Study Design

Reduced Quality Factors

0 = no serious, - = serious,

- - = very serious

Positive Quality Factors

0 = none, + = one, ++ = multiple

Dichotomous Outcome Summary

Non-Dichotomous Outcome Summary

Brief description

Overall Quality

High, moderate, low,
very low, none

No of studies

Study Type

RoB

Indirectness

Imprecision

Inconsistency

Large Effect

Dose-Response

Confounder

# Intervention with Outcome

# Control with Outcome

RR (95% CI)

Outcome: Favorable neurologic outcome

3

OB

0

- -

0

-

0

0

0

Very low

Outcome: Survival to discharge

3

OB

0

- -

0

0

0

0

0

Very low

Outcome: ROSC

12

OB

0

- -

0

0

0

0

0

Very low

1

EX

0

-

-

0

0

0

0

Very low

Introduction

While it has been established that higher ETCO2 values are associated with better outcomes in CPR in people, the minimum ETCO2 target in dogs and cats is unknown.1 Hofmeister et al. (2009) reported that in their population of dogs, 17 of 18 (94%) with an ETCO2 < 15 mm Hg during CPR were not successfully resuscitated, whereas 25 of 29 (86%) with a ETCO2 ≥ 15 mm Hg achieved ROSC.2ofJ In the same study, 5 of 9 cats with a ETCO2 < 20 mm Hg were not successfully resuscitated, whereas 9 of 10 cats with a ETCO2 ≥ 20 mm Hg achieved ROSC. The best way to use ETCO2 to improve chest compression technique in dogs and cats is unknown.

Consensus on science

Outcome 1: Favorable neurologic outcome

For the most critical outcome of FNO, 3 observational studies in people (very low quality of evidence, downgraded for very serious indirectness and inconsistency) were identified that addressed the PICO question. In 803 adults with IHCA, Sutton (2016) found that ETCO2 > 10 mmHg during CPR was significantly associated with FNO compared to people with ETCO2 ≤ 10 mmHg (OR 2.31, CI95 1.31, 4.09; P = 0.004).3 Calbay (2019) found no association between continuous ETCO2 value during CPR and FNO in 155 adults with OHCA.4 Finally, in 43 pediatric patients with IHCA, Berg et al (2018) found that all children who survived to discharge did so with a FNO, and that both survivors and non-survivors achieved median ETCO2 values > 20 mm Hg during CPR.5

Outcome 2: Survival to discharge

For the next most critical outcome of survival to discharge, we identified 3 observational studies in people (very low quality of evidence, downgraded for very serious indirectness) that address the PICO question. In 803 adults with IHCA, Sutton (2016) found that ETCO2 > 10 mmHg during CPR was associated with survival to hospital discharge compared to patients with ETCO2 ≤ 10 mmHg (OR 2.41, CI95 1.35, 4.30; P = 0.003).3 A prospective, observational study in 102 adults undergoing CPR in the emergency department found that median ETCO2 during CPR was higher (35 mmHg) in patients that survived to hospital admission than in nonsurvivors (13.7 mmHg, P < 0.01); ETCO2 > 16 mmHg predicted survival to hospital admission.6 In 43 pediatric patients with IHCA, Berg et al. (2018) found no difference in survival to discharge when comparing pediatric patients with mean ETCO2 > 20 mmHg to those with lower mean ETCO2 during CPR.5

Outcome 3: ROSC

For the next critical outcome of ROSC, 12 observational studies (very low quality of evidence, downgraded for very serious indirectness)5,7–17 and 1 experimental study in dogs (very low quality of evidence, downgraded for serious indirectness and imprecision)18 were identified that address the PICO question.

Observational clinical veterinary studies:

In a registry study of 109 dogs and cats undergoing CPR, median ETCO2 was significantly higher (23 mmHg) in those that achieved ROSC than in those that did not (15 mmHg; P = 0.0004); ETCO2 of 16.5 mmHg was recommended as the cutoff to maximize likelihood of ROSC (sensitivity 75%, CI95 60%, 86%; specificity 64%, CI95 52%,75%).7 One clinical observational study in 35 dogs and cats undergoing CPR found that patients that achieved ROSC had significantly higher initial (P = 0.0083), peak (P < 0.0001), mean (P < 0.0001), and change in (P = 0.0004) ETCO2 than patients that did not achieve ROSC; optimal ETCO2 cutoff to predict ROSC was 18 mmHg.8

Observational clinical human studies of 100 people or more:

A prospective, observational study in 737 adults with OHCA found that ETCO2 at 20 minutes into ALS was higher in patients that achieved ROSC (32.8 mmHg ± 9.1 mmHg) than in those that did not (6.9 ± 2.2 mmHg; P < 0.001).11 One observational study in 575 adults with OHCA found that mean ETCO2 was higher in patients with ROSC than in those that did not achieve ROSC, regardless of cause of arrest or arrest rhythm.17 One prospective observational study of 114 adults with OHCA found significantly higher ETCO2 from 5 minutes into CPR to the final value obtained in people achieving ROSC than in those who did not, regardless of cause of arrest.16 Finally, Singer (2018) described an optimal ETCO2 target of ≥ 19 mm Hg based on the prospective observational study of 100 adult human patients with OHCA.13

Observational clinical human studies of 99 people or fewer:

An observational study in 97 adults with IHCA or OHCA found that the final ETCO2 (36.4±4.46 mm Hg vs 11.74±7.01 mm Hg; P < 0.05) and the difference between initial and final ETCO2 (P < 0.05) were different between patients that achieved ROSC and those that did not.12 An observational study of OHCA in 90 adults found that people who achieved ROSC had significantly higher ETCO2 just prior to ROSC (31 ± 5.3 mmHg) than those who did not achieve ROSC by 20 minutes into ALS (3.9 ± 2.8 mmHg).14 Savastano (2017) evaluated defibrillation success of 207 defibrillation events in 62 people with OHCA in shockable rhythms and determined that a higher ETCO2 was associated with defibrillation success (P = 0.003; P for trend < 0.001); no shocks administered to patients with ETCO2 > 45 mm Hg were unsuccessful.10 Finally, a study in 32 young to middle-aged adults suffering non-traumatic OHCA or IHCA found that mean ETCO2 during CPR was lower in those who failed to achieve ROSC (19.1 ± 7.8 mm Hg) than in those that achieved ROSC (26.3 ± 6.5 mm Hg; P = 0.01).9

Only 2 identified studies found a lack of association between ETCO2 and ROSC, including one in a small population of adults15 and one in pediatrics.5

Experimental study in target species:

Finally, an experimental study in dogs supported the relationship of higher ETCO2 with ROSC, however showed much lower mean ETCO2 in the survivor group than reported in other studies (9.6 +/- 3.2 mm Hg).18

Treatment recommendation

We recommend optimizing CPR to maximize ETCO2 to no less than 18 mmHg in dogs and cats undergoing CPR. (strong recommendation, very low quality of evidence)

Justification of treatment recommendation

Observational veterinary and human studies, in addition to some experimental data, suggest that higher ETCO2 targets are positively correlated with ROSC. There was no direct comparison identified of 15 mm Hg versus higher ETCO2 values, which was the specific PICO question. Therefore, this recommendation is to target the high value found in clinical observational studies of dogs and cats (ETCO2 > 18 mm Hg), with the understanding that as a concept, higher ETCO2s into the low 30s in mm Hg are associated with ROSC in observational studies of people.

Knowledge gaps

Optimal ETCO2 targets in dogs and cats undergoing CPR are unknown, and larger studies are warranted. The effects of precise targets, and the collateral damage (ie. more damage to thoracic structures) that may occur with more aggressive CPR to achieve higher ETCO2 raises questions about how high an ETCO2 is too high, or if such a value exists.