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

2

Obs

-

--

-

0

0

0

0

Very low

Outcome: Suvival to discharge

4

Obs

-

--

-

0

0

0

0

Very low

Outcome: ROSC

4

Exp

-

-

0

0

0

0

0

Low

3

Obs

-

--

-

0

0

0

0

Very low

Introduction

Atropine, a parasympatholytic, is recommended to prevent CPA in patients with bradycardia secondary to high vagal tone. The RECOVER 2012 guidelines also suggest that it can be considered during CPR in dogs and cats with non-shockable arrest rhythms, particularly in animals with high vagal tone as a suspected trigger for arrest.1 However, atropine has been removed from human CPR guidelines, and the evidence is primarily supportive of atropine as part of treatment of bradycardia, rather than as part of CPR. This question investigates whether atropine is beneficial in dogs and cats with high vagal tone preceding CPA.

Consensus on science

Outcome 1: Favorable neurologic outcome

There are 2 retrospective observational studies of humans with non-shockable arrest rhythms (very low quality of evidence, downgraded for serious risk of bias and very serious indirectness), neither of which showed an association between atropine administration and favorable neurologic outcome.2,3

Outcome 2: Survival to discharge

A total of 4 retrospective observational studies of humans with non-shockable arrest rhythms (very low quality of evidence, downgraded for serious risk of bias and very serious indirectness) examined the association of atropine administration with survival to discharge. The 2 previously mentioned studies showed no association between atropine administration and this outcome. 2,3 One of the additional studies showed an association between atropine administration and reduced likelihood of survival to discharge using a multi-variate analysis for in-hospital CPA (odds ratio 0.21, 95% CI 0.055 – 0.81).4 The other study showed a survival to discharge benefit associated with administration of epinephrine and/or atropine, but did not examine the effects of the 2 drugs independently.5

Outcome 3: ROSC

Four experimental animal studies in dogs were identified that examined the outcome of ROSC (low quality of evidence, downgraded for serious risk of bias and serious inconsistency). The most direct evidence involved an asphyxial PEA arrest model in 75 dogs that received chest compressions, epinephrine every 3 minutes, and a single injection of one of four doses of atropine or placebo.6 Dogs receiving standard dose atropine (0.04 mg/kg IV) had comparable ROSC rates to dogs receiving placebo. ROSC rates were lower for dogs receiving higher doses of atropine (0.1, 0.2, and 0.4 mg/kg IV). In another experimental study of 40 dogs with induced asphyxia arrests leading to PEA treated with chest compressions and ventilation, dogs receiving an alpha-adrenergic agonist had significantly higher ROSC rates than dogs given saline placebo, but dogs treated with atropine or calcium chloride had similar ROSC rates to placebo controls.7 However, a study of PEA induced by asphyxia in dogs showed that dogs receiving epinephrine and atropine (0.025mg/kg IV) had higher rates of ROSC than dogs receiving epinephrine and D5W (10/11 vs 8/12, P < 0.01).8 Finally, in a study of bradycardic arrests induced in dogs using digoxin and propranolol, administration of atropine prior to the arrest prevented CPA.9

Three retrospective observational studies in people with non-shockable arrest rhythms (very low quality of evidence, downgraded for serious risk of bias and very serious indirectness) examined the association of atropine with ROSC.2–4 Of these, only one showed an association with increased ROSC in patients with asystole (odds ration 1.6, 95% CI 1.4–1.7, P<0.0001).2

The outcome of surrogate markers of perfusion was not assessed because adequate evidence was identified to answer the PICO question for the higher priority outcomes.

Treatment recommendation

We suggest that atropine (0.04 mg/kg IV) may be administered once during CPR for dogs and cats with non-shockable arrest rhythms (weak recommendation, low quality of evidence).

We recommend that if atropine is used, it is given as early as possible in the CPR effort (strong recommendation, very low quality of evidence).

We recommend against administering repeated doses of atropine during CPR for dogs and cats with non-shockable arrest rhythms (strong recommendation, very low quality of evidence).

We recommend the use of atropine (0.04 mg/kg IV) in dogs and cats with bradycardia causing hemodynamic compromise to attempt to prevent progression to CPA (strong recommendation, expert opinion).

Justification of treatment recommendation

The evidence surrounding the potential benefit of atropine during CPR for patients with non-shockable arrest rhythms is conflicting and extremely limited. Although the majority of studies showed no difference in outcomes in these patients with administration of atropine, one observational study in humans demonstrated an association between atropine administration and reduced likelihood of survival to discharge2, and one experimental dog study also showed a potential benefit.8 Given the very limited evidence of harm associated with standard dose atropine, the committee suggests that the use of atropine in dogs and cats with non-shockable arrest rhythms may be considered, especially if the arrest was preceded by bradycardia due to high parasympathetic tone.

There is convincing evidence that higher doses of atropine are associated with worse outcomes in dogs compared to placebo control.6 Atropine is partially metabolized by the liver and excreted in the urine, does not reach peak plasma concentrations for 3-4 minutes after administration, and has a long half-life. Therefore, we recommend against giving more than one dose of atropine during CPR because multiple doses are likely to lead to accumulation, effectively equivalent to administering a higher dose. Given that the physiologic rationale for the use of atropine is the potential that high vagal tone may have contributed to the arrest, we recommend that atropine be given as early in the CPR attempt as possible.

Knowledge gaps

The incidence of vagally mediated arrests in dogs and cats is unknown, but is assumed to be relatively high in hospitalized patients. There are no studies evaluating the utility of atropine in dogs and cats with high vagal tone and/or bradycardia at the time of the arrest, The majority of the studies included either experimentally induced arrest in healthy dogs, or OOH arrest, with long response times and generally dismal outcomes.