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: Survival to discharge

3

OBS

-

- -

0

0

0

0

0

Very low

Introduction

Opioid medications are commonly used as analgesics in dogs and cats. In a large retrospective study of over 2,000,000 hospitalized human patients, those receiving a combination of opioids and sedatives had an adjusted odds ratio of developing CPA of 3.47 (95% CI: 3.40–3.54; p<0.0001), while those receiving opioids alone had an odds ratio for CPA of 1.81 (95% CI: 1.77–1.85; p<0.0001).1 This PICO question evaluated the utility of administering naloxone to patients who had recently received an opioid prior to CPA.

Consensus on science

Outcome 1: Favorable neurologic outcome

No studies were identified that addressed the outcome of favorable neurologic outcome.

Outcome 2: Survival to discharge

Three observational studies in humans (very low-quality evidence, downgraded for serious risk of bias and serious indirectness) provided some evidence regarding the use of naloxone in patients experiencing CPA potentially related to opioid exposure. In a retrospective registry study of 2342 OOH CPA patients, 180 (7.7%) were suspected to be related to opioid overdose and were administered naloxone.2 Patients suspected of opioid overdose and administered naloxone had a higher rate of survival to hospital discharge (19% vs. 12%, P = 0.014) than non-overdose patients. However, there was no control population suspected of opioid overdose that did not receive naloxone for comparison. In a retrospective observational study of 726 patients with opioid overdose, 609 (85.4%) had pulses on presentation, and 94% of those responded to naloxone administration.3 Naloxone was administered in the 16 patients in CPA in which CPR was attempted. Two developed ROSC, but none survived to discharge. In a third retrospective, observational study of 36 patients with OOH CPA administered naloxone because of suspected pre-arrest opioid use, 15 (42% [95% confidence interval [CI]: 26–58]) showed improvement in the ECG rhythm. The majority presented with PEA or asystole. Three patients achieved ROSC, but only 1 patient survived to discharge.

Outcomes 3 and 4: ROSC and Surrogate markers of perfusion

No additional studies were identified that addressed these outcomes.

Treatment recommendation

In cats and dogs with CPA after recently administered opioid drugs, we recommend that once BLS and other high priority ALS interventions have been initiated, naloxone should be administered (0.04 mg/kg IV). (strong recommendation, very low quality of evidence)

We recommend immediate administration of naloxone (0.04 mg/kg IV) in dogs and cats not in CPA that are bradycardic and/or unresponsive after administration of an opioid. (strong recommendation, very low quality of evidence)

Justification of treatment recommendation

Although there are no clinical trials or experimental studies that directly answer this PICO question, naloxone administration in patients that recently received opioids is a low-risk intervention and is effective at reversing life-threatening opioid overdose in people who are not yet in CPA. In addition, one retrospective observational study in humans showed that patients with OOH CPA associated with opioid overdose administered naloxone have higher survival to discharge rates than patients arresting due to other causes, suggesting that attempting CPR in these patients is worthwhile.1 In dogs and cats that are known or suspected to have received an opioid overdose that may have precipitated the arrest, administration of naloxone may theoretically have even more of a benefit.

For patients that have not arrested but have received an overdose of an opioid or are bradycardic or unresponsive after receiving an opioid, the committee recommends immediate administrative of naloxone to attempt to prevent CPA based on the literature evaluated to answer this PICO question.

Knowledge gaps

No clinical or experimental studies have specifically addressed the question of whether naloxone is beneficial in humans, cats or dogs with CPA in close proximity to opioid administration. In addition, there is no evidence about an optimal or maximum duration between opioid exposure and effective naloxone administration in dogs, cats or humans with CPA.