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

OBS

0

- -

-

-

0

0

0

Two observational studies suggest higher ventilation rates are associated with better neurological outcomes in adult and pediatric human patients. One observational study in adults found no difference with <10bpm vs > 10 bpm

Very low

1

EX

0

-

-

0

0

0

0

In a swine study there was no difference in neurologic outcome when 10 vs 35 breaths per minute were used.

Very low

Outcome: Survival to discharge

2

OBS

0

- -

-

-

0

0

0

One observational study suggested higher ventilation rates were associated with better survival to discharge in pediatric human patients. One observational study in adults found no difference with <10bpm vs > 10 bpm

Very low

1

EX

0

- -

-

0

0

0

0

In a swine study there was no difference in survival to discharge when 10 vs 35 breaths per minute were used

Very low

Outcome: ROSC

2

OBS

0

- -

-

-

0

0

0

One observational study suggested higher ventilation rates were associated with better ROSC in pediatric human patients. One observational study in adults found no difference with <10bpm vs > 10 bpm

Very low

4

EXP

0

-

-

-

0

0

0

3 experimental swine studies comparing ventilation rates of ~10 vs 30bpm found no difference in ROSC. One experiential swine study found higher rates of ROSC with 12bpm compared to 30 bpm

Very low

Outcome: Surrogate markers of perfusion

1

OBS

0

- -

-

0

0

0

0

One observational study suggested no association between ventilation rates and arterial blood pressure

in pediatric human patients.

Very low

8

EX

0

- -

-

-

0

0

0

Two experimental studies favored lower ventilation rates, one dog study with synchronized ventilation favored higher ventilation rates and 5 studies found no difference with ventilation rate.

Very low

Outcome: PaCO2

4

EX

0

- -

-

-

0

0

0

Of these 4 experimental studies, 2 swine studies of ventilation rate of ~10pbm vs 30bpm, found PaCO2 to higher in the lower ventilation rate group. One swine and canine study found no difference in PaCO2 with differing ventilation rates.

Very low

Outcome: Oxygenation

5

EX

0

- -

-

0

0

0

0

Five experimental studies (4 swine, 1 canine) found no difference in oxygenation with variable ventilation rates

Very low

Introduction

Providing rescue breaths during CPR has been shown to improve oxygenation, ventilation, and outcomes, but these benefits must be weighed against the potential negative cardiovascular consequences of positive pressure breaths. Increases in intrathoracic pressure associated with positive pressure breaths can reduce venous return and cardiovascular performance during chest compressions.1 In addition it has long been known that hyperventilation can lead to hypocapnia-associated cerebral vasoconstriction that may worsen neurologic outcomes.2 The current human and previous veterinary CPR guidelines recommend a ventilation rate of 10 breaths per minute.3,4

Consensus on science

Outcome 1: Favorable neurologic outcome

For the most critical outcome of FNO, we found 3 observational studies in people (very low quality of evidence, downgraded for very serious indirectness, serious imprecision, and serious inconsistency) and 1 experimental study in swine (very low quality of evidence, downgraded for very serious indirectness and serious imprecision) that address the PICO question.5–8 In an observational study directly comparing CPR ventilation rates (mean +/- SD) in 285 adult survivors of OHCA with a better cerebral performance category (CPC) of 1-2 to rates in those with worse CPC of 3-5, CPR ventilation rates had been higher (12.7 +/- 6.1 vs 7.3 ± 3.5 breaths per minute (bpm)) in patients that achieved a better CPC. Additionally, in multivariate analysis, increasing ventilation rate was associated with a favorable neurologic outcome (CPC 1-2 vs 3-5) [OR (95%CI) 3.795 (1.507–9.557)].7 Another study in 337 adults with OHCA compared ventilation rates of < 10 bpm to rates > 10 bpm and found no difference between groups in FNO at 1 year.6 In 18 children experiencing IHCA, a ventilation rate of > 30 bpm in < 1-year-olds or > 25 bpm in 1- to 17-year-olds had an OR (95%CI) of 4.73 (1.17 – 19.13) for FNO compared to lower rates.8 An experimental swine study using a fibrillatory arrest model compared FNO at 24 hours in pigs receiving a ventilation rate of 10 bpm at 10 ml/kg to those receiving a rate of 35 bpm at 20 ml/kg; no difference in FNO was found.5

Outcome 2: Survival to discharge

For the critical outcome of survival to discharge, we found 2 observational studies6,8 (very low quality of evidence, downgraded for very serious indirectness, serious imprecision, and serious inconsistency) and 1 experimental animal trial5 (very low quality of evidence, downgraded for very serious indirectness and serious imprecision) that addressed the PICO question. In 47 children experiencing IHCA, a ventilation rate of > 30 bpm in < 1-year-olds or > 25 bpm in 1- to 17-year-olds had an OR (95%CI) of 4.73 (1.32 - 16.27) for improved survival to discharge compared to patients in whom lower RRs were used.8 Another study in 337 adults with OHCA compared ventilation rates of < 10 bpm to rates > 10 bpm and found no difference between groups in likelihood of survival to discharge.6 An experimental swine study using a fibrillatory arrest model compared survival at 24 hours in pigs receiving a ventilation rate of 10 bpm at 10 ml/kg to those receiving a rate of 35 bpm at 20 ml/kg; no difference in 24-hour survival was found.5

Outcome 3: ROSC

For the critical outcome of ROSC we identified 2 observational studies6,8 (very low quality of evidence, downgraded for very serious indirectness, serious imprecision, and serious inconsistency) and 4 experimental studies5,6,9–11 (very low quality of evidence, downgraded for serious indirectness, serious imprecision, and serious inconsistency) that address the PICO question. One study in 337 adults with OHCA compared ventilation rates of < 10 bpm to rates > 10 bpm and found no difference between groups in likelihood of ROSC.6 In 47 children experiencing 52 events of IHCA, a ventilation rate of > 30 bpm in < 1-year-olds or > 25 bpm in 1- to 17-year-olds had an OR (95%CI) of 4.64 (1.17 – 19.13) for increased incidence of ROSC compared to events in which lower RRs were used.8 An experimental swine study using a fibrillatory arrest model compared ROSC in pigs receiving a ventilation rate of 10 bpm at 10 ml/kg to those receiving a rate of 35 bpm at 20 ml/kg; no difference in ROSC was found.5 In a second swine study of fibrillatory CPA, a RR of 10 vs 33 bpm at tidal volumes of both 6 and 18 ml/kg had no statistical association with ROSC.9 An experimental piglet study of asphyxial arrest compared ventilation rates of 10, 20, and 30 bpm and found no difference in ROSC.10 A final experimental swine study compared CPR using 12 bpm or 30 bpm; ROSC was significantly greater (6/7) in pigs receiving 12 bpm compared to those (1/7) receiving 30 bpm.11

Outcome 4: Surrogate markers of perfusion

For the important outcome of surrogate markers of perfusion, we found 1 observational study8 (very low quality of evidence, downgraded for very serious indirectness and serious imprecision) and 8 experimental animal studies5,8–15 (very low quality of evidence, downgraded for very serious indirectness, serious imprecision, and serious inconsistency) that address the PICO question. In 47 children experiencing 52 events of IHCA, ventilation rate was not associated with arterial blood pressure.8 In an experimental swine study, a respiratory rate of 10 vs 33 bpm at tidal volumes of both 6 and 18 ml/kg was not associated with aortic pressure, right atrial pressure, carotid blood flow, CoPP, or CePP. ETCO2 was lower with higher ventilation rates and tidal volumes.9 A fibrillatory swine study found that a RR of 2 bpm resulted in lower brain oxygen tension, carotid blood flow, right atrial systolic pressure, and intracranial systolic pressure, than did a RR of 10 bpm.15 In a fibrillatory canine model comparing a RR of 10 bpm (not synchronized) with a RR of 30 bpm (synchronized), dogs ventilated at 30 bpm (synchronized) had higher right atrial pressure, higher carotid artery pressure, higher jugular vein pressure, and higher carotid artery-RAP gradient (approximation of CePP). Left carotid artery flow was also significantly higher in the 30bpm (synchronized) group.13 An additional 5 experimental swine studies showed no difference in any surrogate marker of perfusion measured with variable ventilation rates.5,10–12,14

Outcome 5: PaCO2

For the important outcome of PaCO2, we found 4 experimental animal studies (very low quality evidence, downgraded for very serious indirectness, serious imprecision, and serious inconsistency) that address the PICO question.5,10,11,13 An experimental swine study of fibrillatory arrest compared ventilation patterns of 10 bpm at 10 ml/kg vs 35 bpm at 20 ml/kg and showed that the 35 bpm group had an inappropriately low PaCO2 while the 10 bpm group had mean PaCO2 in the low 30s.5 An experimental swine study comparing 12 vs 30 bpm showed that the 30 bpm group had a lower PaCO2.11 In an asphyxial arrest model in 1-2-month-old piglets comparing 10 vs 20 vs 30 bpm, no differences in PaCO2 at 3, 8, 18, and 24 minutes of CPR were found.10 In an experimental canine study comparing a RR of 10 bpm (not synchronized) with 30 bpm (synchronized), no difference in PaCO2 at 7 min of CPR was found.13

Outcome 6: Oxygenation

For the important outcome of oxygenation, we found 5 experimental studies (very low quality of evidence, downgraded for very serious indirectness and serious imprecision) that address the PICO question.5,9,10,13,14 All 5 experimental studies (4 swine and 1 canine) found no differences in oxygenation with different ventilation rates used. 5,9,10,13,14

Treatment recommendation

In intubated dogs and cats undergoing CPR, we recommend a respiratory rate of 10 breaths per minute.(very low quality of evidence, expert opinion)

Justification of treatment recommendation

For the outcome of survival to discharge and favorable neurological outcome, there are mixed findings. The studies suggesting a benefit of higher ventilation rates were all of a very low quality for our population. However, for the outcomes of ROSC, surrogate markers of perfusion, and PaCO2, a preponderance of the evidence supports the use of lower ventilation rates. The committee selected a breathing rate of 10 per minute to maintain consistency for the purpose of ETCO2 monitoring and for ease of rescuer performance.

Knowledge gaps

Effect of ventilation rate during CPR in clinical trials in any species is lacking. Drawing conclusions from experimental studies, even the one study performed in dogs, is difficult because of the nature of the arrest and the methods of CPR. Additional studies without the use of an impedance threshold device would be beneficial.