ALS-10-v1

1 RECOVER 2.0 Worksheet

2 QUESTION ID: ALS-10

3 PICO Question:
In euvolemic cats and dogs with CPA (P) does the use of an intravenous fluid bolus (I) compared to not using an intravenous fluid bolus (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 1. Favorable neurological outcome

7 2. Survival to discharge

8 3. ROSC

9 4. Surrogate markers of perfusion

10 Domain chairs: Gareth Buckley, Elizabeth Rozanski (Fletcher)

11 Evidence evaluators: Melissa Claus, Tatiana Henriques Ferreira

12 Conflicts of interest: None reported

13 Search strategy: See attached document

14 Evidence Review:

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, very low, none
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)
38 Outcome: Favorable neurologic outcome
39 0
40 Outcome: Survival to discharge
41 0
42 Outcome: ROSC
43 1	44 Ex	45 -	46 - -	47 0	48 0	49 0	50 0	51 0					52 Very low
53 Outcome: Surrogate markers of perfusion
54 5	55 Ex	56 -	57 - -	58 0	59 0	60 0	61 0	62 0					63 Very low

64 PICO Question Summary

65 Introduction

66 Fluid boluses have historically been administered during CPR with the goal of increasing cardiac filling in order to increase cardiac output (CO). However, during CPR in euvolemic patients that do not have cardiac filling deficits, coronary perfusion pressure (CoPP) and cerebral perfusion pressure (CePP) may be decreased by fluid boluses in that they may increase central venous and right atrial pressure more than aortic systolic and diastolic pressure. The RECOVER 2012 Guidelines recommended against routine administration of IV fluid boluses during CPR unless patients had known or strongly suspected hypovolemia 1. This was based on the concept that in hypovolemic patients in CPA, fluid boluses will likely increase ventricular filling, leading to increases in aortic systolic and diastolic pressure that exceed increases in central venous and right atrial pressures, improving CoPP and CePP. This PICO question examines the effect on outcome of fluid boluses during CPR in euvolemic patients.

67 Consensus on science

68 Outcomes 1, 2: Favorable neurologic outcome, survival to discharge

69 For the 2 most critical outcomes of favorable neurologic outcome and survival to discharge, no evidence was available to inform an answer to the PICO question.

70 Outcome 3: Return of spontaneous circulation

71 There is 1 experimental study that provides some indirect evidence of a beneficial effect of volume loading in euvolemic dogs undergoing CPR (very low quality of evidence, downgraded for serious risk of bias and very serious indirectness). Sanders et al examined

72 31 mongrel dogs with prolonged induced ventricular fibrillation in which CPR was done for 30 minutes prior to the first shock.2 Dogs receiving fluid boluses and sodium bicarbonate prior to arrest and during the CPR attempt had higher ROSC rates than those that did not receive fluids or sodium bicarbonate (8/11 vs. 0/10). Two additional groups were evaluated with a similar protocol, but 1 group received only fluids and the other only bicarbonate. Incidence of ROSC was similar between these groups (2/12 vs. 5/14), but ROSC incidence was significantly higher in the group of dogs receiving both bicarbonate and fluids.

73 Outcome 4: Surrogate markers of perfusion

74 For the outcome of surrogate markers of perfusion, 4 experimental studies in dogs and 1 experimental study in cats (very low quality of evidence, downgraded for serious risk of bias and very serious indirectness due to confounding interventions) overall showed no improvement or a detrimental effect of fluid boluses on CoPP and/or CePP.2–6 Although the studies generally demonstrated a consistent increase in aortic pressure and blood flow, the concurrent increase in CVP in the animals either yielded no net improvement or a decrease in CoPP and/or CePP.

75 Gentile et al. compared aortic systolic (SAoP) and diastolic pressures (DAoP), right atrial systolic (SRAP) and diastolic pressures (DRAP), and coronary perfusion pressure (CoPP) in 19 healthy anesthetized dogs undergoing CPR for induced ventricular fibrillation (VF) that either received epinephrine and defibrillation alone (n=6), epinephrine plus a 500 mL bolus (16-23 mL/kg) of 0.9% saline intravenously (n=5), or epinephrine plus a 500ml bolus of 0.9% saline into the aorta (n=8).6 SAoP, DAoP, SRAP and DRAP all increased significantly with fluid boluses, but maximal CoPP did not significantly differ between groups. Ditchey and Lenfield studied 12 dogs using a model of induced VF.4 Measurements of carotid blood flow showed increases with fluid boluses (1L of 0.9% NaCl or 10% HES) but cerebral and coronary blood flow decreased with fluid boluses, presumably due to increased venous pressure. In a study of 31 mongrel dogs, Sanders et al. showed no differences in CoPP in a prolonged VF model (CPR was performed for 30 minutes before the first shock) between dogs receiving an infusion of fluids pre-arrest to achieve a right atrial pressure of 6-8 mmHg and infusions of sodium bicarbonate during the arrest and dogs not receiving fluids or sodium bicarbonate.2 Finally, Fischer and Hossman studied 14 cats using an induced VF model.3 All cats had standard CPR with chest compressions, epinephrine and electrical defibrillation. Six cats were additionally volume loaded with 2ml/kg HES over 10 minutes. Cats that received HES had significantly less evidence of cerebral ischemia on necropsy, though they had decreased CoPP and CePP during CPR. All cats achieved ROSC.3

76 Treatment recommendation

77 We recommend against the use of intravenous fluid boluses in euvolemic dogs and cats during CPR (strong recommendation, very low quality of evidence).

78 We recommend the use of intravenous fluid boluses in dogs (20 ml/kg isotonic crystalloid or equivalent) and cats (10-15 ml.kg isotonic crystalloid or equivalent) with known or suspected hypovolemia during CPR (strong recommendation, expert opinion).

79 Justification of treatment recommendation

80 All evidence available to inform this treatment recommendation is experimental, is in ventricular fibrillation models, and much of it is confounded by multiple concurrent treatments including sodium bicarbonate administration. However, there is consistent evidence that fluid boluses administered during CPR to dogs and cats that are euvolemic prior to induced CPA lead to increases in right atrial pressure that exceed increases in aortic pressure, leading to decreased CoPP and CePP, suggesting that fluid boluses are in general detrimental in this population. One study showed significant increases in the incidence of ROSC in dogs treated prior to induction of VF with fluid boluses and sodium bicarbonate compared to dogs receiving either fluid boluses alone, sodium bicarbonate alone, or neither.2 This is confounded by the fact that this treatment started prior to induction of VF and by the fact that these were anesthetized, experimental dogs that underwent prolonged CPR for 30 minutes prior to the first attempt at electrical defibrillation.

81 Knowledge gaps

82 Although there is compelling experimental evidence suggesting that fluid boluses decrease CoPP and CePP in induced ventricular fibrillation models of CPA, there are no clinical trials evaluating the effects of fluid boluses in clinical patients during CPR. However, given the experimental evidence, it is difficult to suggest that there is adequate clinical equipoise to warrant a clinical trial.

83 References:

84 1. Fletcher DJ, Boller M, Brainard BM, et al. RECOVER evidence and knowledge gap analysis on veterinary CPR. Part 7: Clinical guidelines: RECOVER clinical guidelines. J Vet Emerg Crit Care. 2012;22(s1):S102-S131.

85 2. Sanders AB, Kern KB, Fonken S, Otto CW, Ewy GA. The role of bicarbonate and fluid loading in improving resuscitation from prolonged cardiac arrest with rapid manual chest compression CPR. Ann Emerg Med. 1990;19(1):1-7.

86 3. Fischer M, Hossmann KA. Volume expansion during cardiopulmonary resuscitation reduces cerebral no-reflow. Resuscitation. 1996;32(3):227-240.

87 4. Ditchey RV, Lindenfeld J. Potential adverse effects of volume loading on perfusion of vital organs during closed-chest resuscitation. Circulation. 1984;69(1):181-189.

88 5. Voorhees Iii WD, Ralston SH, Kougias C, Schmitz PMW. Fluid loading with whole blood or ringer’s lactate solution during cpr in dogs. Resuscitation. 1987;15(2):113-123.

89 6. Gentile NT, Martin GB, Appleton TJ, Moeggenberg J, Paradis NA, Nowak RM. Effects of arterial and venous volume infusion on coronary perfusion pressures during canine CPR. Resuscitation. 1991;22(1):55-63.

90 Supplemental:

91 Fischer and Hossman (Resuscitation, 1996) [1419]

92 14 cats, induced VF, 8 cats standard resuscitation with epi and shocks, 6 cats also got 2ml/kg HES over 10 minutes. Cats in the exp group had significantly reduced cerebral no-flow volume (28 vs 15% of forebrain volume) in the PCA period but decreased myocardial and cerebral perfusion pressure during CPR. All cats achieved ROSC.

93 Sanders et al, 1990, Annals of Emerg Med [1414]

94 31 mongrel dogs, Group A comps 120/min + bicarb and fluids (24-hour survival in 7/11), Group B no bicarb or fluids (0/10) , Group C 80/min with bicarb and fluids (3/10). Fluids were loaded pre-arrest to achieve RAP of 6-8 mmHg. No differences in CoPP between groups A and B. Two additional groups (comps at 120 with fluids vs comps at 120 with bicarb) were not different from each other but had lower survival than group A.

95 Ditchey and Lenfield, Circulation, 1984 [1421]

96 12 mongrel dogs, induced VF, closed chest compressions. Measurements of carotid blood flow showed increases with fluid boluses (1L of 0.9% NaCl or 10% HES) but cerebral and coronary blood flow decreased with fluid boluses, presumably due to increased venous pressure.

97 Vorhees et al, Resuscitation, 1987 [1413]

98 18 mongrel dogs, induced VF, after 10 minutes received rapid infusion of 11 ml/kg of either blood or LRS. CO increased by 34%, but left ventricular perfusion decreased by 74% and cerebral blood flow decreased by 65%. CVP increased significantly with fluid bolus (9 -> 14 mmHg) but aortic diastolic pressure did not (32 -> 34 mmHg).

99 Gentile et al., Resuscitation, 1991 [1418]

100 19 mongrel dogs, 6 received epi alone, 5 received epi plus a fluid bolus (500ml saline) IV, 8 received epi plus the bolus into the aorta. Ao systolic, Ao diastolic, and RA pressures all increased significantly with the fluid bolus, but CoPP were the same between groups.

DMU Timestamp: July 13, 2023 21:18