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 1: Favorable neurologic outcome

6

OB

0

- -

0

-

0

0

0

Very low

1

EXP

0

- -

-

0

0

0

0

Very low

Outcome 2: Survival to discharge

9

OB

0

--

-

-

0

0

0

Very low

Outcome 3: Prediction of recurrent CPA

0

Outcome: Duration of post-arrest hospitalization

0

Introduction

Acute kidney injury (AKI) is common in patients experiencing ROSC as a consequence of prolonged hypoxemia and hypoperfusion, as well as ischemia-reperfusion injury.1 In both survivors of CPA and many critically ill populations, AKI is considered an adverse outcome that can ultimately affect duration of hospitalization, survival to discharge and long-term prognosis, independent of underlying cause. This PICO question addressed the utility of post-arrest creatinine measurement to improve outcome after ROSC.

Consensus on science

Outcome 1: Favorable neurologic outcome

For the most critical outcome of favorable neurologic outcome, 6 observational studies in people (very low quality of evidence, downgraded for very serious indirectness and inconsistency) and 1 experimental study in dogs (very low quality of evidence, downgraded for very serious indirectness and imprecision) were identified that were relevant to the PICO question.1–6 Four of the 5 observational studies in people showed a lower frequency of FNO in patients developing AKI in the PCA period. One prospective observational study showed that post-arrest patients with less favorable neurologic outcomes had significantly higher rates of AKI than those with FNO (64% vs. 38%, P=0.004).2 Another observational study of adult people in the PCA period showed an odds ratio for poor neurologic outcome of 3.81 (95% CI 1.98-7.33, P = 0.0001) for patients with static or increasing plasma creatinine concentrations 24 hours post-ROSC compared to those whose creatinine decreased during the first 24 hours.3 Yonemoto et al. used admission creatinine to estimate GFR in a prospective observational study of 5112 people and showed that odds ratios for FNO decreased as GFR decreased.6 Isenschmid at al. did a multivariate analysis of admission creatinine (in umol/L) and demographic data including co-morbidities and found an adjusted odds ratio for poor neurologic outcome of 44.33 (95% confidence interval 6.99 to 281.36, P < 0.001).4 In 282 children with ROSC, severe AKI was associated with worse neurologic function following arrest in a study evaluating the utility of therapeutic hypothermia in the PCA period.7 The only observational study in people that did not show an association between AKI and FNO was a retrospective study of 199 people that showed no difference in neurologic outcomes at 3 months post-ROSC between patients with evidence of AKI (85/199, 43%) and those without evidence of AKI.1 The single experimental study in dogs investigated gender-specific differences in 24-hour outcome following ROSC after 9 minutes of untreated cardiac arrest followed by CPR.5 Neurologic outcome was not significantly different between male and female dogs; however, creatinine concentrations progressively increased at 6, 12, and 24 hours post-arrest in female dogs.

Outcome 2: Survival to discharge

For the next most critical outcome of survival to discharge, 9 observational studies in people were identified that addressed the PICO question (very low quality of evidence, downgraded due to very serious indirectness, serious imprecision, and inconsistency).6–14

In a clinical trial evaluating the utility of therapeutic hypothermia in children experiencing ROSC after CPA, 64% of the children developed AKI, of which 41% developed more severe AKI and 3.5% required renal replacement therapy.7 Severe AKI was associated with lower survival at 28 days and at 12 months post-ROSC. There were several more studies that supported these findings in adult humans experiencing ROSC after arrest events, with the majority of patients developing AKI after arrest experiencing higher in-hospital mortality and lower survival rates over time after discharge.1,6,9–13 Incidence of AKI after cardiac arrest was over 40% in one retrospective analysis, and this patient population mirrored common findings in other reports, with AKI patients exhibiting severe hemodynamic impairment and requiring more intensive interventions post-arrest.1 Another study showed that creatinine concentrations at admission following out-of-hospital cardiac arrest were higher in patients that ultimately developed AKI and 30-day mortality was higher in patients with more advanced (stage 3) AKI compared to those with less severe kidney injury.13 There is some evidence in adults that development of AKI (based on the RIFLE scoring system) was not independently associated with survival to discharge; however, renal injury is common, with more than one-third of patients resuscitated from out-of-hospital cardiac arrest events developing markers of renal dysfunction and 19% of those patients meeting the criteria for AKI.14 Both initial creatinine concentrations or low urine output were predictive of development of AKI and peak creatinine concentrations were identified typically during the first 72 hours after arrest. One of the primary findings in that particular study was that the only predisposing factor for development of AKI post-cardiac arrest was the duration of shock after ROSC. Median duration of shock within the first 24 hours post-ROSC was 10 minutes (range 2-59 min) in the non-AKI group compared to 130 minutes (range 48-250 min) in patients that developed AKI. Time from arrest to ROSC, duration of CPR, and serum lactate immediately after ROSC were not associated with development of AKI in that study. Studies are lacking to answer these same questions for dogs or cats experiencing CPA.

Outcomes 3 and 4: Prediction of recurrent CPA and Duration of post-arrest hospitalization

No studies were identified that directly addressed these outcomes for this PICO question.

None of the studies reviewed compared measurement of creatinine to non-measurement with regard to any of the outcomes investigated for this PICO question. There was no evidence in human or veterinary studies available that answer the PICO question with regard to prediction of recurrent CPA events.

Treatment recommendation

We recommend measuring serum creatinine concentrations, as an indicator of AKI, as soon as feasible in the PCA period, and subsequently no less often than every 24 hours during hospitalization in dogs and cats that achieve ROSC. (strong recommendation, very low quality of evidence)

Justification of treatment recommendation

There is consensus in human medicine that post-arrest AKI is associated with worse outcomes, including increased risk of death and decreased frequency of FNO. Therefore, identification of AKI in dogs and cats in the PCA period, especially if the evidence of kidney injury is progressive, may have prognostic value. Despite the frequent measurement of renal values in clinical practice, there is a paucity of literature on creatinine measurement and AKI in dogs and cats experiencing ROSC after CPA. Two experimental studies were reviewed, one in pigs and one in dogs, which provided support for measurement of creatinine in animals after CPR and ROSC.15,16 In an experimental pig model of cardiac arrest, serum creatinine was higher for subjects that experienced CPA when compared to the control group of pigs who did not experience CPA.15 Similarly, in a canine model of cardiac arrest, creatinine concentrations were significantly higher both during CPR and after ROSC, with creatinine increasing approximately 11% and 29% from baseline, respectively.16 Neither study addressed the outcomes evaluated by this particular question and there was no comparison of measurement versus no measurement in study participants.

There have been no studies of the utility of management of AKI guided by serial creatinine measurements to improve outcomes in the PCA period, but monitoring for evidence of development and/or progression of AKI in the PCA period and adjusting management strategies to address kidney injury is likely to be of benefit to these patients.

Knowledge gaps

Currently there is no evidence in dogs and cats that serum creatinine increases in dogs and cats in the PCA period or that increased serum creatinine during CPR or after ROSC are associated with survival to discharge or poor neurologic outcomes. Studies to identify patient factors associated with increased risk of AKI in dogs and cats following ROSC, optimal frequency of creatinine measurement, and to determine whether severity and duration of post-arrest kidney injury has an effect on outcome of these patients are warranted.