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ALS-13-v1
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1 RECOVER 2.0 Worksheet
2 QUESTION ID: ALS-13
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PICO Question:
In cats and dogs with CPA after recently administered opioid drugs (P) does not administering naloxone (I) compared to naloxone administration (C) improve outcome (O)?
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Outcomes:
Favorable neurologic outcome, Surrogate marker(s) of perfusion, Survival to discharge, ROSC
5 Prioritized Outcomes (1 = most critical; final number = least important):
- 6 Favorable neurological outcome
- 7 Survival to discharge
- 8 ROSC
- 9 Surrogate markers of perfusion
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Domain chairs: Gareth Buckley, Elizabeth Rozanski; final edit by Dan Fletcher
11 Evidence evaluators: April Blong, Sarah Cudney
12 Conflicts of interest: None
13 Search strategy: See attached document
14 Evidence Review:
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15 Study Design |
16 Reduced Quality Factors
17 0 = no serious, - = serious,
18 - - = very serious |
19 Positive Quality Factors
20 0 = none, + = one, ++ = multiple |
21 Dichotomous Outcome Summary |
22 Non-Dichotomous Outcome Summary
23 Brief description |
24 Overall Quality
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High, moderate, low, |
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26 No of studies |
27 Study Type |
28 RoB |
29 Indirectness |
30 Imprecision |
31 Inconsistency |
32 Large Effect |
33 Dose-Response |
34 Confounder |
35 # Intervention with Outcome |
36 # Control with Outcome |
37 RR (95% CI) |
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38 Outcome: Survival to discharge
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39 3 |
40 OBS |
41 - |
42 - - |
43 0 |
44 0 |
45 0 |
46 0 |
47 0 |
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48 Very low |
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49 PICO Question Summary
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50 Introduction |
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51 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. |
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52 Consensus on science |
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53 Outcome 1: Favorable neurologic outcome
54 No studies were identified that addressed the outcome of favorable neurologic outcome.
55 Outcome 2: Survival to discharge
56 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.
57 Outcomes 3 and 4: ROSC and Surrogate markers of perfusion
58 No additional studies were identified that addressed these outcomes.
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59 Treatment recommendation |
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60 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)
61 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)
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62 Justification of treatment recommendation |
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63 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.
64 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. |
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65 Knowledge gaps |
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66 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. |
67 References:
68 1. Overdyk FJ, Dowling O, Marino J, et al. Association of Opioids and Sedatives with Increased Risk of In-Hospital Cardiopulmonary Arrest from an Administrative Database. Lazzeri C, ed. PLOS ONE. 2016;11(2):e0150214.
69 2. Koller AC, Salcido DD, Callaway CW, Menegazzi JJ. Resuscitation characteristics and outcomes in suspected drug overdose-related out-of-hospital cardiac arrest. Resuscitation. 2014;85(10):1375-1379.
70 3. Sporer KA, Firestone J, Isaacs SM. Out-of-hospital treatment of opioid overdoses in an urban setting. Acad Emerg Med. 1996;3(7):660-667.
71 Supplemental:
72 S2D:
73 Saybolt, 2010: Retrospective observational registry study of 36 patients OOH administered naloxone because of suspicion of pre-arrest opiod use.
74 Fifteen of the 36 (42%) (95% confidence interval [CI]: 26–58) patients in cardiac arrest who received naloxone in the pre-hospital setting had an improvement in electrocardiogram (EKG) rhythm and 21 did not have an improvement. The majority had PEA or asystole. 3 patients achieved ROSC, and only 1 patient survived to discharge
75 Sporer, 1996: Retrospective observational study of 726 patients with opioid overdoses. 609 (85.4%) had pulses on presentation and 94% responded to naloxone administration. 16 patients with CPA that had CPR with naloxone administration. Two developed ROSC, but neither survived to discharge.
76 Koller 2014: Retrospective registry study of 2342 OOH arrests. 180 (7.7%) were suspected overdose cases and were administered naloxone. Overdose cases had had a higher rate of survival to hospital discharge (19% vs. 12%, p =0.014) than non-overdoses.
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