Seidl, D Böcker, G Breithardt, W Haverkamp, and M Borggrefe (2002), ‘Anterior-posterior versus anterior-lateral electrode positions for external cardioversion of atrial fibrillation: a randomised trial.’, Lancet, 360 (9342), 1275-79.

Kosinski, EJ, JB Albin, E Young, SM Lewis, and OS LeLand (1984), ‘Hemodynamic effects of intravenous amiodarone.’, J Am Coll Cardiol, 4 (3), 565-70.

Lamontagne, F, MO Meade, PC Hébert, P Asfar, F Lauzier, AJE Seely, AG Day, S Mehta, J Muscedere, SM Bagshaw, ND Ferguson, DJ Cook, S Kanji, AF Turgeon, MS Herridge, S Subramanian, J Lacroix, NKJ Adhikari, DC Scales, A Fox-Robichaud, Y Skrobik, RP Whitlock, RS Green, KKY Koo, T Tanguay, S Magder, DK Heyland, and Critical Care Trials Group. Canadian (2016), ‘Higher versus lower blood pressure targets for vasopressor therapy in shock: a multicentre pilot randomized controlled trial.’, Intensive Care Med, 42 (4), 542-50.

Lamontagne, F, A Richards-Belle, K Thomas, DA Harrison, MZ Sadique, RD Grieve, J Camsooksai, R Darnell, AC Gordon, D Henry, N Hudson, AJ Mason, M Saull, C Whitman, JD Young, KM Rowan, PR Mouncey, and trial investigators 65 (2020), ‘Effect of Reduced Exposure to Vasopressors on 90-Day Mortality in Older Critically Ill Patients With Vasodilatory Hypotension: A Randomized Clinical Trial.’, JAMA

Lancaster, TS, MR Schill, JW Greenberg, MR Moon, RB Schuessler, RJ Damiano, and SJ Melby (2016), ‘Potassium and Magnesium Supplementation Do Not Protect Against Atrial Fibrillation After Cardiac Operation: A Time-Matched Analysis.’, Ann Thorac Surg, 102 (4), 1181-88.

Liu, WC, WY Lin, CS Lin, HB Huang, TC Lin, SM Cheng, SP Yang, JC Lin, and WS Lin (2016), ‘Prognostic impact of restored sinus rhythm in patients with sepsis and new-onset atrial fibrillation.’, Crit Care, 20 (1), 373.

Mayr, A, N Ritsch, H Knotzer, M Dünser, W Schobersberger, H Ulmer, N Mutz, and W Hasibeder (2003), ‘Effectiveness of direct-current cardioversion for treatment of supraventricular tachyarrhythmias, in particular atrial fibrillation, in surgical intensive care patients.’, Crit Care Med, 31 (2), 401-5.

McIntyre, WF, KJ Um, W Alhazzani, AP Lengyel, L Hajjar, AC Gordon, F Lamontagne, JS Healey, RP Whitlock, and EP Belley-Côté (2018), ‘Association of Vasopressin Plus Catecholamine Vasopressors vs Catecholamines Alone With Atrial Fibrillation in Patients With Distributive Shock: A Systematic Review and Meta-analysis.’, JAMA, 319 (18), 1889-900.

Morelli, A, C Ertmer, M Westphal, S Rehberg, T Kampmeier, S Ligges, A Orecchioni, A D’Egidio, F D’Ippoliti, C Raffone, M Venditti, F Guarracino, M Girardis, L Tritapepe, P Pietropaoli, A Mebazaa, and M Singer (2013), ‘Effect of heart rate control with esmolol on hemodynamic and clinical outcomes in patients with septic shock: a randomized clinical trial.’, JAMA, 310 (16), 1683-91.

Moss, TJ, JF Calland, KB Enfield, DC Gomez-Manjarres, C Ruminski, JP DiMarco, DE Lake, and JR Moorman (2017), ‘New-Onset Atrial Fibrillation in the Critically Ill.’, Crit Care Med, 45 (5), 790-97.

Rajagopalan, B, Z Shah, D Narasimha, A Bhatia, CH Kim, DF Switzer, GH Gudleski, and AB Curtis (2016), ‘Efficacy of Intravenous Magnesium in Facilitating Cardioversion of Atrial Fibrillation.’, Circ Arrhythm Electrophysiol, 9 

Scheuermeyer, FX, R Pourvali, BH Rowe, E Grafstein, C Heslop, J MacPhee, L McGrath, J Ward, B Heilbron, and J Christenson (2015), ‘Emergency Department Patients With Atrial Fibrillation or Flutter and an Acute Underlying Medical Illness May Not Benefit From Attempts to Control Rate or Rhythm.’, Ann Emerg Med, 65 (5), 511-522.e2.

Sibley, S and J Muscedere (2015), ‘New-onset atrial fibrillation in critically ill patients.’, Can Respir J, 22 (3), 179-82.

Sleeswijk, ME, JE Tulleken, T Van Noord, JH Meertens, JJ Ligtenberg, and JG Zijlstra (2008), ‘Efficacy of magnesium-amiodarone step-up scheme in critically ill patients with new-onset atrial fibrillation: a prospective observational study.’, J Intensive Care Med, 23 (1), 61-66.

Stiell, IG, MLA Sivilotti, M Taljaard, D Birnie, A Vadeboncoeur, CM Hohl, AD McRae, BH Rowe, RJ Brison, V Thiruganasambandamoorthy, L Macle, B Borgundvaag, J Morris, E Mercier, CM Clement, J Brinkhurst, C Sheehan, E Brown, MJ Nemnom, GA Wells, and JJ Perry (2020), ‘Electrical versus pharmacological cardioversion for emergency department patients with acute atrial fibrillation (RAFF2): a partial factorial randomised trial.’, Lancet, 395 (10221), 339-49.

Walkey, AJ, RS Wiener, JM Ghobrial, LH Curtis, and EJ Benjamin (2011), ‘Incident stroke and mortality associated with new-onset atrial fibrillation in patients hospitalized with severe sepsis.’, JAMA, 306 (20), 2248-54.

Walkey, AJ, BG Hammill, LH Curtis, and EJ Benjamin (2014), ‘Long-term outcomes following development of new-onset atrial fibrillation during sepsis.’, Chest, 146 (5), 1187-95.

Walkey, AJ, EK Quinn, MR Winter, DD McManus, and EJ Benjamin (2016a), ‘Practice Patterns and Outcomes Associated With Use of Anticoagulation Among Patients With Atrial Fibrillation During Sepsis.’, JAMA Cardiol, 1 (6), 682-90.

Walkey, AJ, SR Evans, MR Winter, and EJ Benjamin (2016b), ‘Practice Patterns and Outcomes of Treatments for Atrial Fibrillation During Sepsis: A Propensity-Matched Cohort Study.’, Chest, 149 (1), 74-83.

Zhang, B, X Li, D Shen, Y Zhen, A Tao, and G Zhang (2014), ‘Anterior-posterior versus anterior-lateral electrode position for external electrical cardioversion of atrial fibrillation: a meta-analysis of randomized controlled trials.’, Arch Cardiovasc Dis, 107 (5), 280-90.

[a] This Trial is a classic and a must read!

[b] As we all know there are at least 3 definitions of sepsis over time so the definition of this has changed thus shifting our ability to interpret these studies!

[c] This guy is everywhere in AF and Sepsis! Just check out the references!

[d] Look at those waveforms to make sure they have a dicrotic notch!

[e] No association with Kirchoffs rule of electrical current…and they say the universe has no sense of humor! As a refresher this law states that, for any node (junction) in an electrical circuit, the sum of currents flowing into that node is equal to the sum of currents flowing out of that node

[f] Magnesium: I like to speak with my local pharmacist and see what if any policy there is on mag administration because for some reason the OB floor can give a monitored pt 8g of mag but when I do it there is widespread panic. Still this is not the hill to die on though.

[g] Amiodarone can cause phlebitis and used to require a central line but this is no longer true. 

[h] You know who you are!

[i] Bombastus: Paracelsus born Theophrastus von Hohenheim (full name Philippus Aureolus Theophrastus Bombastus von Hohenheim) (1494 –1541). The father of toxicology! Sola dosis facit venenum “Only the dose makes the poison”

[j] Magnesium: Again know your local practices and staff comfort level. However, this is not a hill to die on.

What No COVID? Then at Least Lets Talk Steroids- in ARDS that is…

Reference: Villar. Dexamethasone treatment for the acute respiratory distress syndrome: a multicentre, randomised controlled trial. Lancet Respir Med 2020; 8: 267–76.

I know what you are thinking, “What gives? No COVID!” Well the two of you who read this are probably inundated with COVID info. So to give our brains a change I thought I would do a study that would DEFINITELY BE A HEADLINE if we weren’t COVID CRA. But just as DC gets overshadowed by Marvel so to this good (but slightly methodologically flawed) study may go unnoticed.

This study look at the utility of dexamethasone (dex) to treat MODERATE to SEVERE ARDS. I say this in bold because other trials didn’t have an entry criteria of a PaO2/FiO2 (“P/F” Ratio) of <200 (usually its worse like <150)…but this one did. Boy did they find a difference. The primary outcome was ventilator free days and they found that dex ALMOST halved this (7.5 vs 12.3)! Secondary outcomes (sloooowwww down those are hypothesis generating…quiet you, I want to be happy about something): All-cause mortality…halved!: (29 vs 50); ICU Mortality halved! (26 vs 43). Well not quite but pretty close. Now before we celebrate like its the end of social distancing* there are a TWO MAJOR FLAWS in the armor of this trial.


Flaw #1. Not only was it open label (the docs knew they were giving a steroid) but there WASN’T a placebo…what the what!!!! They state as follows:

“According to the ethical principles for medical research of the Declaration of Helsinki,19 the use of no placebo (no intervention) is acceptable when no proven intervention exists and when the patients who receive a placebo could be subjected to additional risks (eg, intravenous catheter-associated infections and interaction with other medications). The Spanish Agency of Drugs and Medical Devices and the referral Ethics Committee did not mandate a blinded design nor the administration of a placebo.”

“Although dexamethasone was not administered in a masked manner, the risk of assessment bias is very low because one of the outcomes of interest (mortality) is objective.”

Any who has ever been a patient or spent time as learner (and we are all learners) knows NOTHING is OBJECTIVE. The decision to take someone off the vent earlier COULD absolutely have been influenced.

Flaw #2: The trial was stopped short. The trial was calculated to have 317 parties with 157 in each arm but only ended up with 139 (+1) in each.
The trial was stopped at 88% enrollment due to low enrollment. Stopping a trial short can OVERESTIMATE the effect size.

A minor flaw in this study is that they also took less sick patients than other trials. As is the mantra with research “If it didn’t work, you didn’t give it early enough”…once again this was “right”.

Two good things they did correctly is look at new infections and hyperglycemia in both groups and found no difference.

That being said there looks like a signal here. Im sure when it comes down to it the GIANT changes seen here, they won’t pan out to be as big in real life but I bet there is something to giving dex to ARDS…at least I can hope. As an ER/ICU doc its another reason for me to give steroids… and you can’t spell stERoids without ER!

*I REALLY don’t like the term social distancing/isolation…we should call it “physical distancing/isolation”. We can stay in touch, without the touching!

Quick Hit Article: Difficult vascular access: You know the drill… but do you really know the drill?

Kawano et al. Intraosseous Vascular Access Is Associated With Lower Survival and Neurologic Recovery Among Patients With Out-of-Hospital Cardiac Arrest. Ann Emerg Med. 2018;71:588-596.

This study was a secondary analysis of a large EMS trial conducted in 7 sites in the US and Canada. This is a really interesting study that looks at the association between outcome and IO access. They looked at 12,500 pts with IV access and 660 pts with IO access. The primary outcome measure was favorable neurologic outcome at hospital discharge with a mRS of 0 to 3. In the IO group 24% had rosc, 4% survived to hospital discharge, and 1.5% had a favorable neurological outcome. In the IV group 38% had ROSC, 10% survived, 8% had a favorable neurological outcomes. In the UNADJUSTED propensity matched model IO vs IV access was associated decreased probability of ROSC (25% vs 34%,OR=0.66), survival to discharge (4.5% vs 8.6%, OR=0.5), and favorable neurologic outcome (1.8% vs 5.9%, OR=0.29). The two groups differed in interventions very noticeabley in that the IO group were an almost 15% LESS therapeutic hypothermia and 9% less interventional catheterization. This is JUST AN ASSOCIATION and maybe IO is just a marker of sicker patients, HOWEVER, I think this is enough to allow for an RCT looking directly at this topic.

Difficult IV access in cardiac arrest? Just drill it! Utilize intraosseous vascular access that is. The IO has become the go to for rapid IV access in cardiac arrest patients. We can deliver drugs quickly and not muck around looking for a vein either peripherally or centrally. But are there down stream consequences? Is it REALLY better? This study takes a look at outcomes of non-traumatic cardiac arrest patients who had an IO placed.

This study was a secondary analysis of a publicly available registry conducted in 7 sites in the US and Canada. The original trial looked at the timing of the first analysis for defibrillation and application of an impedance threshold device. The original data was prospectively collected. Exclusion criteria were the typical ones including trauma, prisoners, pregnant, dnr, and hypovolemia. To the study’s benefit the obtained a cohort whose access route was the INTENDED PRIMARY CHOICE and excluded failed attempts at either route of access. The importance of this is that it MIGHT equal out the bias of a sicker patient or delays in care where a failed access attempt delays the care. The primary outcome measure was favorable neurologic outcome at hospital discharge with a mRS of 0 to 3. This is an interesting outcome change point because normally mRS is 0 to 2 is the cutoff in stroke studies. Because out-of-hospital vascular access was not randomly assigned across this cohort, they applied propensity matching to decrease selection bias and unmeasured confounder.
They found after exclusions 13,155 patients with 660 pts (5%) and 12,495 (95%) pts. Note that patients with IO access had a higher proportion of nonshockable initial rhythms, fewer public location and shorter times from call to first provider. In the IO group 24% had rosc, 3.8% survived to hospital discharge, and 1.5% had a favorable neurological outcome. In the IV group 38.3% had ROSC, 10% survived, 7.6% had a favorable neurological outcomes. They found after multiple regression with multivariate analysis that IO access was ASSOCIATED with a DECREASED probability of ROSC [OR 0.6 (CI: 0.49 to 0.74)] and DECREASED favorable neurological outcome [OR 0.24 (CI: 0.13to 0.46)].
They found 1116 patients in the propensity match. In the UNADJUSTED model IO vs IV access was associated decreased probability of ROSC (25% vs 34%,OR=0.66), survival to discharge (4.5% vs 8.6%, OR=0.5), and favorable neurologic outcome (1.8% vs 5.9%, OR=0.29). Looking at the propensity matching these groups for the
Baseline characteristics are quite well matched and markers of their propensity matching were well correlated. They did differ in some ways in the interventions. The very noticeable differences in the IO group were an almost 15% LESS therapeutic hypothermia, 5% less fibrinolytics, and 9% less interventional catheterization.

Although the propensity scoring appears quite well and there were multiple calculations to correct for confounders there are still significant biases. I think foremost the discrepancy between the number of of IO vs IV’s performed is hard to overcome (660 vs 12500). Also there were some big differences in the patients receiving hypothermia and cardiac catheterizations. I still think the data is not definitive for those two interventions but certainly this may be a marker of quality of care and attention to care. Still the OR for survival with favorable neurological outcome is impressively in favor of IV access. It is interesting that some EMS systems used IO as their first line and it would be interesting to know why IO was first line. I also wonder WHY the IO patients got less interventions. Was the IV access the reason or were they initially deemed to be sicker? Also it would be nice to know how long the IO was in and what was the time frame to when it was swapped out for IV access. Lastly, I can’t get away from the thought that sicker patients are going to get IO’s and are going to do worse.

So what’s the bottom line? IO access is critical to establishing vascular access to care for patients (depending on what you think the validity of ACLS drugs are, oh HEY OPALS TRIAL). Maybe IO access is a marker for sicker patients or maybe worse IO access biases providers against the same level of care as those with an IV…We all know the drill… but does it make our patients better? I think this is enough to allow for an RCT looking directly at this topic.

LVAD Complications: A review

This is a nice little review by Dr. Long in Dallas entitled:

B. Long, J. Robertson, A. Koyfman, et al., Left ventricular assist devices and their complications: A review for emergency clinicians, American Journal of Emergency Medicine,


A ventricular assist device (VAD) can be placed into the right, left, or both ventricles thus the patient can have a right ventricular assist device, left ventricular assist device, or biventricular assist device. The goals of these devices include three different strategies: bridge to recovery, bridge to transplantation, or destination therapy (i.e., the patient is unlikely to recover and not a candidate for cardiac transplant). Contraindications to placement include metastatic cancer, irreversible renal/hepatic failure, and CVA with severe neurologic deficits. The LVAD has two basic designs which produce different patterns of perfusion, including the pulsatile and continuous-flow devices. More commonly these days are the non-pulsatile continuous flow devices.

Device Components

The continuous-flow LVAD has several basic parts including: the internal pump an external power source, and a control unit.The specific components of the LVAD include the inflow cannula, pumping chamber, outflow cannula, percutaneous driveline, controller, and power source. The inflow cannula, usually placed in the apex of the left ventricle (LV), provides the route for blood flow from the native LV cavity to the LVAD pumping chamber.

The pumping chamber, the component of the circuit which provides perfusion, is located in different positions depending upon the LVAD model type: the LV apex for the (HeartMate) HMIII and HVAD devices and the subdiaphragmatic space adjacent to the heart for the HMII device. The pumping chamber contains the impeller, a near-friction-less rotor with rotation speeds ranging from 2500 to 9800 rpm; these types of impeller designs can generate blood flow up to 10 L per minute. The outflow cannula provides the conduit back to the patient’s native cardiovascular system and connects the pumping chamber to the ascending aorta,

The percutaneous driveline provides a conduit for the electrical wiring, connecting the pump to the system controller. These wires not only connect the power source to the pump, but they also provide controlling and sensing functions for the LVAD. The driveline is tunneled

subcutaneously from the pump and exits the skin in the anterior abdominal area to connect to the controller. Thus, it is a frequent source of infection in the LVAD patient. The controller performs multiple functions and contains several important components. It controls LVAD functioning, including power source monitoring and regulation, overall system monitoring, data collection, and alarm system function. subcutaneously from the pump and exits the skin in the anterior abdominal area to connect to the controller. Thus, it is a frequent source of infection in the LVAD patient. 


A continuous flow LVAD will not typically produce a palpable pulse on its own, but patients may have enough native ventricular function to produce pulsatile flow and a pulse. A palpable pressure may also be due to pump thrombosis, and thus, it is important to determine if the patient has a palpable pulse at baseline. If a pulse is palpable, a standard sphygmomanometer may detect a blood pressure, which reflects a systolic blood pressure, rather than mean arterial pressure (MAP). If the pulse is not palpable, a pencil Doppler probe should be placed over the radial or brachial artery. The point at which Doppler signal returns corresponds to the MAP for continuous flow devices. If this is unobtainable, an arterial line may be required, which is the most accurate device for monitoring MAP. Invasive arterial monitoring will demonstrate minimal pulse pressure or flat arterial waveform. Caution is recommended in using pulse oximetry, as a low reading commonly reflects a lack of pulsatile flow. However, a normal value may be accurate. 

LVADs, especially those with continuous-flow, are sensitive to afterload and preload. Guidelines recommend maintaining a MAP of 70–90 mm Hg. Acute hypertensive adverse event is associated with MAP N110 mm Hg in patients with continuous flow pumps. The mechanical hum indicates device power and function. Signs of volume overload (extremity edema, ascites, elevated jugular venous pressure) can be due to subacute or chronic right ventricular failure. However, acute dyspnea, pulmonary edema, or hypotension are more commonly due to acute malfunction of the device, such as cannula obstruction or pump thrombosis. The device exit site, which is normally covered with a sterile dressing, and line should be examined with sterile gloves and mask for warmth, erythema, and discharge, which suggest infection. Finally, the patient should be asked if he/she brought the back-up battery and back-up controller. Sustained ventricular dysrhythmias may be due to underlying cardiomyopathy or decompressed left ventricle due to elevated pump speed or right ventricular failure. Patients with an LVAD will typically demonstrate normal sinus rhythm.


Chest radiograph provides important diagnostic information including position and the type of LVAD, as well as the presence or absence of an ICD or pacemaker. Deep space infection of the LVAD components requires assessment with computed tomography (CT). Sustained ventricular dysrhythmias may be due to underlying cardiomyopathy or decompressed left ventricle due to elevated pump speed or right ventricular failure. Patients with an LVAD will typically demonstrate normal sinus rhythm.

Echocardiogram can evaluate cardiac function and assess for complications such as regurgitation, right ventricular failure, and thrombus formation, though thrombi can be difficult to detect on ultrasound alone.  Key components of the assessment include valvular function, inflow/outflow abnormalities, ventricular size and function, and septal position.

Laboratory assessment includes hemoglobin/hematocrit, lactate dehydrogenase (LDH), haptoglobin, free hemoglobin, and coagulation panel. Hemoglobin and hematocrit with type and screen/cross are needed if concern of bleeding is present. Patients with LVADs are anticoagulated with a vitamin K antagonist, with a goal INR of 2–3 well as aspirin. Free hemoglobin and haptoglobin can assess for hemolysis. Elevated LDH >2.5 times the upper limit of normal suggests hemolysis, which is most commonly due to pump thrombosis in an LVAD patient.  Troponin is recommended in patients with new ECG findings, chest pain, or dyspnea. BNP is a sensitive indicator of volume overload in patients with an LVAD and may be elevated in those with new right heart failure or pump thrombosis or malfunction.

Patients should have a controller tag around their waist indicating the type of device, the institution that placed it, and a phone number. Alarms and functional parameters are shown on the external system controller. Pump speed controls flow. Pump power, flow, and speed should be noted, with assessment of alarms and battery. RPMs and pulsatility index must also be evaluated. 

LVAD specific complications:


A suction event is a common LVAD complication and is associated with low flow events, including dysrhythmia, hemorrhage, and other hypovolemic states such as diarrhea or vomiting.  Reduced LV preload results in collapse of the LV and decreased inflow into the LVAD. Low flow, speed, and power will be present on the controller. While bedside US can demonstrate decreased LV volume, this is often difficult in LVAD patients due to poor acoustic windows, and assessment of the LV diameter may assist in evaluating volume status. Treatment requires fluid resuscitation and managing the underlying etiology. With improved preload and intravascular volume, pump speed and flow will improve. 


Continuous-flow LVADs place patients at high risk of thrombosis, which may originate in the pump or the components such as the inflow or outflow cannula. Types of pump thrombi include acute catastrophic red thrombi entrapped within a fibrin mesh and white thrombi rich in platelets. Red thrombi form at the inlet and outlet areas due to blood stasis, while white thrombi typically form on the pump surface and are associated with turbulent flow. Thrombosis can result in pump dysfunction, hemolysis, emboli, stroke, and death, but patients with thrombosis present with a variety of symptoms due to these potential complications, ranging from no symptoms to cardiac arrest and death. On examination, evidence of hemolysis may be present with scleral icterus, dark urine, and fatigue. Serum LDH is typically >2.5 times normal. Urinalysis may demonstrate hematuria. Other important laboratory assessments include hemoglobin, free hemoglobin, haptoglobin, and coagulation panel. Thrombolysis may be required if patients are hemodynamically unstable. Emergent surgical pump exchange may be needed if the pump stops, the patient is unstable, or if alarms are present. 


Mechanical failure is the second most common cause of death in LVAD patients and may result from several different issues. Pump failure is the most important life-threatening complication requiring immediate care. The controller may demonstrate low flow, low voltage, and power loss. A low flow alarm should always be evaluated by first checking the power. Physicians should auscultate over the LVAD and evaluate for disconnected leads and cannula issues such as kinking or obstruction. A disconnected lead should be reconnected. However, if auscultation reveals no pump activity but all leads are in place, the clinician must assess power and power leads. If all leads are connected, the pump can be reset. If a power lead is not connected to the batteries or unit cable, the cable disconnect advisory will alarm and demonstrate a flashing symbol.  However, if the device has been off for over an hour and the patient is stable, consultation with the LVAD specialist is required, as the device should not be immediately restarted due to high risk of thromboembolic events. In the setting of hemodynamic instability, the device should be restarted immediately no matter the duration of stoppage, with continuous anticoagulation. If the clinician and/or LVAD specialist cannot restart the LVAD, pump exchange is needed, which requires discussion with the LVAD specialist and surgeon. For patients with inadequate perfusion and hemodynamic instability without an alarm activated, resuscitation with IV fluids and standard ACLS protocol is needed.

LVAD-associated complications 


Patients with LVAD are at elevated bleeding risk. Bleeding can occur from several sources: pump connections, grafts in the conduits, and most commonly, mucosal surfaces such as the gastrointestinal (GI) tract. GI bleeding affects 15–30% of patients with an LVAD. Bleeding in the immediate postoperative period is often due to hepatic congestion associated with severe heart failure and the effects of extracorporeal circulation of the bypass machine. Patients may also develop an acquired form of von Willebrand factor (vWF) disease due to the high shear stress associated with LVAD circulation resulting in cleavage and deficiency of vWF. Bleeding in elderly patients with acquired vWF is more severe. Resuscitation of patients with significant hemorrhage with LVAD includes product replacement and reversal agent administration. However, reversing anticoagulation should be weighed with the risk of thrombotic complications, and consultation with the LVAD. Lesions are typically treated with coagulation or clips. Due to the risk of sensitization and reducing the success of heart transplant, blood product transfusion should not be reflexive in patients who are hemodynamically hemodynamically stable. Leukoreduced and irradiated blood products are recommended if available. Octreotide has demonstrated efficacy in LVAD-related GI bleeding in several studies. Desmopressin can be provided, which is a synthetic analogue of vasopressin, or infusion of vWF concentrates. Discussion of platelet transfusion is needed with the LVAD specialist if the patient is thrombocytopenic and bleeding, as well as those with severe hemorrhage.


Ischemic and hemorrhagic stroke can result in poor outcomes and demonstrate a prevalence of 6.8% and 8.4%, respectively. There is an increased risk with every 5 mm Hg increase in systolic blood pressure. The ENDURANCE trial found a lower stroke rate with MAP 90 mm Hg, with patients receiving close blood pressure control demonstrating a 24.7% reduction in total neurologic events and 50% decrease in hemorrhagic stroke rate. Acute ischemic stroke more commonly affects the right cerebral hemisphere in patients with an LVAD. 


Patients with an LVAD are at high risk of sepsis, with rates of infection approaching over 42% in the first year post-implant, usually 2 weeks to 2 months. The driveline and VAD pump pocket are the most common infectious sites, with 80% of driveline infections occurring in the first 30 days of transplant. The system controller may demonstrate a high-flow alarm with distributive shock due to loss of vascular tone. LVAD-related infections include those that may occur in patients without an LVAD, but occur with greater frequency in LVAD patients such as mediastinitis, endocarditis, and bacteremia.  Non-LVAD infections include pneumonia, Clostridium difficile infection, and urinary tract infection (UTI). Within the first 3 months post implantation, the most common sources of infection typically include catheters, pneumonia, and C. difficile, while later sources of infection are more commonly related to the device.  Only half of patients will demonstrate fever, leukocytosis, or meet criteria for systemic inflammatory response syndrome. Discussion with the LVAD specialist and cardiothoracic surgery is recommended.  Deep infections typically require surgical debridement, while persistent bacteremia may require removal and implantation of a new device. 

RV Failure

RV failure is a major cause of morbidity and mortality, occurring in 15–40% of patients. Late onset right heart failure is increasingly being reported with RV dysfunction, ventricular dysrhythmias, pulmonary hypertension, tricuspid regurgitation, and device thrombosis or malfunction. This can result in reduced preload to the LV, decreasing LVAD flows and triggering a low-flow alarm. RV failure may result in elevated liver function tests, creatinine, and lactic acid. RV failure requires inotropes and/or vasopressors, pulmonary vasodilators, and LVAD specialist consultation. Patients may require careful fluid resuscitation, with 250 mL boluses. 

Ventricular Dysrhythmias

Patients may tolerate severe ventricular dysrhythmias with minimal symptoms due to the LVAD producing adequate cardiac output to meet end organ perfusion despite poor venous return. Patients often have an ICD prior to LVAD placement. Dysrhythmias may eventually result in compromised blood flow and can also contribute to RV dysfunction, suction events, thrombus formation, and poor perfusion. The controller will demonstrate low flow in patients with hypotension due to the dysrhythmia.

Aortic Regurgitation

Aortic regurgitation (AR) may develop de novo in up to 25% of patients after LVAD placement. AR more commonly occurs in patients with a closed aortic valve compared to patients in whom the valve frequently opens. AR results in decreased LVAD efficacy and may require modifications in pump speed, managed by the LVAD specialist. Patients may require aortic valve replacement.


Standard procedures for resuscitation are recommended as needed. Hypotension in LVAD patients is defined by MAP <60 mm Hg. Patients who are conscious should be assessed with history and examination, with close assessment of volume and perfusion status. ECG and bedside echocardiogram are vital components of the assessment, with analysis of LVAD components. Patients who are unresponsive and hypotensive require external chest compressions. Literature suggests no cases of dislodgement during cardiopulmonary resuscitation (CPR). If the patient has a MAP N<50 mm Hg or end tidal CO2 <20 mm Hg with a device possessing an audible hum, perfusion is likely adequate, and compressions are not necessary MAP <50 mm Hg without an audible hum in the unresponsive patient is associated with compromised perfusion and requires chest compressions at the same depth and frequency as in those without an LVAD. Defibrillation should be performed for unstable ventricular dysrhythmia. The pads should be placed distant from the pump, and if an ICD is present, the pads should not be placed directly over the ICD. In patients with adequate perfusion and respiration but who remain unconscious, evaluate for hypoglycemia, stroke, hypoxia, sedation, and coma.


Chest thoracostomy with chest tube placement in the setting of trauma with pneumothorax and/or hemothorax is recommended, but clinicians must avoid the driveline. Arterial line placement can be beneficial, and US guidance is recommended. Pericardiocentesis should be avoided due to risk of serious device complications, but it is recommended in the case of pericardial tamponade with hemodynamic compromise.





Recent Recommendations in Neonatal Resuscitation 2019 UPDATE

Sometimes we need a reminder and update on the basics… Your Welcome..

Recent Recommendations and Emerging Science in Neonatal Resuscitation. Pediatr Clin N Am 66 (2019) 309–320.

– The 2017 NRP guidelines recommend a 30- to 60-second delay in clamping in all term and preterm infants not requiring resuscitation.

– If the placental circulation is disrupted (e.g., placental abruption), the cord should be clamped immediately. Investigators found that delayed clamping reduced mortality before discharge.

– Another option is to clamp and cut a long segment of the cord immediately after birth and then milk the cord. The major advantage of either method of cord milking is that the newborn can be passed to the awaiting resuscitation team without delay while preserving the receipt of the placental transfusion.
– Delivery room temperatures should be at 23 C to 25 C (74 F–77 F).

– Suctioning of newborns should be performed only if the airway is obstructed or if PPV is needed.
– In nonvigorous infants born through meconium-stained amniotic fluid (MSAF), current recommendations include only intubation and endotracheal suctioning for those who need it for ventilation or airway obstruction.

– It is recommended that room air (21% O2 at sea level) be used at the initiation of resuscitation in infants born at 35 weeks gestation.

– Failing to reach SpO2 of 80% at 5 minutes was associated with adverse outcomes including intraventricular hemorrhage, and risk of death was significantly increased with time to reach SpO2 80%.
– Endotracheal intubation is indicated for ineffective or prolonged positive pressure ventilation (PPV) or for special circumstances such as an abnormal airway anatomy.

– Chest compressions are indicated when heart rate remains less than 60 beats/min after at least 30 seconds of PPV. When chest compressions begin, supplemental O2 may be increased until the heart rate recovers and weaned rapidly afterward.
– Epinephrine is indicated when the heart rate is <60 beats/min after 60 seconds of chest compressions coordinated with PPV using 100% O2

Cardiac Arrest in Pregnancy: An 2019 UPDATE

Sometimes we need a reminder and update on the basics… Your Welcome..

Cardiac arrest in pregnancy. SEMINARS IN PERINATOLOGY 42(2018)33–38.

– The maternal heart rate increases by 20–30% or 15–20 beats per minute

– Cardiac output increases by 30–50% or 1.8 L per minute with the uterus receiving approximately 17% of maternal cardiac output in the third trimester.

– The diaphragm elevates by up to 4 cm in the third trimester causing decreased chest compliance

– Functional residual capacity decreases by up to 25% in the supine position at term.

– Pregnant patients experience mild respiratory alkalosis.


– Aortocaval compression (ACC) needs to be addressed during cardiac arrest management.

– The American Heart Association recommends manual left uterine displacement (LUD) throughout resuscitative efforts and during perimortem cesarean section until delivery of the infant.

– In the past, ACC was addressed by placing the patient in a tilt; however, this is no longer recommended.

– Numerous studies have shown that maternal tilt decreases efficacy of chest compressions, which hinders resuscitative efforts.

– Successful manual LUD can be performed from the patient’s right and left side.

– From the right side, the uterus is pushed upward and leftward to relieve pressure from the maternal vessels.

– Care should be ensured that the uterus is not inadvertently pushed down.


– The most common cause of maternal mortality is venous thromboembolism followed by preeclampsia and eclampsia.

– In an analysis of cardiac arrest in pregnancy in the United States the most common causes of arrest were hemorrhage, heart failure, amniotic fluid embolism, and sepsis.


– Chest compressions are performed in the same manner as for non-pregnant patients with a rate of 100–120 compressions per minute and a depth of at least 2 in with minimal interruptions.

–  The most recent guidance state that hand placement for chest compressions should be in the center of the chest on the lower portion of the sternum in the same manner as for non-pregnant patients.

Bag-mask ventilation with 100% oxygen with a rate of at least 15 L/min should be initiated immediately with a compression–ventilation ratio of 30:2.

– Early defibrillation should be provided when appropriate, and modifications in shock energy are not indicated. Studies have shown that transthoracic impedance is unchanged in pregnant patients. Providers should not delay or withhold defibrillation due to concerns for fetal safety. During defibrillation, a minimal amount of energy is transferred to the fetus, and it is safe to defibrillate a patient at any stage of pregnancy.

– Since airway management is more challenging, intubation should be attempted by the most experienced provider available with the use of a smaller endotracheal tube with a 6.0–7.0mm inner diameter to increase the likelihood of successful intubation.

– Medical therapy for cardiac arrest in pregnancy is no different than for non-pregnant patients.

– Medications do not require dose alterations, and no medication should be withheld due to concerns for fetal teratogenicity.

– During active CPR, the AHA guidelines recommend against fetal assessment, and all fetal monitors should be removed from the patient. The goal of CPR is to restore circulation in the pregnant patient. Evaluating the fetal heart rate is not helpful at this time and can interfere with maternal resuscitative efforts.
– PMCD should be initiated after 4 min of failed resuscitative efforts with the goal of delivery within 5 min of initiation of resuscitative efforts.

– As a caveat, if the mother has clearly non-survivable injuries, it is not necessary to wait to begin the PMCD. Transfer to the operating room is not recommended.

– With regards to technique for cesarean section, both vertical and Pfannenstiel incisions are acceptable and are at the discretion of the obstetrician. If the underlying arrest is secondary to trauma, a vertical incision is preferred given that it provides better visualization of the abdomen.
– If restoration of spontaneous circulation (ROSC) has been achieved without undergoing a PMCD, the patient should immediately be placed in the full left lateral decubitus position.

– The 2015 AHA guidelines now state that pregnancy is not an absolute contraindication, and therapeutic hypothermia can be considered on an individual basis.

Fill the Tank or Rev’ the Engine… WHOA, PUMP the BRAKES: Early fixed dose norepi for septic shock?

We all know hypotension is bad. But should we fill with fluids or rev up the heart with pressors. This begs the question does early norepi help prevent hypotension and mortality? Today’s quick hit article:

Permpikul C, et al. Early Use of Norepinephrine in Septic Shock Resuscitation (CENSER) : A Randomized Trial. Am J Respir Crit Care Med. 2019 Feb 1. doi: 10.1164/rccm.201806-1034OC. PMID 30704260.


In this prospective double blinded intention to treat analysis RCT conducted in Thailand the authors found that early fixed dose norepinephrine (0.05 mcg/kg/min) allowed for faster time to the primary outcome of “shock control” by 6 hours after diagnosis of septic shock. Shock control was defined as achievement of a MAP >65 plus urine output (>0.5 ml/kg/hr) and a lactate that cleared by 10%. They found no clinical or statistical increase in limb or organ ischemia even when norepinephrine was administered by peripheral access during the patient’s entire hospitalization. Lastly, a secondary (hypothesis generating) outcome of 28 day mortality showed a difference of 5% in favor of the fixed dose norepinephrine group which would be nice if that were real and reproducible.  


Syncope Admissions


This was a very interesting phase II, double-blind, placebo RCT with intention to treat analysis. That looked to answer the question of “shock control” in septic shock. Shock control (A COMPOSITE OUTCOME) was defined as achievement of a MAP >65 mmHg plus urine output (>0.5 ml/kg/hr) and a lactate that cleared by 10%. The interesting part comes in from their inclusion/exclusion criteria. Keep in mind that the population studied is one of the biggest predictors of generalizability in a trial. They excluded patient if they met the criteria of septic shock for MORE THAN 1 hour before randomization! I’m not really sure why they would do that. They screened 456 patients and excluded 136, 31 of which were because of shock for >1 hour.  Another weakness I found was that they did not report how they calculated the MAP and what percent had a-lines and what percent was calculated by non-invasively. This can be VERY important (See my post on MAP later). The final study randomized 155 patients to each group. The two groups looked otherwise pretty similar in their baseline characteristics. The intervention group was started on 0.5 mcg/kg/min fixed dose of epi and everyone was blinded to this intervention with a placebo in the control group. Time to getting norepi was pretty quick 93 minutes. Theoretically, you could say the norepi group could be differentiated by providers if they saw the BP go up. However, 20% of the normal saline placebo had an increase in the blood pressure.  Both groups were allowed to have open label norepi The primary outcome here was time to shock control by measured MAP, urine output, and lactate. So, that is not the most fair primary outcome since obviously time to shock control will be faster in the norepi group. 76% of the norepi group vs 48% of the placebo group met the primary outcome. An interesting feature of the study was in the COMPOSITE primary outcome less than 10% of both groups reached the lactate clearance group whereas much more of the groups (35 vs 24) reached the urine output goal. This is more reason to make me wonder how useful lactate clearance is. A secondary outcome of mortality at 28 days, although NOT statistically significant was interestingly was a 6% difference (15.5 vs 21.9) in favor of the early norepi group. THIS METRIC IS DEFINITELY SOMETHING I’D LIKE TO SEE REPEATED IN A US STUDY AS THE PRIMARY OUTCOME. Another 5% mortality is impressive. 20% is what is typical of all the other sepsis trials (ARISE, PROMISE, etc.) with sick patients showed, so that would be impressive if early norepi could decrease this subsets mortality. The last interesting point is that there was no statistical difference in limb or organ ischemia between the two groups and half of the patients had only peripheral lines. These patients were in the hospital for a median of 10 days. It would be nice to know how long the patients had the norepi running. Also, many of these patients were admitted to the wards and NOT the ICU (about 50% of both groups). These two facts in addition to all the other literature on peripheral pressor’s really makes me feel better about running norepi peripherally. However that fact that this was based in a lower resource country with admissions criteria that are different also make it not as generalizable.  So does this change practice? That waits to be seen, however, I have always felt that dumping in the magical 30ml/kg into a patient who is not hemorrhaging to be missing the point. I am biased toward giving early pressors…