Article, Cardiology

Is pulseless electrical activity a reason to refuse cardiopulmonary resuscitation with ECMO support?

a b s t r a c t

Background: Cardiopulmonary resuscitation with ECMO support (ECPR) has shown to improve outcome in pa- tients after cardiac arrest under resuscitation. Most current recommendations for ECPR do not include patients with a non-shockable rhythm such as PEA and asystole.

Aim: The aim of this study was to investigate the outcome of 3 patient groups separated by initial rhythm at time of ECMO placement during CPR: asystole, PEA and shockable rhythm.

Methods: We made a retrospective single-center study of adults who underwent ECPR for in-hospital cardiac ar- rest between June 2008 and January 2017. Outcome and survival were identified in 3 groups of patients regarding to the heart rhythm at the time decision for ECMO support was made: 1. patients with asystole, 2. patients with pulseless electrical activity, 3. patients with a shockable rhythm.

Result: 63 patients underwent ECPR in the mentioned time frame. Five patients were excluded due to incomplete data. Under the 58 included patients the number of cases for asystole, PEA, shockable rhythm was 7, 21 and 30 respectively. The means of CPR-time in these groups were 37, 41 and 37 min. Survival to discharge was 0.0%, 23.8% and 40.0% respectively (p = 0.09). All survivors to discharge had a good neurological outcome, defined as cerebral performance category 1or 2.

Conclusion: Survival to discharge in patients with PEA as initial rhythm at the time of decision for ECPR is 23.8% while no patients with asystole as initial rhythm survived discharge. Patients with PEA should be carefully con- sidered for ECPR.

(C) 2017

Introduction

Using veno-arterial extracorporeal membrane oxygenation (VA- ECMO) during resuscitation (ECPR) improves the outcome in a certain type of patients after refractory cardiac arrest [1] and also became a pos- sible procedure in the emergency department [2].

It remains unclear which patients benefit from this invasive and costly procedure and therefore ECPR has also significant ethical implica- tions [3] and patient selection is important. While ECPR on patients with refractory cardiac arrest and ventricular fibrillation has shown higher survival rates comparing to conventional cardiopulmonary resuscita- tion (C-CPR) [4], the role of ECPR in patients with non-shockable rhythm remains unclear. Many programs exclude patients with asystole and PEA from consideration for ECPR due to very limited outcome after conventional CPR [5-6] in both of these groups, PEA and asystole.

* Corresponding author at: Heart and Vascular Institute, Penn State Milton S. Hershey Medical Center, 500 University Drive, Hershey, PA, 17033-0850, USA.

E-mail address: [email protected] (D. Pabst).

Meaney PA et al. could show in a study with more than 50,000 adult pa- tients with cardiac arrest and mechanical CPR that survival to discharge was slightly more likely after PEA than asystole (12% vs 11%) [6]. How- ever, data for outcome of patients with PEA and asystole who underwent ECPR are still rare and to our knowledge direct comparing of these two patient-groups has not be publicized yet.

Reasons for PEA are various include reversible diseases like hypovo- lemia, tachydysrhythmias, cardiomyopathy, pulmonary embolism, car- diac tamponade, Tension pneumothorax, and electrolyte abnormalities [7]. The absence of mechanical contractions is caused by factors that de- plete myocyte high-energy phosphate stores and inhibit myocardial fiber shortening, which include metabolic acidosis and ionic perturba- tions, particularly potassium and calcium changes [8]. These reversible conditions might be diagnosed and treated better by giving more time through VA-ECMO support. Therefore we hypothesize that under ECPR patients with PEA have a better outcome than patients with asystole.

We investigated in a single-center study the outcome of patients who underwent ECPR and compared 3 groups of patients regarding to

https://doi.org/10.1016/j.ajem.2017.09.057

0735-6757/(C) 2017

the rhythm at the time when decision for ECPR was made: asystole, PEA and shockable rhythm (ventricular fibrillation or ventricular tachycardia).

Methods

Study design

This is a retrospective, single-center study.

Data collection and setting

The patients studied included 63 patients who underwent VA-ECMO placement for resuscitation after cardiac arrest between June 2008 and January 2017 in the Penn State Milton S. Hershey Medical Center. Five patients were excluded from the study due to incomplete data. Informa- tion were received through the “Cerner Health Facts(R) database” (Cerner Corporation, Kansas City, MO). Clinical and demographic vari- ables included age, sex, BMI, maximal level of creatinine, lactate, LDH, bilirubin, ALT prior to ECMO, maximal and minimal level of sodium, po- tassium, calcium, phosphate, magnesium and maximal troponine level as well as minimum ionized calcium, and bicarbonate during the first 24 h after ECPR. Reasons for cardiogenic shock were compiled. The SOFA (Sepsis-related Organ Failure Assessment) scores were calculated 24 h after CPR was started.

Patient categories

The total of 58 patients were stratified into 3 categories by the heart rhythm at time of decision for VA-ECMO was made (asystole, PEA, shockable rhythm (ventricle fibrillation (VF) or pulseless ventricle tachycardia (VT)).

ECPR treatment and patient management

Preparation for ECPR was started when mechanical CPR did not lead to return of spontaneous circulation (ROSC) within the first 10 min. All patients were under mechanical CPR by the time ECMO was placed.

Mechanical CPR was performed in accordance to the ACLS guidelines of the American Heart Association prior and during ECMO placement.

The ECMO circuit consisted of a Quadrox(R) oxygenator (Maquet Car- diovascular; Wayne, NJ) and a centrifugal pump, either a Centrimag(R) pump (Levitronix LLC, Waltham, MA) or a Rotaflow pump (Maquet Car- diovascular, Wayne, NJ).

The ECMO cannulation was performed by the attending intensivists. A peripheral catheter placement in both the femoral artery and the fem- oral vein by percutaneous Seldinger technic was done in the vast major- ity of the patients. ECMO management and care of the patient was performed by our Heart and Vascular Institute Critical Care Unit (HVICCU) team. Epinephrine, milrinone or dobutamine were used as

inotropes. ECMO flows were adjusted appropriately to maintain mean arterial pressures (MAP) of more than 65 mm Hg and arterial saturation of more than 93%.

“Target temperature management” (TTM) was used in the majority of patients after cardiac arrest and a goal temperature of 32-34 ?C for 24 h was aimed.

Study endpoint

The primary endpoint was survival to discharge. The secondary end- point was requirement for renal replacement therapy and neurological outcome.

The Cerebral Performance Category was used to describe the neurological status. CPC 1 and 2 were defined as good neurological outcome.

Statistical analysis

We de-identified the patients and recorded clinical and laboratory data.

We used the IBM SPSS Statistics Version 24 (IBM Corporation, Armonk, NY) for statistical analyses. The Pearson’s x2 test of indepen- dence or the Fisher’s exact test and the Kruskal-Wallis test (for non-nor- mal distributions) were used to compare data between the 3 different Rhythm groups. Statistical significance was defined by a p-value of

0.05 or less. We established a Kaplan-Meier survival curve to show sur-

vival difference in the 3 patient groups. We reported the results as per- centages, means +- standard deviations, and/or medians and interquartile ranges (IQRs).

Results

Patients characteristics

The characteristics of the patients divided by the initial heart rhythm at time of decision making for ECMO treatment are shown in Table 1. There was no significant difference between the 3 groups in age, gender, BMI, maximal lactate, maximal troponine, maximal LDH, bilirubin and ALT. A significant difference of the creatinine level, maximum and min- imum potassium level and low magnesium level between the groups could be found, with the highest and lowest mean level respectively in the PEA group. Furthermore another significant variable was the per- centage of patients with acute myocardial infarction as origin for cardio- genic shock, with the highest percentage (76.7%) within the group with shockable rhythm and the lowest percentage (38.1%) under the patients with PEA. Other reasons for cardiogenic shock were not significantly dif- ferent between the groups. Duration of CPR and SOFA score also did not differ significantly.

A “target temperature management” (TTM) with a goal temperature

of 32-34 ?C for 24 h was performed in 30 patients (50.9%).

Table 1

Characteristics of patients after ECPR (n = 58).

Variables

Total cases (n = 58)

Asystole (n = 7)

PEA (n = 21)

Shockable rhythm (n = 30)

p-Value

Age (mean, years)

56.59 (+-15.11)

52.14 (+-18.05)

58.95 (+-13.19)

55.97 (+-15.88)

0.622

Male (n, %)

36 (62.1)

3 (42.9)

13 (65.0)

20 (66.7)

0.490

BMI

32.39(+- 10.75)

33.26 (+-4.33)

33.43 (+-14.53)

31.46 (+-8.71)

0.592

Reason for shock; n(%) aMI

36 (62.1)

5 (71.4)

8 (38.1)

23 (76.7)

0.017

cardiomyopathy (no aMI)

2 (3.4)

0 (0)

1 (4.8)

1 (3.3)

0.835

Pulmonary embolism

4 (6.9)

0 (0)

3 (14.3)

1 (3.3)

0.235

Allograft rejection

5 (8.6)

0 (0)

3 (14.3)

2 (6.7)

0.436

Septic shock

3 (5.2)

0 (0)

3 (14.3)

0 (0)

0.062

Complication procedure

7 (12.1)

1 (14.3)

3 (14.3)

3 (10.0)

0.882

Duration of CPR (min)

38.9 (+-17.9)

36.6 (+-18.0)

41.1 (+-15.2)

37.2 (+-21.4)

0.712

SOFA

13.63 (2.51)

14.75 (2.22)

14.00 (3.04)

12.93 (1.90)

0.363

D. Pabst, C.E. Brehm / American Journal of Emergency Medicine 36 (2018) 637640 639

Outcome

The results of a univariate analysis comparing the relationship be- tween the 3 different groups and outcome are shown in Table 2. Surviv- al to discharge rate was 0.0% for patient with asystole, 23.8% for patients with PEA, 40.0% for patients with a shockable rhythm. Fig. 1 shows a Kaplan-Meier-survival curve of the three groups. There was no signifi- cant difference in the numbers of ICU-days, days on device and days on ventilator between the 3 groups. The need for continuous renal re- placement therapy (CRRT) was significantly different, with the highest number in the PEA-group and the lowest number in the patient-group with asystole.

Discussion

Principal finding

The study shows that although there was no significant difference in the survival rate between the groups, a remarkable better survival was seen in patients with a shockable rhythm. This was expected due to known significant differences between shockable rhythm and non- shockable rhythm in bigger studies [6]. However, we also saw a remark- able trend toward improved survival in the PEA group when compared with the asystole group.

The reason for PEA can be various acutely reversible disorders in- cluding hypovolemia, tachydysrhythmias, cardiomyopathy, pulmonary embolism, cardiac tamponade and electrolyte abnormalities [7].

We found a significant higher median level for creatinine, maximal potassium as well as minimum potassium and magnesium level in the patient group with PEA, pointing that electrolyte abnormalities might have been played an important role in this group of patients. VA- ECMO support could prolong the time for diagnostic and treatment. Es- pecially this patient group might benefit from this time gain and give providers a better chance to resolve the electrolyte abnormalities. The need for Continuous renal replacement therapy in the PEA group was also significantly higher.

To our knowledge this is the only study that compares outcome of ECPR patients with PEA and ECPR patients with asystole. Bigger studies are necessary to confirm or deny our hypothesis that patients with PEA have a better outcome than patients with asystole under ECPR.

If our hypothesis would be correct the outcome in patients with PEA under resuscitation with VA-ECMO should be significantly higher than in patients with asystole since this group of patients would be given

Fig. 1. Kaplan-Meier one-year survival curve of 58 ECPR patients.

more time to diagnose and treat the disorder leading to PEA. Because of the limited time of resuscitation in the pre-ECPR era patients with PEA were not given the time needed to treat these reversible disorders. Therefore patients with PEA during resuscitation should be included if considering ECPR.

In our study we even had a significantly lower amount of acute myo- cardial infarction in the PEA group since these patients often present with a shockable rhythm as initial rhythm in cardiac arrest.

Limitations

This study is a retrospective, single center study. The number of 58 patients might be too small to show a significant difference between the outcome of patients with asystole and patients with PEA under ECPR.

Conclusion

This study did show a non-significant difference in discharge to sur- vival between patients under ECPR with asystole on the one side and patients with PEA on the other side.

Table 2

Results after ECPR (n = 58 patients).

Total

Asystole

PEA

Shockable rhythm

P

Discharge n/N (%)

17 (29.3)

0 (0)

5 (23.8)

12 (40.0)

0.088

ICU days

15.31 (24.10)

7.00 (11.83)

15.90 (23.25)

16.93 (26.88)

0.274

Days on device

6.55 (7.08)

6.14 (11.87)

6.43 (6.16)

6.73 (6.56)

0.389

ventilator days

9.61 (13.26)

7.00 (11.73)

8.72 (9.65)

10.79 (15.59)

0.267

CRRT

29 (50.0)

1 (14.3)

15 (71.4)

13 (43.3)

0.019

Creatinine

1.87 (+-1.01)

1.60 (+-0.71)

2.51(+-1.01)

1.50 (+-0.89)

0.003

Troponine

117.35(+-187.47)

161.0 (+-258.4)

46.6 (+-97.9)

130.2 (+-179.9)

0.226

Lactate

11.19 (+-5.46)

13.00 (+-5.49)

12.71 (+-5.18)

9.59 (+-5.39)

0.120

LDH

5383 (+-4137)

7079 (+-4375)

6667 (+-5083)

3996 (+-2770)

0.200

Bilirubin

1.42 (+-1.15)

1.82 (+-1.61)

1.61 (+-1.39)

1.19 (+-0.77)

0.566

Na (max level) mmol/l

146.4 (8.9)

152.0 (7.6)

144.1 (9.6)

146.7 (8.3)

0.095

Na (min level) mmol/l

135.9 (7.6)

138.6 (9.4)

134.8 (5.5)

136.0 (8.5)

0.203

K (max level) mmol/l

5.2 (1.3)

5.1 (1.2)

5.8 (1.4)

4.8 (1.0)

0.050

K (min level) mmol/l

3.3 (0.9)

3.1 (1.0)

3.8 (1.0)

3.0 (0.6)

0.005

Mg (max level) mmol/l

2.8 (1.2)

3.1 (0.8)

2.5 (0.8)

2.9 (1.5)

0.223

Mg (min level) mmol/l

2.1 (0.5)

2.5 (0.8)

2.1 (0.4)

2.0 (0.4)

0.258

Ca (min level) mmol/l

7.5 (1.1)

7.9 (0.9)

7.5 (1.2)

7.5 (1.1)

0.429

Ion Ca (min level) mmol/l

0.95 (0.24)

1.02 (0.14)

0.88 (0.27)

0.97 (0.24)

0.623

Bicarbonate (min level)

15.8 (4.6)

16.3 (3.5)

15.2 (4.0)

16.0 (5.3)

0.867

Phosphate (max) mmol/l

7.26 (3.77)

7.30 (4.94)

9.02 (3.18)

5.90 (3.44)

0.026

Phosphate (min) mmol/l

4.22 (2.59)

3.97 (4.28)

4.35 (1.29)

4.19 (2.89)

0.260

We have seen a significant higher number of patients with electro- lyte abnormalities and need for CRRT in the group with PEA patients. Reversible diseases could have caused cardiac arrest in many of these cases.

Lager studies are needed to clarify if patients with PEA have a signif- icant better outcome after resuscitation with ECPR than patients with asystole. In patients with asystole ECPR does not seem to be a reason- able option for resuscitation.

Grant numbers and/or funding information. None.

Conflict of interest

None declared.

References

  1. Chen YS, Lin JW, HY Yu, Ko WJ, Jerng JS, Chang WT, et al. Cardiopulmonary resuscita- tion with assisted extracorporeal life-support versus conventional cardiopulmonary resuscitation in adults with in-hospital cardiac arrest: an observational study and pro- pensity analysis. Lancet 2008 Aug 16;372(9638):554-61. https://doi.org/10.1016/ S0140-6736(08)60958-7 [Epub 2008 Jul 4].
  2. Bellezzo JM, Shinar Z, Davis DP, Jaski BE, Chillcott S, Stahovich M. et Emergency phy- sician-initiated extracorporeal cardiopulmonary resuscitation. Resuscitation 2012 Aug;83(8):966-70. https://doi.org/10.1016/j.resuscitation.2012.01.027 [Epub 2012 Feb 1].
  3. Tramm R, Ilic D, Davies AR, Pellegrino VA, Romero L, Hodgson C. Extracorporeal mem- brane oxygenation for critically ill adults. Cochrane Database Syst Rev 2015 Jan 22; 1:CD010381. https://doi.org/10.1002/14651858.CD010381.pub2.
  4. Siao FY, Chiu CC, Chiu CW, Chen YC, Chen YL, Hsieh YK, et al. Managing cardiac arrest with refractory ventricular fibrillation in the emergency department: conventional cardiopulmonary resuscitation versus extracorporeal cardiopulmonary resuscitation. Resuscitation 2015 Jul;92:70-6. https://doi.org/10.1016/j.resuscitation.2015.04.016 [Epub 2015 Apr 29].
  5. Andrew E, Nehme Z, Lijovic M, Bernard S, Smith K. Outcomes following out-of-hospi- tal cardiac arrest with an initial cardiac rhythm of asystole or pulseless electrical ac- tivity in Victoria, Australia. Resuscitation 2014 Nov;85(11):1633-9. https://doi.org/ 10.1016/j.resuscitation.2014.07.015 [Epub 2014 Aug 7].
  6. Meaney PA, Nadkarni VM, Kern KB, Indik JH, Halperin HR, Berg RA. Rhythms and out- comes of adult in-hospital cardiac arrest. Crit Care Med 2010 Jan;38(1):101-8. https://doi.org/10.1097/CCM.0b013e3181b43282.
  7. Mehta C, Brady W. Pulseless electrical activity in cardiac arrest: Electrocardiographic presentations and Management considerations based on the electrocardiogram. Am J Emerg Med 2012 Jan;30(1):236-9. https://doi.org/10.1016/j.ajem.2010.08.017 [Epub 2010 Oct 20].
  8. Paradis NA, Martin GB, Goetting MG, et al. aortic pressure during human cardiac ar- rest. Identification of pseudo-electromechanical dissociation. Chest 1992;101:123-8.

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