Posts tagged #resuscitation

Review of the ATHOS 3 trial

**Written by:** Saabir Kaskar, MD (NUEM ‘23) **Edited by:** Amanda Randolph, MD (NUEM ‘20)
**Expert Commentary by**: Matt McCauley, MD (NUEM’ 21)

Review of the ATHOS 3 Trial: Angiotensin II for the Treatment of Vasodilatory Shock

Angiotensin, first isolated in the late 1930s, in recent years has become the new innovative vasopressor used in intensive care units, a change driven largely by the results of the ATHOS-3 trial. The ATHOS-3 trial in 2017 explored the efficacy of angiotensin II as a vasopressor for severe vasodilatory shock. Severe shock is defined as persistent hypotension requiring vasopressors to maintain a mean arterial pressure of 65mmHg and serum lactate <2 despite adequate volume resuscitation. Two classes of vasopressors have been used in the past for hypotension. They are catecholamines and vasopressin-like peptides. The human body, however, employs a third class which is angiotensin. Angiotensin II is an octapeptide hormone and a potent vasopressor that is an integral component of the renin-angiotensin-aldosterone system. It works by activating the ANGII type 1 receptor which subsequently activates a G coupled protein pathway and phospholipase C, thereby inducing vasoconstriction.

The ATHOS-3 trial compared the efficacy and safety of angiotensin II versus placebo in catecholamine-resistant hypotension, which is defined as an inadequate response to standard doses of vasopressors. The study was designed as a phase III multicenter randomized placebo control trial taking place across 75 intensive care units in the United States from 2015 to 2017. The three main inclusion criteria were catecholamine-resistant hypotension (defined as >0.2ug/kg/min of norepinephrine or equivalent for 6-48 hours to maintain a MAP 55-70 mmHg), adequate volume resuscitation (25mL/kg of crystalloid), and features of vasodilatory shock (mixed venous O2 >70% and CVP >8mmHg or cardiac index >2.3 L/min/m2).

Patients in vasodilatory shock that met the criteria of catecholamine-resistant hypotension were randomized to treatment with angiotensin II or placebo. Angiotensin II was initiated at an infusion rate of 20ng/kg/min and adjusted during the first three hours to increase MAP to at least 75mmHg. The primary outcome of the study was the response in MAP three hours after the start of angiotensin II infusion. A response was deemed as a MAP increase of 10mmHg from baseline or a MAP over 75mmHg without an increase in baseline vasopressor infusions. During the first three hours, the angiotensin II group had a significantly greater increase in MAP than placebo (12.5mmHg vs 2.9 mmHg). Angiotensin II also allowed for rapid increases in MAP which permitted decreases in doses of baseline catecholamine vasopressor. Additionally, improvement in the cardiovascular SOFA score was significantly greater in the angiotensin II group than in the placebo group. However, the overall SOFA score did not differ between groups. Rates of adverse events such as tachyarrhythmias, distal ischemia, ventricular tachycardia, and atrial fibrillation were similar in the angiotensin II and placebo groups. Overall serious adverse events that included infectious, cardiac, respiratory, gastrointestinal, or neurologic events were reported in 60.7% of patients who received angiotensin II and 67.1% of patients who received placebo.

The strengths and limitations of the ATHOS 3 trial are critical to how its author’s conclusions should be interpreted. The strengths of the study include that it was a randomized double-blind control trial examining a new class of vasopressor for refractory vasodilatory shock. Refractory shock is a common condition with high mortality, and so the investigation of an additional treatment modality can be of great clinical impact. However, one limitation of the study was that it was underpowered to demonstrate a mortality difference. It showed improvement in blood pressure which is a clinically important parameter but not a patient-oriented outcome. Interestingly, when vasopressin was studied in 2008, it similarly did not show a mortality benefit when added to norepinephrine infusion in septic shock2. It did, however, show a decrease in norepinephrine dosing which parallels the findings of the ATHOS 3 trial.

An additional point of contention with the ATHOS 3 trial is that the manuscript does not report an increase in thrombotic risk. It has been shown that angiotensin II increases thrombin formation and impairs thrombolysis3. The FDA even reports angiotensin II has a risk for thrombosis as there was a higher incidence (13% vs 5%) of arterial and venous thrombotic events in the angiotensin II vs placebo group in the ATHOS 3 trial itself. For this reason, the FDA recommends concurrent VTE prophylaxis with the use of angiotensin II. Further data regarding the thrombotic risk of angiotensin II would be helpful to determine which patient populations the vasopressor should be avoided in.

Overall, the author’s conclusion in the ATHOS 3 trial is that angiotensin II increased blood pressure in patients with a vasodilatory shock that did not respond to high doses of conventional vasopressors. It has been shown to raise mean arterial pressure over 75 mm Hg or by an increase of 10 mm Hg within three hours. The ATHOS 3 trial, however, did not demonstrate a mortality benefit when using angiotensin II. Further studies are needed to elucidate whether Angiotensin II truly improves patient outcomes in vasodilatory shock.

Expert Commentary

Thank you for this great summary of the ATHOS 3 trial. While this trial paved the way for the clinical use of angiotensin II as a vasopressor, you’ve raised some salient points as to why we should approach this emerging intervention with skepticism. The biggest shortcoming in my mind is the primary outcome of the study; it’s not particularly impressive that a vasopressor resulted in higher blood pressures compared to a placebo. Mortality benefit is an extremely elusive goal in critical care research1 but that doesn’t discount the fact that ATHOS 3 wasn’t designed to demonstrate an improvement in any patient-oriented outcome. ICU length of stay, hospital length of stay, ventilator-dependent days, or rate of renal replacement therapy: these are all things that matter to our patients and to our health systems and they are more fruitful targets when we investigate interventions.

There’s been some study of angiotensin II in the years since it has landed in our hospital formularies and there has not been robust data supporting its use. Some of the most recent data come from a multi-center retrospective study that includes patients from Northwestern. This review of 270 patients receiving angiotensin II demonstrated that 67% of patients were able to maintain a MAP of 65 with stable or reduced vasopressor doses. Univariate analysis showed that these patients that responded did have a statistically significant mortality benefit over the patients deemed nonresponders (41% vs 25%)2. If we are going to find a benefit of this drug, further study predicting which patients will be responders is necessary but this study did note that patients already receiving vasopressin and those with lower lactates (6.5 vs 9.5) were more likely to respond. Outside of septic shock, there is interest in the use of angiotensin II in refractory vasoplegia associated with post-cardiac surgery3 and anti-hypertensive overdose4. These are, of course, only hypothesis-generating.

But what does that mean to us clinically in the ED and ICU? This data shows us that angiotensin II can make the blood pressure better but I would never let it distract you from the things we know matter in sepsis resuscitation. Source control timely antibiotics, rational fluid resuscitation, and ruling out other causes of vasopressor refractory shock to include anaphylaxis, hemorrhage, adrenal insufficiency, LVOT obstruction, and any other cause of cardiogenic shock need to be ruled out and addressed. In my personal practice, I make sure to optimize these and start vasopressin shortly after the initiation of norepinephrine. In a patient already on vaso that has stopped responding to escalating doses of norepinephrine, I reach for my ultrasound probe and reassure myself that there isn’t significant sepsis-related myocardial dysfunction because those patients may benefit from a trial of an inotrope like epinephrine. In those with a good cardiac squeeze, I think it’s appropriate to discuss with your intensivist and clinical pharmacist the utility of adding angiotensin II as part of a kitchen-sink approach. Until we have more data about the benefits of this extremely expensive intervention, I wouldn’t lose sleep if you’re unable to secure it for your patient.

References

Chawla LS et al. Intravenous Angiotensin II for the Treatment of High-Output Shock (ATHOS Trial): A Pilot Study. Crit Care 2014; 18(5): 534. PMID: 25286986
Russell JA et al. Vasopressin Versus Norepinephrine Infusion in Patients with Septic Shock. NEJM 2008; 358(9): 877 – 87. PMID: 18305265
Celi A et al. Angiotensin II, Tissue Factor and the Thrombotic Paradox of Hypertension. Expert Review of Cardiovascular Therapy 2010; 8(12): 1723-9 PMID: 21108554
Santacruz CA, Pereira AJ, Celis E, Vincent JL. Which Multicenter Randomized Controlled Trials in Critical Care Medicine Have Shown Reduced Mortality? A Systematic Review. Crit Care Med. 2019;47(12):1680-1691. doi:10.1097/CCM.0000000000004000
Wieruszewski PM, Wittwer ED, Kashani KB, et al. Angiotensin II Infusion for Shock: A Multicenter Study of Postmarketing Use. Chest. 2021;159(2):596-605. doi:10.1016/j.chest.2020.08.2074
Papazisi O, Palmen M, Danser AHJ. The Use of Angiotensin II for the Treatment of Post-cardiopulmonary Bypass Vasoplegia. Cardiovasc Drugs Ther. Published online October 21, 2020. doi:10.1007/s10557-020-07098-3
Carpenter JE, Murray BP, Saghafi R, et al. Successful Treatment of Antihypertensive Overdose Using Intravenous Angiotensin II. J Emerg Med. 2019;57(3):339-344. doi:10.1016/j.jemermed.2019.05.027

Matt McCauley, MD

How To Cite This Post:

[Peer-Reviewed, Web Publication] Kaskar, S. Randolph, A. (2022, Feb 14). Review of ATHOS 3 trial. [NUEM Blog. Expert Commentary by McCauley, M]. Retrieved from http://www.nuemblog.com/blog/review-athos3-trial.

Resuscitative Hysterotomy

**Written by:** Aldo Gonzalez, MD (NUEM ‘23) **Edited by:** Justine Ko, MD (NUEM ‘21)
**Expert Commentary by**: Paul Trinquero, MD (NUEM '19) & Pietro Bortoletto, MD

Introduction

Resuscitative hysterotomy (RH) is the new term for what was previously called perimortem cesarean delivery (PMCD). The new nomenclature is being adopted to highlight the importance of the procedure to a successful resuscitation during maternal cardiopulmonary arrest (MCPA). It is defined as the procedure of delivering a fetus from a gravid mother through an incision in the abdomen during or after MCPA. The goal of the procedure is to improve the survival of the mother and the neonate.

Physiology

There are physiologic changes that occur during pregnancy which reduce the probability of return of spontaneous circulation (ROSC) during cardiac arrest. Physiologic anemia of pregnancy reduces the oxygen carrying capacity of blood and results in decreased delivery of oxygen during resuscitation. The large gravid uterus elevates the diaphragm and reduces the lung’s functional reserve capacity (FRC), which when combined with increased oxygen demand from the fetus results in decreased oxygen reserves and resultant risk for rapid oxygen desaturations. The size of a gravid uterus at 20 weeks results in aortocaval compression which reduces the amount of venous return from the inferior vena cava and reduces cardiac output during resuscitation. The theory behind resuscitative hysterotomy is to increase the probability of ROSC by reducing the impact of aortocaval compression.

Supporting Evidence

A 2012 systematic review primarily investigated the neonatal and maternal survival rates after perimortem cesarean delivery and secondarily attempted to evaluate maternal and fetal neurological outcome and the ability to perform the procedure within the recommended time frame.

Inclusion Criteria

original articles, case series, case reports and letters to the editor, and reports from databases
had minimum of least five clinical details of the case (e.g. patient age, gravidity, parity, obstetric history, medical history, presenting rhythm, or location of arrest)
AND
the care administered (chest compression, ventilation, monitoring, drug administration)
AND
maternal return of spontaneous circulation or survival to hospital discharge or fetal neonatal outcome

Exclusion Criteria

Post-delivery arrests
Studies without enough data to understand the details of the arrests
Studies with unclear maternal and fetal outcomes

Population

Pregnant woman that
- (1) had a cardiac arrest or a non-perfusing rhythm
- (2) received chest compression and/or advanced life support medications and/or defibrillation
Average maternal age: 30.5±6.5 years (median 32, range 17–44, IQR, 26.5–35.5, n = 80)
Gravidity: 2.5±1.5 (median 2, range 1–7, IQR 1–4, n = 59)
Parity: 1.1±1.3 (median 1, range 0–6, IQR 0–2, n = 57)
Singleton Pregnancies: 90.4% (n = 85)
Average gestational age at arrest: 33±7 weeks (median 35, range 10–42, IQR 31–39, n = 85)

Results

for cases undergoing PMCD, earlier time from arrest to delivery was associated with increased survival (p < 0.001, 95%CI 6.9–18.2)
- surviving mothers: 27/57; 10.0±7.2 min (median 9, range 1–37)
- non-surviving mother: 30/57; 22.6±13.3 min (median 20, range 4–60)]
for neonates delivered by PMCD/RH earlier time from arrest to delivery was associated with increased survival (p = 0.016)
- surviving neonates: 14±11 min (median = 10, range = 1–47)
- non-survivor neonates: 22±13 min (median = 20, range = 4–60)
Only 4 cases met the timeframe of less than minutes

Take-Aways: Performing a PMCD/RH in the 4-5 minutes time frame is difficult. However, PMCD/RH beyond the proposed time is still beneficial and earlier time to delivery from arrest is associated with better outcomes

Guideline Recommendations

Perform basic life support (BLS) in the same way as non-pregnant patients

Place patient in supine position
- Left lateral decubitus (left lateral tilt) positioning is no longer recommended during compressions because of reduced efficacy of chest compressions
No modification of Chest compressions
- Rate: 100-120 per minute
- Depth: at least 2 inches (5 cm)
- Allow for full chest recoil between compressions
- Avoid interruptions as much as possible
No modification of Ventilation
- Use bag-ventilation
- Compression to breath ratio: 30:2 before advanced airway

Perform advanced cardiac life support (ACLS) as in non-pregnant women

No modification of Ventilation
- Once breath every 6 seconds (10 BPM) with advanced airway
No modification of medications
- Use 1 mg Epinephrine of epinephrine every 3-5 minutes
No modification to defibrillation
- Use adhesive pads on patient
- Place in anterolateral position
  - Lateral pad should be placed under breast tissue
- Defibrillate for Ventricular fibrillation or Ventricular tachycardia
- Use usual Voltages
  - Biphasic: 120-200 Joules
- Resume compressions after shock is delivered

Special considerations during resuscitation

Obtain access above the diaphragm to minimize the effect of aortocaval compression on the administration of drugs
Perform left uterine deviation during resuscitation to reduce aortocaval compression
If a gravid patient suffers a cardiac arrest mobilize resources to prepare for the need for resuscitative hysterotomy and the resuscitation of the fetus early

Palpate the size of the gravid uterus
- If above the height of the umbilicus then patient is most likely greater than 20 weeks gravid and a candidate for RH
Strongly consider performing RH (PMCD) if the patient does not achieve ROSC by the 4-minute mark and qualified staff to perform the procedure are present
Aim to have the procedure done by the 5-minute mark
Consider performing RH (PMCD) sooner if maternal prognosis is poor or prolonged period of pulselessness
RH should be performed at the site of the resuscitation
Do not delay procedure to prepare abdomen
- May pour iodine solution over abdomen prior to incision
Do not delay procedure for surgical equipment if scalpel is available
Continue performing LUD while performing RH

Figure 1: One-handed left uterine deviation technique

Figure 2: Two-handed left uterine deviation technique

Steps for Resuscitative Hysterectomy

Pre-procedure

Gather supplies to perform RH
- Personal Protective Equipment
  - Gloves
  - Face mask
  - Apron/gown
- Resuscitative Hysterotomy Equipment
  - Scalpel(the minimum equipment to perform procedure)
  - Blunted Scissors
  - Clamps/Hemostats
  - Gauze
  - Suction
  - Large absorbable sutures
  - Needle Holder
  - Antiseptic Solution
- Neonatal resuscitation equipment
  - Dry Linens
  - Neonatal Bag Valve Mask
  - Neonatal Airway supplies
  - Suction
  - Umbilical venous access equipment
  - Neonatal resuscitation drugs
  - Baby Warmer
  - Plastic Bag
Form teams to perform Resuscitative Hysterotomy
- Resuscitative Team
- Resuscitative Hysterotomy Team
- Neonatal Resuscitation Team

Procedure

Maintain patient in supine position and continue compressions
Continue Left Uterine Deviation until the start of incision
Quickly prepare the skin with antiseptic solution (do not delay for skin prep)
Perform midline vertical Incision with scalpel on the abdomen from pubic symphysis to umbilicus and cut through skin and subcutaneous tissue until fascia is reached
Use fingers to bluntly dissect the rectus muscle fascia access the peritoneum (can use scalpel or blunt scissors)
Locate the uterus and differentiate it from the bladder (bladder yellow and enveloped in fatty tissue)
Make a vertical incision from the lower uterus to the fundus with scalpel (can use blunt scissors)
If the placenta is encountered while entering the uterus, cut through it
Use a cupped hand to locate the fetal part closest to pelvis
Elevate the located fetal part and pass through uterine incision while applying transabdominal pressure with other hand
Use traction and transabdominal pressure to deliver the rest of the baby
Clamp the cord at two spots and cut in between both clamps
Hand the baby to the neonatal team
Deliver placenta with gentle traction

Post-procedure

Continue performing compressions
Consider stopping if ROSC not achieved after several rounds and depending on the cause of PMCA
Give medications to promote uterine contraction
Analgesia and sedation may be required if patient achieves ROSC
Bleeding will be worse if ROSC achieved and may require pharmacologic and nonpharmacologic interventions
Closure will depend on whether the patient achieves ROSC and may necessitate careful closure to prevent further bleeding. Best performed by an obstetrician. If an obstetrician is unavailable, pack the uterus with gauze and clamps actively bleeding vessels to reduce bleeding.
Administer prophylactic antibiotics

References

Einav, S., et al. (2012). "Maternal cardiac arrest and perimortem caesarean delivery: evidence or expert-based?" Resuscitation 83(10): 1191-1200.
Jeejeebhoy, F. M., et al. (2015). "Cardiac Arrest in Pregnancy: A Scientific Statement From the American Heart Association." Circulation 132(18): 1747-1773.
Kikuchi, J. and S. Deering (2018). "Cardiac arrest in pregnancy." Semin Perinatol 42(1): 33-38.
Parry, R., et al. (2016). "Perimortem caesarean section." Emerg Med J 33(3): 224-229.
Rose, C. H., et al. (2015). "Challenging the 4- to 5-minute rule: from perimortem cesarean to resuscitative hysterotomy." Am J Obstet Gynecol 213(5): 653-656, 653 e651.
Soskin, P. N. and J. Yu (2019). "Resuscitation of the Pregnant Patient." Emerg Med Clin North Am 37(2): 351-363.
Walls, R. M., et al. (2018). Rosen's emergency medicine: concepts and clinical practice. Philadelphia, PA, Elsevier.

Expert Commentary

This is an excellent review of an extremely rare, but potentially life-saving procedure. It may seem daunting to perform (and it should), but the evidence would say that a resuscitative hysterotomy (RH), especially if performed promptly, drastically improves survival during the catastrophic scenario of maternal cardiac arrest. This is even more important because these patients are young (and often relatively healthy) and could potentially have decades of meaningful quality of life if they can survive the arrest. That being said, this procedure is so rare that most of us not only have never performed it, but often have never even seen it. Not only that, but unlike other rare lifesaving procedures (such as cricothyroidotomy or resuscitative thoracotomy), RH is extremely difficult to practice in cadaver labs due to the unavailability of pregnant cadavers. So, we are left with the next best thing: familiarizing ourselves with the anatomy, physiology, and simplified technique of the procedure and mentally rehearsing it so that when the time comes, we can be ready.

For these rare procedures, in addition to the excellent and thorough review above, it is also helpful to simplify and rehearse the fundamental steps. I’m not an obstetrician and certainly not an expert on this procedure, but I’ve mentally prepared myself for what I would do in the event that I am faced with this grave situation and categorized it into the following simplified five step plan. Also, prior to writing this commentary I got a curbside consult from a friend from med school and actual obstetrician and gynecologic surgeon, Dr. Pietro Bortoletto.

First off, the indications-- basically, a pregnant woman estimated to be >20 weeks EGA who has suffered a cardiac arrest. Don’t worry about the 4 minutes, make the decision to perform a RH right away and start prepping. Delegate someone to call the appropriate resuscitation teams if available. Then start the procedure.

Step 1: Setup. You probably don’t have a c section kit in your trauma bay, so instead open the thoracotomy tray and you’ll have most of what you need. Go ahead and set aside the finochietto rib spreaders so that you don’t have a panic attack trying to remember how to put those together with other people watching. But everything else you’ll need will be in that tray (basically a scalpel, blunt scissors, and hemostats).

Step 2: Cut into the Abdomen. Splash prep the abdomen with betadine. Then make your long vertical incision from the uterine fundus to the pubic symphysis. Cut through the skin and subcutaneous tissue then bluntly separate the rectus and enter the peritoneum with scalpel or blunt scissors. Extend the peritoneal incision with blunt scissors.

Step 3: (carefully) Cut into the Uterus. First, locate the uterus. Then, take a deep breath and remember that there is a fetus inside the uterus. With that terrifying thought in mind, cut vertically into the uterus, insert your fingers, and extend the incision upwards with blunt scissors and a steady hand. If you encounter an anterior placenta, cut right through it.

Step 4: Delivery. Deliver the fetus either by cupping the head and elevating it through the incision or by grabbing a leg, wiggling out the shoulders, and then flexing the head. Hand over the neonate to whoever is taking the lead on the neonatal resuscitation (will need to be warmed, stimulated, and potentially aggressively resuscitated). Clamp and cut the cord, leaving a long enough umbilical stump for an easy umbilical line if needed. Then using gentle traction, attempt delivery of the placenta. If it isn’t coming easily, leave it alone so as not to stir up more bleeding.

Step 5: Extra credit. If you’ve made it this far as an emergency physician and there is still no obstetrician in sight, you can continue resuscitation, focusing on stopping the uterine bleeding. While you don’t need to close the fascia or skin, it can be helpful to close the uterine incision to prevent additional blood loss. You can do this with a whip stitch using 0-0 vicryl (or if that seems like showing off, you can just pack it with sterile gauze. If you’ve got it handy, give 10 IU oxytocin to stimulate uterine contraction and further slow bleeding. Feel free to order some antibiotics as well. Otherwise, continue maternal resuscitation following typical ACLS.

The big picture here is that this is a heroic, potentially life-saving procedure that most of us will never do. But we can all take a few minutes to read an excellent review like the blog post above, watch a video, and mentally walk ourselves through the simplified steps. That preparation will afford us some much-needed confidence if we are ever faced with this terrifying scenario.

Paul Trinquero, MD

Medical Director

Department of Emergency Medicine

US Air Force Hospital - Langley

Pietro Bortoletto, MD

Clinical Fellow

Reproductive Endocrinology & Infertility

Weill Cornell Medical College

How To Cite This Post:

[Peer-Reviewed, Web Publication] Gonzalez, A. Ko, J. (2021, Dec 13). Resuscitative Hysterotomy. [NUEM Blog. Expert Commentary by Trinquero, P and Bortoletto, P]. Retrieved from http://www.nuemblog.com/blog/resuscitative-hysterotomy.

Bicarb in Cardiac Arrest

**Written by:** Kishan Ughreja, MD (NUEM ‘23) **Edited by:** Sean Watts, MD (NUEM ‘22)
**Expert Commentary by**: Dana Loke, MD (NUEM ‘21)

Utility of Sodium Bicarbonate in Cardiac Arrest

Use of sodium bicarbonate as empiric therapy in cardiac arrest has been an area of controversy. During cardiac arrest hypoxia and hypoperfusion results in severe metabolic acidosis and subsequent impaired myocardial contractility, decreased efficacy of vasopressors, and increased risk of dysrhythmias. Previous ACLS guidelines recommended use of sodium bicarbonate to mitigate these effects; however, harms are also associated with its routine use including compensatory respiratory acidosis, hyperosmolarity, increased vascular resistance, and reduction in ionized calcium. 1 Current guidelines no longer recommend routine use of sodium bicarbonate, except in cases of arrest secondary to hyperkalemia, TCA overdose or preexisting metabolic acidosis.2 Regardless of these recommendations, sodium bicarbonate continues to be utilized during routine management of cardiac arrest, and studies are limited in investigating its appropriate use.

The study below investigates the effect of sodium bicarbonate in patients suffering out-of-hospital cardiac arrest with severe metabolic acidosis during prolonged CPR.

Article

Clinical Question

In patients with prolonged, atraumatic out-of-hospital cardiac arrest (OHCA) and severe metabolic acidosis, does sodium bicarbonate (SB) administration with transient hyperventilation improve acidosis without increased CO2 burden, enhance rates of return of spontaneous circulation (ROSC), survival to admission, and favorable neurologic outcomes?

Study Design

Double-blind, prospective, randomized, placebo-controlled, single-center pilot clinical trial

Population

Inclusion criteria: Atraumatic arrest in patients ≥18yo without ROSC after 10 minutes of CPR in ED and with pH <7.1 or bicarbonate <10 mEq/L on ABG

Exclusion criteria: DNR, ECPR, ROSC w/i 10 minutes of ACLS, absence of severe metabolic acidosis on ABG after 10 minutes of CPR

Data collection over 1 year at Asan Medical Center, a tertiary referral center in Seoul, Korea

Intervention

Sodium bicarbonate administration of 50 mEq/L over 2 minutes with concurrent increase in ventilation rate from 10 to 20 breaths per minute for 2 minutes

Control

Normal saline administration of 50 mL over 2 minutes (with same transient hyperventilation)

Outcomes

Primary

Change in acidosis (per methods section)

Secondary

Sustained ROSC — defined as restoration of a palpable pulse ≥20 min (per methods section, but listed as primary outcome in abstract)
Survival to hospital admission
Good neurological survival at 1 and 6 months (defined as cerebral performance category 1 or 2)

Results

157 patients presented with cardiac arrest, 50 enrolled per inclusion criteria
No significant differences between study and control groups regarding demographics, PMH, witnessed arrest, bystander CPR, pre-hospital and initial cardiac rhythm
10% (n=5) of enrolled patients with sustained ROSC and admitted
No patients survived at 6 months follow up

Pre-Intervention

ABG results at 10 minutes were not significantly different between groups

Post-intervention

ABG results at 20 minutes demonstrate that pH and HCO3- were higher in the study group than in the control group
- pH 6.99 vs 6.90, p=0.038
- HCO3- 21.0 vs 8.00, p=0.007
Within the study group, the increase in pH was not statistically significant after sodium bicarbonate administration; the increase in HCO3- was statistically significant (using Wilcoxon signed rank test)
No statistically significant findings in the control group after normal saline administration
No significant differences in any secondary outcomes (sustained ROSC, survival to admission, good neurologic outcome)

Strengths

Randomized, double-blinded, placebo-controlled study design
This study adds additional information to a clinical question that has limited previous research
This study added a practical clinical intervention (hyperventilation) to counteract excessive CO2 accumulation secondary to sodium bicarbonate administration, a known deleterious effect of this compound.
Strong control over sodium bicarbonate administration (no pre-hospital administration allowed in South Korea), so authors could control when it was given and analyze ABG results at desired intervals)

Weaknesses

Small, single-center study with only 50 enrolled patients
Primary endpoint unclear from abstract vs methods, whether it was change acidosis or sustained ROSC; however, neither is truly patient-centered clinical outcome (good neurological outcome would be the ideal primary outcome)
Dosing was universal — 50 mEq/L instead of weight based (1-2 mEq/L/kg), which could result in improper dosing
Hyperventilation strategy may have benefited sodium bicarbonate administration group by countering respiratory alkalosis, however, it could have harmed the placebo group
Possible venous sampling rather than arterial for blood gas analysis at 10-minute point, though this would be a concern in any arrest setting if an arterial line could not be established in this time frame

Author’s Conclusion

“The use of sodium bicarbonate during CPR with transient hyperventilation improves acid-base status without CO2 elevation which is one of the most concerned adverse effects of sodium bicarbonate administration, but it had no effect on the improvement of the rate of ROSC and good neurologic survival. At this point, we could not advise for or against its administration, our pilot data could be used to help design a larger trial to verify the efficacy of sodium bicarbonate.”

Bottom Line

Based on this study, the use of sodium bicarbonate does not appear to improve clinically significant outcomes, though it improved acid-base status. Sodium bicarbonate should not be indiscriminately used in all cardiac arrests, and larger trials should be performed to further evaluate its impact on patient-centered outcomes.

Citation

Ahn, S., Kim, Y. J., Sohn, C. H., Seo, D. W., Lim, K. S., Donnino, M. W., & Kim, W. Y. (2018). Sodium bicarbonate on severe metabolic acidosis during prolonged cardiopulmonary resuscitation: a double-blind, randomized, placebo-controlled pilot study. Journal of thoracic disease, 10(4), 2295.

References

White, S. J., Himes, D., Rouhani, M., & Slovis, C. M. (2001). Selected controversies in cardiopulmonary resuscitation. Seminars in respiratory and critical care medicine, 22(1), 35–50. https://doi.org/10.1055/s-2001-13839
Merchant, R. M., Topjian, A. A., Panchal, A. R., Cheng, A., Aziz, K., Berg, K. M., Lavonas, E. J., Magid, D. J., & Adult Basic and Advanced Life Support, Pediatric Basic and Advanced Life Support, Neonatal Life Support, Resuscitation Education Science, and Systems of Care Writing Groups (2020). Part 1: Executive Summary: 2020 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Circulation, 142(16_suppl_2), S337–S357. https://doi.org/10.1161/CIR.0000000000000918

Expert Commentary

Thank you Dr. Ughreja and Dr. Watts for this excellent blog post on an important topic. In medicine, we often ask “what else can we do?” but less often do we ask “is what we’re already doing effective?” This is especially important for resuscitation and cardiac arrest. Not everything that is standard-of-care is ultimately effective care, and overtreating patients can lead to other untoward effects.

In addition to the points made in the above blog, I would add a few important notes into the equation. First, the study excluded in-hospital cardiac arrest and therefore should not be considered in those patients. Second, the study also excluded those patients with early ROSC and absence of severe metabolic acidosis, effectively biasing towards inclusion of sicker patients. It is unclear how administration of sodium bicarbonate may have influenced those patients. Third, the study population was quite small and a striking majority of that population were found to have an initial rhythm of asystole. Fourth, ventilation rates were purposefully increased during bicarb administration. Though this may be practical and can potentially counteract excessive CO2 accumulation secondary to sodium bicarbonate administration, this is not common practice which leads to questions of this study’s external validity at other institutions.

So, despite this study, at this point in time we still must grapple with the “should-we-or-should-we-not” of sodium bicarbonate administration in prolonged cardiac arrest. Some scenarios certainly do require sodium bicarbonate, most notably TCA overdose and hyperkalemia. In these cases, it’s obvious what to do. But so often what we do in emergency medicine is riddled with uncertainty. An unclear cause of cardiac arrest is certainly one of those situations. Perhaps instead of mindlessly giving sodium bicarbonate to cardiac arrest patients, we should give it once or twice and look for evidence that it has had an effect. Is the rhythm narrowing? Did you obtain ROSC shortly after administration? If not, giving dose after dose of sodium bicarbonate in hopes of meaningful recovery may not be the best path forward.

Dana Loke, MD

Department of Emergency Medicine

Northwestern University Feinberg School of Medicine

Northwestern Memorial Hospital

How To Cite This Post:

[Peer-Reviewed, Web Publication] Ughreja, K. Watts, S. (2021, Dec 6). Bicarb in Cardiac Arrest. [NUEM Blog. Expert Commentary by Loke, D]. Retrieved from http://www.nuemblog.com/blog/bicarb-arrest

Basic Capnography Interpretation

Written by: Shawn Luo, MD (NUEM ‘22) Edited by: Matt McCauley, MD (NUEM ‘21) Expert Commentary by: N. Seth Trueger, MD, MPH — **Written by:** Shawn Luo, MD (NUEM ‘22) **Edited by:** Matt McCauley, MD (NUEM ‘21) **Expert Commentary by**: N. Seth Trueger, MD, MPH

Continuous waveform capnography has increasingly become the gold standard of ETT placement confirmation. However, capnography can provide additional valuable information, especially when managing critically ill or mechanically ventilated patients.

Normal Capnography

Phase I (inspiratory baseline) reflects inspired air, which is normally devoid of CO2.
Phase II (expiratory upstroke) is the transition between dead space to alveolar gas.
Phase III is the alveolar plateau. Traditionally, PCO2 of the last alveolar gas sampled at the airway opening is called the EtCO2. (normally 35-45 mmHg)
Phase 0 is the inspiratory downstroke, the beginning of the next inspiration

EtCO2 is only one component of capnography. Measured at the end-peak of each waveform, it reflects alveolar CO2 content and is affected by alveolar ventilation, pulmonary perfusion, and CO2 production.

Figure 2. Factors affecting ETCO2 (EMSWorld)

EtCO2 - PaCO2 Correlation

Correlating EtCO2 and PaCO2 can be problematic, but in general, PaCO2 is almost always HIGHER than EtCO2. Normally the difference should be 2-5mmHg but the PaCO2-EtCO2 gradient is often increased due to increased alveolar dead space (high V/Q ratio), such as low cardiac output, cardiac arrest, pulmonary embolism, high PEEP ventilation.

Important Patterns

Let’s go through a few cases and learn some of the important capnography waveforms to recognize

Case 1: Capnography with Advanced Airway

An elderly gentleman with a history of COPD, CAD & CKD gets rushed into the trauma bay with respiratory distress and altered mental status. You gave him a trial of BiPAP for a few minutes without improvement.

You swiftly tubed the patient. It was not the easiest view, but you advance the ETT hoping for the best. Upon attaching the BVM to bag the patient, you saw this on capnography:

Oops, the ETT is in the esophagus, as evidenced by the low-level EtCO2 that quickly tapers off.

2. You remove the ETT, bag the patient up, and try again with a bougie. Afterward, you see…

Figure 4. Capnography with ETT in right main bronchus (EMSWorld)

This suggests a problem with ETT position, most often in the right main bronchus. Notice the irregular plateau--the initial right lung ventilation, followed by CO2 escaping from the left lung. Beware that capnography can sometimes still appear normal despite the right main bronchus placement.

3. You pull back the ETT a few cm and the CXR now confirms the tip is now above the carina. The patient’s capnography now looks like this:

Figure 5. Capnography showing obstruction or bronchospasm (SketchyMedicine)

Almost looks normal but notice the “shark fin” appearance, this is due to delayed exhalation, often seen in airway obstruction and bronchospasms such as COPD or asthma exacerbation.

4. You suction the patient and administer several bronchodilator nebs. The waveform now looks more normal:

Figure 6. Capnography showing normal waveform (SketchyMedicine)

5. However, just as you were about to get back to the workstation to call the ICU, the monitor alarms and you see this:

Figure 7. Sudden loss of capnography waveform (SketchyMedical)

Noticing the ETT still in place with good chest rise, you quickly check for a pulse. There is none.

6. You holler, push the code button and start ACLS with a team of clinicians. With CPR in progress, you notice this capnography:

Figure 8. Capnography during CPR (SketchyMedicine)

Initially, your patient’s EtCO2 was only 7, after coaching the compressor and improving CPR techniques, it increased to 14.

You are also aware that EtCO2 at 20min of CPR has prognostic values. EtCO2 <10 mmHg at 20 minutes suggests little chance of achieving ROSC and can be used as an adjunctive data point in the decision to terminate resuscitation.

7. Fortunate for your patient, during the 3rd round of ACLS, you notice the following:

Figure 9. ROSC on capnography (emDOCs.net)

This sudden jump in EtCO2 suggests ROSC. You stop the CPR and confirm that the patient indeed has a pulse.

8. As you are putting in orders for post-resuscitation care, you notice this:

Figure 10. Asynchronous breathing on capnography (SketchyMedical)

This curare cleft comes from the patient inhaling in between ventilator-delivered breaths and is usually a sign of asynchronous breathing. However, in the post-arrest scenario, it is a positive prognostic sign as your patient is breathing spontaneously. You excitedly call your mom, I meant MICU, about the incredible save.

Case 2: Capnography with Non-intubated Patient

You just hung up the phone with MICU when EMS brings you a young woman with a heroin overdose. She already received some intranasal Narcan from EMS but per EMS report patient is becoming sleepy again.

She mumbles a little as you shout her name, and as you put an end-tidal nasal cannula on her, you saw this:

Figure 11. Hypoventilation on capnography (emDOCs.net)

Noticing the low respiratory rate and high EtCO2 value, you recognize this is hypoventilation.

2. But very soon she becomes even less responsive and the waveform changed again:

Figure 12. Airway obstruction on capnography (emDOCs.net)

The inconsistent, interrupted breaths suggest airway obstruction, while the segments without waveform suggest apnea. You have to act fast.

3. By then your nurse has already secured an IV, so you pushed some Narcan. However, in the heat of the moment, you gave the whole syringe. The patient quickly woke up crying and shaking.

Figure 13. Hyperventilating on capnography (emDOCs.net)

She was quite upset and hyperventilating. The waveform reveals a high respiratory rate and relatively low EtCO2.

As much as you are a little embarrassed by putting the patient into florid withdrawal, you know it could have been a lot worse. Walking away from the shift, you think about how many times capnography has assisted you during those critical moments. “Hey, perhaps we should buy a capnography instead of a baby monitor,” you ask your wife at dinner.

Additional Resources

This website provides a tutorial and quiz on some of the basic capnography waveforms.

References

American Heart Association. 2019 American Heart Association Focused Update on Advanced Cardiovascular Life Support. Circulation. 2019; 140(24). https://doi.org/10.1161/CIR.0000000000000732
Brit Long. Interpreting Waveform Capnography: Pearls and Pitfalls. emDOCs.net. www.emdocs.net/interpreting-waveform-capnography-pearls-and-pitfalls/, accessed May 12, 2020
Capnography.com, accessed May 12, 2020
Kodali BS. Capnography outside the operating rooms. Anesthesiology. 2013 Jan;118(1):192-201. PMID: 23221867.
Long, Koyfman & Vivirito. Capnography in the Emergency Department: A Review of Uses, Waveforms, and Limitations. Clinical Reviews in Emergency Medicine. 2017; 53(6). https://doi.org/10.1016/j.jemermed.2017.08.026
Nassar & Schmidt, Capnography During Critical Illness. CHEST. 2016; 249(2). https://doi.org/10.1378/chest.15-1369
Sketchymedicine.com/2016/08/waveform-capnography, accessed May 13, 2020
Wampler, D. A. Capnography as a Clinical Tool. EMS World. www.emsworld.com/article/10287447/capnography-clinical-tool. June 28, 2011. Accessed May 13, 2020

Expert Commentary

This is a nice review of many of the intermediate and qualitative uses of ETCO2 in the ED. For novices, I recommend a few basic places to start:

Confirmation of intubation. Color change is good but it’s just litmus paper and gets easily defeated by vomit. Also, in low output states, it may not pick up. Further, colorimetric capnographs require persistent change over 6 breaths, not just a single change. Waveform capnography uses mass spec or IR spec to detect CO2 molecules. There are so many uses, it’s good to have, I don’t see why some are resistant to use this better plastic adapter connected to the monitor vs the other, worse, plastic adapter.

a. The mistake I have seen here is assuming a lack of waveform is due to low cardiac output, ie there’s no waveform because the patient is being coded, not because of esophageal intubation. There is always *some* CO2 coming out if there is effective CPR; if there isn’t, the tube is in the wrong place. If you really don’t believe it, check with good VL but a flatline = esophagus.

2. Procedural sedation. There’s lots of good work and some debate about absolute or relative CO2 changes or qualitative waveform changes that might predict impending apnea, but for me, the best use is that I can just glance at the monitor for a second or two and see yes, the patient is breathing. No more staring at the chest debating whether I see chest rise, etc. It’s like supervising a junior trainee during laryngoscopy with VL: it’s anxiolysis for me.

a. Using ketamine? Chest movement or other signs of respiratory effort without ETCO2 waveform means laryngospasm. Jaw thrust, bag, succinylcholine (stop when better).

3. Cardiac arrest.

a. Quality of CPR. Higher number means more output. Can mean the compressor needs to fix their technique, or more often, is tiring out and needs a swap.

b. ROSC. There can be a big jump (eg from 15 to 40) when ROSC occurs. Very helpful.

c. Ending a code. 20 mins into a code, if it’s <10 during good CPR, the patient is unlikely to survive. I try to view this as confirming what we know – it’s time to end the code. The mistake here is to not end a code that should otherwise end because the ETCO2 is above 10; it doesn’t work like that, it’s a 1-way test.

4. Leak. One waveform shape I wanted to add that I find helpful: if the downstroke kinda dribbles down like a messy staircase, it’s a leak. Can be an incomplete connection (eg tubing to the vent) or the balloon is too empty or full.

Seth Trueger, MD, MPH

Assistant Professor of Emergency Medicine

Department of Emergency Medicine

Northwestern University

How To Cite This Post:

[Peer-Reviewed, Web Publication] Luo, S., McCauley M. (2021, Sept 9). Basic Capnography Interpretation. [NUEM Blog. Expert Commentary by Trueger N.S]. Retrieved from http://www.nuemblog.com/blog/capnography

Preterm Neonatal Resuscitation

Peterm Neonatal Resuscitation Blog_1.jpg

Expert Commentary

Thanks to Dr. Wibberley and Dr. Eswaran for providing this infographic on a tough topic – neonatal resuscitations.

Usually, deliveries in the emergency department cause a dichotomy of emotions – initial anxiety, then relief and happiness. Most of our deliveries tend to be quick, precipitous, with hopefully just enough warning for us to grab gloves and remember where the baby warmer is. Unfortunately, when babies decide to struggle with their first few minutes of life, this becomes a lot more stressful for everyone.

Fair warning – though I am an emergency medicine physician, and prepared to deal with emergent situations of any age, I think there are very few of us who feel as comfortable with neonatal resuscitations as we do with critically ill trauma or cardiac arrest patients. Especially if your department sees very little pediatrics, it is completely normal to feel anxiety when imagining resuscitating a neonate, and even more so a pre-term baby. This is OK! In fact, this should motivate you to get familiar with NRP, and provides a perfect opportunity for spaced repetition throughout your career to enhance recall.

Here are my broad strokes steps for a fresh neonate requiring resuscitation.

#1: Know your resources! The first step in managing a neonatal resuscitation occurs far before the patient shows up in your department. Where is your baby warmer? Where are your teeny-tiny BVM’s? What’s the smallest ETT and intubating blade you stock, and where? I promise you, the hardest part of intubating this baby won’t be the actual mechanics of placing an ETT – it will be in the preparation and supply gathering. Don’t rely on your nurses to know everything when seconds count – know where this stuff is yourself.

#2: Call for help, early and often. Many emergency departments have some type of OB/imminent delivery response – hopefully this brings in a pediatrician well trained in neonatal resuscitation as well. Hopefully, this also brings a nurse who is used to placing IV’s in these itty bitty babies. If this doesn’t describe your hospital, call to start the transfer process, and move on to #3…

#3: Dry and stim. Nearly all babies respond to drying and stimulation. Please don’t start bagging a poor newborn before drying it off and giving it a good rub for 30-60 seconds (unless it’s extremely pre-term – try to avoid rubbing all the skin off of a 25-weeker, this is bad form.) At the same time, keep in mind that these babies will need some form of external thermoregulation so make sure the warmer is actually functioning.

#4: When in doubt, fix the breathing. As is obvious when scanning through NRP guidelines, 95% of managing a sick newborn lies in assisting the respirations. Poor tone? Fix the breathing. Initial HR below 100? Try to fix the breathing. Poor color? You get it. Don’t be afraid to escalate from blow by, to PEEP, to BVM. If the baby has little to no respiratory effort, a couple initial breaths via BVM can quickly improve the situation. But please, when you’re bagging a tiny neonate, use small breaths – this is not the typical 120 kg patient we are used to.

#5: In the short term, an IO is your friend. A UVC is golden, but not really possible in an active resuscitation. The good news is that most babies don’t need IV access in the short term – for my reasoning, see #3 and #4. The literature suggests that placing the neonatal IO in the proximal tibia, distal tibia, or distal femur can be safe and effective.

#6: This is the time to debrief. Whether a happy or a tragic ending, this is a rare and emotional event in the emergency department. Debrief with your team. Talk to whoever you talk to about this stuff – spouse, friend, coworker. We are champions of compartmentalization in the emergency department out of necessity, but don’t bear the entirety of these encounters on yourself – lean on those around you.

Spenser Lang, MD

Assistant Professor

Department of Emergency Medicine

University of Cincinnati

How To Cite This Post:

[Peer-Reviewed, Web Publication] Wibberly, A. Eswaran, V. (2020, Nov 9). Preterm Neonatal Resuscitation. [NUEM Blog. Expert Commentary by Lang, S]. Retrieved from http://www.nuemblog.com/preterm-neonatal-resuscitation

Approach to Hypothermic Resuscitation

Screen Shot 2018-05-31 at 11.50.30 AM.png

Written by: Luke Neil, MD (NUEM PGY-2) Edited by: Quentin Rueter, MD, (NUEM PGY-4) Expert commentary by: Kory Gebhardt, MD

Expert Commentary

This is a good overview of the algorithmic approach to the hypothermic patient. Generally speaking, hypothermia can be divided into various categories of severity, but as you mention, it is really those patients with a core temperature of <32°C (90°F) with cardiac instability or cardiac arrest that will require especially aggressive care.

For any hypothermic patient, the most important initial intervention is to stop any further heat loss. This is especially important for those with damp or wet clothing. Any wet garments should be completely removed, the patient should be dried, and then covered with warm, dry blankets and possibly a forced air rewarming device (i.e. Bair Hugger). Recall that one of the most efficient ways to cool a HYPERthermic patient is with evaporative cooling (spraying with or submerging them in water and then using fans to circulate air over the wet surfaces). Similarly, this heat loss will strongly work against you in rewarming a hypothermic patient if they are not fully dry. After this simple intervention, the majority of mildly hypothermic and stable patients just need time to bring their core temperature back to normal and often can be discharged once this has occurred.

For those patients with a core temp >32°C with severe cardiac instability or in cardiac arrest, you should also consider alternative etiologies for their presentation rather than expect it solely caused by the hypothermia alone. Like you mention, if you are able to rewarm a cardiac arrest patient above this temperature and they remain in asystole, it is likely that irreversible damage has occurred and they are less likely to be able to be successfully resuscitated.

As you detail in the algorithm, those with a temperature less than 32°C (90°F) AND instability or arrest need aggressive and invasive rewarming. The best available means of doing this is ECMO. Much of the research surrounding accidental hypothermia and resuscitation comes from the Nordic countries where freezing temperatures are often combined with outdoor extracurriculars and results in a high “n” for the studies. Outcomes data from many of the expert centers in this area show major benefits of ECMO, including one showing survival post-arrest in nearly 60% of patients and, even more importantly, good neurologic outcomes in 38% compared to only 3% in those without extracorporeal rewarming!

Unfortunately, not all EM physicians will have quick or 24/7 availability of ECMO. While this should be the preferred means of rewarming if available, there are alternatives if it is not. Hemodialysis circuits can also be used to actively rewarm a patient. Generally these can achieve 2-4 degrees/hr of rewarming compared to the 4-6 degrees/hr of ECMO. Thoracic (bilateral chest tubes), gastric (NG tube), and bladder lavage (foley) with warm fluids can also provide several degrees per hour of rewarming if used appropriately. Use a ventilator that can warm and humidify air. Don’t forget about minimizing heat loss by fully drying the patient and keeping as much of them covered as possible.

Lastly, I want to say a word about prognostication. While the mantra is, “you’re not dead until you’re warm and dead”, you can imagine that these patients require a considerable amount of time, effort, and mobilization of resources when they present to the ED. There is information that can help guide which patients are likely to benefit from such aggressive care from those who are, unfortunately, unlikely to be resuscitated. While multiple markers have been studied, the one with the most evidence supporting it, is a potassium value. This value can serve as a sort of surrogate for “warm ischemia time”, or in other words, how long were they warm and dead. This should be obtained and sent early in the resuscitation of the patient. If the value is >12, there is nearly no chance of any meaningful recovery (still very unlikely at >10, and even a cutoff of >8). Conversely, if the potassium level is less than the 8-12 range, the patient still has a good chance at a meaningful recovery if resuscitated to ROSC and these are the patients that should receive everything we have to rapidly and efficiently rewarm them (they are also the patients that can have meaningful recoveries despite impressive downtimes of even hours).

Additionally, historical factors surrounding the hypothermia, if known, can provide valuable prognostic information. Immersion vs. Submersion, which you define in your algorithm, is one example that might influence your decision about whether a patient might have benefit from mobilizing ECMO or other aggressive/invasive rewarming.

Screen Shot 2018-05-31 at 11.29.58 AM.png

Kory Gebhardt, MD

Kaiser Permanente Emergency Medicine

How to cite this post

[Peer-Reviewed, Web Publication] Neil L, Rueter Q (2018, June 4 ). Approach to Hypothermic Resuscitation. [NUEM Blog. Expert Commentary by Gebhardt K]. Retrieved from http://www.nuemblog.com/blog/hypothermia

Posted on June 4, 2018 by NUEM Blog and filed under Cardiovascular and tagged hypothermia resuscitation cardiac arrest rewarming bair hugger.

Review of the ATHOS 3 trial