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ALS-08-v1
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1 RECOVER 2.0 Worksheet
2 QUESTION ID: ALS-08
3
PICO Question:
In cats and dogs with CPA (P) does the use of high dose epinephrine (0.1mg/kg IV) (I) compared to standard dose epinephrine (0.01mg/kg IV) (C) improve outcome (O)
4
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 neurologic outcome
- 7 Survival to discharge
- 8 ROSC
- 9 Surrogate markers of perfusion
10
Domain chairs: Gareth Buckley, Elizabeth Rozanski (this evidence summary completed by Jamie Burkitt)
11 Evidence evaluators: Lindsey Strang, Erik Zager
12 Conflicts of interest: None reported
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
25
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: Favorable neurologic outcome |
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39 4 |
40 CT |
41 0 |
42 - - |
43 0 |
44 0 |
45 0 |
46 0 |
47 0 |
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48 Low |
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49 2 |
50 EXPT |
51 0 |
52 - - |
53 0 |
54 0 |
55 0 |
56 0 |
57 0 |
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58 Very low |
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59 Outcome: Survival to Discharge |
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60 6 |
61 CT |
62 0 |
63 - - |
64 0 |
65 0 |
66 0 |
67 0 |
68 0 |
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69 Low quality |
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70 3 |
71 EXPT |
72 0 |
73 - - |
74 0 |
75 0 |
76 0 |
77 0 |
78 0 |
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79 Very low quality |
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80 Outcome: ROSC |
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81 6 |
82 CT |
83 0 |
84 - - |
85 0 |
86 - |
87 0 |
88 0 |
89 0 |
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90 Very low |
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91 6 |
92 EXPT |
93 0 |
94 - |
95 0 |
96 0 |
97 0 |
98 0 |
99 0 |
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100 Low |
101 PICO Question Summary
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102 Introduction |
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103 Limited evidence is available to determine the ideal dose of epinephrine during CPR in dogs and cats. Experimental and limited clinical evidence have suggested that high-dose epinephrine (~ 0.1 mg/kg) may improve chances of ROSC but may worsen survival or neurologic outcome when compared to low- (standard-) dose epinephrine (~ 0.01 mg/kg).1 Examination of literature surrounding this PICO question aimed to determine whether there is a benefit to routine use of high-dose epinephrine (as opposed to low-dose) in CPR in dogs and cats.
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104 Consensus on science |
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105 Outcome 1: Favorable neurologic outcome
106 For the most critical outcome of favorable neurologic outcome, we identified 4 clinical trials (low quality of evidence, downgraded for very serious indirectness) and 2 experimental studies (very low quality of evidence, downgraded for very serious indirectness) that addressed the PICO.2–7 All 4 clinical trials investigated OHCA in human adults; the largest included 3327 people and all 4 combined contained ~5500 subjects. None of the 4 trials showed improvement in neurologic outcome at discharge when comparing high-dose epinephrine to standard, low-dose epinephrine. One trial containing only 816 people suggested a trend toward worse FNO with high-dose epinephrine.2 Both experimental studies that addressed FNO were in swine, and neither found a difference in FNO at 24 hours when comparing high-dose to standard-dose epinephrine; both studies used 0.2 mg/kg as “high dose” and 0.02 mg/kg as “low dose.”
107 Outcome 2: Survival to discharge
108 For the next most critical outcome of survival to discharge, we identified 6 clinical trials (low quality of evidence, downgraded for very serious indirectness) and 3 experimental studies (very low quality of evidence, downgraded for very serious indirectness) that addressed the PICO question.2–10 The 2 clinical trials here that were not listed under FNO were small, and together contributed only ~600 additional people, 68 of which were pediatrics with IHCA. Five of 6 trials found no benefit to high-dose epinephrine compared to low-dose epinephrine on survival to discharge. One trial in children with IHCA showed worse neurologic status at 24 hours post-CPR with high-dose compared to low-dose epinephrine, and no children in the high-dose group survived to discharge compared to 4 children in the low-dose epinephrine group.8 Three experimental studies, 2 in swine and 1 in dogs found no improvement in 24-hour survival (swine) or 2-hour survival (dogs) when high-dose was compared to low-dose epinephrine.6,7,10
109 Outcome 3: ROSC
110 We identified 6 clinical trials (very low quality of evidence, downgraded for very serious indirectness and serious inconsistency) and 6 experimental studies (low quality of evidence, downgraded for serious indirectness) that addressed the next critical outcome of ROSC.2–13 Two of the clinical trials, one of which was the largest trial including 3327 adults with OHCA found that high-dose epinephrine improved ROSC compared to low-dose epinephrine, while the other 4 trials failed to find a difference.2,5 Of the 6 experimental trials, none found an improvement in ROSC with use of high-dose compared to low-dose epinephrine; 3 studies were performed in dogs and one in cats. Despite this, 2 of the canine studies found that ROSC was achieved more quickly with high-dose epinephrine than with low-dose epinephrine.10,13 |
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111 Treatment recommendation |
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112 We recommend against the routine use of high-dose epinephrine during CPR in dogs and cats (strong recommendation, low quality of evidence).
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113 Justification of treatment recommendation |
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114 There is no evidence for the routine use of high-dose epinephrine to improve neurologic outcome or survival in dogs, cats, or other species, and some limited information in people suggests worse neurologic outcome and short-term (24h) survival with high doses. There is inconsistent evidence for improvement in ROSC with use of high-dose epinephrine in people, and no evidence for improvement in ROSC in experimental models in dogs, cats, or swine.
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115 Knowledge gaps |
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116 There are no observational studies or clinical trials in the target species to investigate the possible utility of high-dose epinephrine in dogs and cats.
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117 References:
118 1. Vandycke C, Martens P. High dose versus standard dose epinephrine in cardiac arrest - a meta-analysis. Resuscitation. 2000;45(3):161-166.
119 2. Callaham M, Madsen CD, Barton CW, Saunders CE, Pointer J. A randomized clinical trial of high-dose epinephrine and norepinephrine vs standard-dose epinephrine in prehospital cardiac arrest. JAMA. 1992;268(19):2667-2672.
120 3. Brown CG, Martin DR, Pepe PE, et al. A comparison of standard-dose and high-dose epinephrine in cardiac arrest outside the hospital. The Multicenter High-Dose Epinephrine Study Group. N Engl J Med. 1992;327(15):1051-1055.
121 4. Stiell IG, Hebert PC, Weitzman BN, et al. High-Dose Epinephrine in Adult Cardiac Arrest. New England Journal of Medicine. 1992;327(15):1045-1050.
122 5. Gueugniaud PY, Mols P, Goldstein P, et al. A comparison of repeated high doses and repeated standard doses of epinephrine for cardiac arrest outside the hospital. European Epinephrine Study Group. N Engl J Med. 1998;339(22):1595-1601.
123 6. Berg RA, Otto CW, Kern KB, et al. A randomized, blinded trial of high-dose epinephrine versus standard-dose epinephrine in a swine model of pediatric asphyxial cardiac arrest. Crit Care Med. 1996;24(10):1695-1700.
124 7. Berg RA, Otto CW, Kern KB, et al. High-dose epinephrine results in greater early mortality after resuscitation from prolonged cardiac arrest in pigs: a prospective, randomized study. Crit Care Med. 1994;22(2):282-290.
125 8. Perondi MBM, Reis AG, Paiva EF, Nadkarni VM, Berg RA. A comparison of high-dose and standard-dose epinephrine in children with cardiac arrest. N Engl J Med. 2004;350(17):1722-1730.
126 9. Choux C, Gueugniaud PY, Barbieux A, et al. Standard doses versus repeated high doses of epinephrine in cardiac arrest outside the hospital. Resuscitation. 1995;29(1):3-9.
127 10. Angelos MG, DeBehnke DJ. Epinephrine and high-flow reperfusion after cardiac arrest in a canine model. Ann Emerg Med. 1995;26(2):208-215.
128 11. Roberts D, Landolfo K, Dobson K, Light RB. The effects of methoxamine and epinephrine on survival and regional distribution of cardiac output in dogs with prolonged ventricular fibrillation. Chest. 1990;98(4):999-1005.
129 12. Schmitz B, Fischer M, Bockhorst K, Hoehn-Berlage M, Hossmann KA. Resuscitation from cardiac arrest in cats: influence of epinephrine dosage on brain recovery. Resuscitation. 1995;30(3):251-262.
130 13. Brunette DD, Jameson SJ. Comparison of standard versus high-dose epinephrine in the resuscitation of cardiac arrest in dogs. Ann Emerg Med. 1990;19(1):8-11.
131 Supplemental:
132 803: Berg RA, Otto CW, Kern KB, et al. A randomized, blinded trial of high-dose epinephrine versus standard-dose epinephrine in a swine model of pediatric asphyxia cardiac arrest. Crit Care Med 1996;24:1695-1700.
133 805: Perondi MBM, Reis AG, Paiva EF, et al. A comparison of high-dose and standard-dose epinephrine in children with cardiac arrest. N Engl J Med 2004;350:1722-1730.
134 1003: Callaham M, Madsen CD, Barton CW, et al. A randomized clinical trial of high-dose epinephrine and norepinephrine vs standard-dose epinephrine in prehospital cardiac arrest. JAMA 1992;268(19):2667-2672.
135 1004: Brown CG, Martin DR, Pepe PE, et al. A comparison of standard-dose and high-dose epinephrine in cardiac arrest outside the hospital. N Engl J Med 1992;327:1051-1055.
136 1005: Choux C, Gueugniaud P, Barbieux A, et al. Standard doses versus repeated high doses of epinephrine in cardiac arrest outside the hospital. Resuscitation 1995;29:3-9.
137 1006: Stiell IG, Hebert PC, Weitzman BN, et al. High-dose epinephrine in adult cardiac arrest. N Engl J Med 1992;327:1045-1050.
138 1007: Gueugniaud P, Mols P, Goldstein P, et al. A comparison of repeated high doses and repeated standard doses of epinephrine for cardiac arrest outside the hospital. N Engl J Med 1998;339:1595-1601.
139 1016: Roberts D, Landolfo K, Dobson K, Light RB. The effects of methoxamine and epinephrine on survival and regional distribution of cardiac output in dogs with prolonged ventricular fibrillation. Chest 1990;98:999-1005.
140 1018: Schmitz B, Fischer M, Bockhorst K, et al. Resuscitation from cardiac arrest in cats: influence of epinephrine dosage on brain recovery. Resuscitation 1995;30:251-262.
141 1020: Brunette DD, Jameson SJ. Comparison of standard versus high-dose epinephrine in the resuscitation of cardiac arrest in dogs. Ann Emerg Med 1990;19:8-11.
142 1021: DeBehnke DJ, Angelos MG, Leasure JE. Use of cardiopulmonary bypass, high-dose epinephrine, and standard-dose epinephrine in resuscitation from post-countershock electromechanical dissociation. Ann Emerg Med 1992;21:1051-1057.
143 1022: Berg RA, Otto DW, Kern KB, et al. High-dose epinephrine results in greater early mortality after resuscitation from prolonged cardiac arrest in pegis: A prospective, randomized study. Crit Care Med 1994;22:282-290.
144 1023: Angelos MG, DeBehnke DJ. Epinephrine and high-flow reperfusion after cardiac arrest in a canine model. Ann Emerg Med 1995;26:208-215.
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145 PaperID |
146 Citation |
147 N |
148 Pop’n |
149 Scene |
150 HDE /
151 LDE |
152 HDE:
153 Impv FNO |
154 HDE:
155 Impv Surv-timept |
156 HDE:
157 Impv ROSC |
158 Comments |
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159 CT |
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160 805 |
161 Perondi 2004 |
162 68 |
163 P |
164 IHCA |
165 0.1mg/kg /
166 0.01 mg/kg |
167 N/A |
168 WORSE – 24h (UTE d/c) |
169 NO |
170 Sixty-eight kids; HDE worse survival 24h (& d/c) |
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171 1003 |
172 Callaham 1992 |
173 816 |
174 A |
175 OHCA |
176 15 / 1 |
177 NO (“trend” toward
178 worse outcome) |
179 NO |
180 YES |
181 P = 0.1 for worse FNO w HDE |
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182 1004 |
183 Brown 1992 |
184 1280 |
185 A |
186 OHCA |
187 .2mg/kg /
188 .02mg/kg |
189 NO |
190 NO |
191 NO |
192 HDE showed some benefit specifically in PEA |
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193 1005 |
194 Choux 1995 |
195 536 |
196 A |
197 OHCA |
198 5 / 1 |
199 N/A |
200 NO |
201 NO |
202 Neuro was evaluated but unclear that stats were done – not used for FNO |
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203 1006 |
204 Stiell 1992 |
205 650 |
206 A (16+) |
207 About half/half OHCA / IHCA |
208 7 / 1 |
209 NO - Discharge |
210 NO - Discharge |
211 NO |
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212 1007 |
213 Gueugniaud 1998 |
214 3327 |
215 A |
216 OHCA |
217 5 / 1 |
218 NO - Discharge |
219 NO - Discharge |
220 YES |
221 HDE helped ROSC in asystole but not V-Fib |
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222 Expt |
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223 803 |
224 Berg 1996 |
225 30 |
226 Piglets |
227 Expt |
228 0.2mg/kg /
229 0.02mg/kg |
230 NO |
231 NO – 24 hour |
232 NO |
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233 1016 |
234 Roberts 1990 |
235 24 |
236 Canine |
237 Expt |
238 .2 mg/kg /
239 .02 mg/kg |
240 N/A |
241 N/A |
242 NO |
243 Tangential … ? No defib for 25min CC-CPR till then. |
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244 1018 |
245 Schmitz 1995 |
246 14 |
247 Feline |
248 Expt |
249 .2mg/kg /
250 .02mg/kg |
251 N/A* |
252 N/A |
253 NO |
254 *MRI at 3 hours: no diff HDE / SDE. Time to ROSC same. |
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255 1020 |
256 Brunette 1990 |
257 25 |
258 Canine |
259 Expt |
260 0.014mg/kg / .071mg/kg |
261 N/A |
262 N/A |
263 NO |
264 ROSC faster w HDE than SDE. |
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265 1022 |
266 Berg 1994 |
267 30 |
268 Swine |
269 Expt |
270 0.2mg/kg /
271 0.02mg/kg |
272 NO – 24 hour |
273 NO – 24 hour |
274 NO |
275 HDE had worse survival in “ICU period” than SDE |
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276 1023 |
277 Angelos 1995 |
278 30 |
279 Canine |
280 Expt |
281 0.2mg/kg /
282 0.02mg/kg |
283 N/A |
284 NO – two hour |
285 NO |
286 More rapid ROSC w HDE, but no apparent comparison ROSC (Y vs N) between HDE & SDE |
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