Prognostic value of serum phosphate level in adult patients resuscitated from cardiac arrest

doi:10.1016/j.resuscitation.2018.04.026

Resuscitation

Volume 128, July 2018, Pages 56-62

https://doi.org/10.1016/j.resuscitation.2018.04.026 Get rights and content

Abstract

Background

Several studies have reported increased levels of phosphate after cardiac arrest. Given the relationship between phosphate level and the severity of ischaemic injury reported in previous studies, higher phosphate levels may be associated with worse outcomes. We investigated the prognostic value of phosphate level after the restoration of spontaneous circulation (ROSC) in adult cardiac arrest patients.

Methods

This study was a retrospective observational study including adult cardiac arrest survivors treated at the Chonnam National University Hospital between January 2014 and June 2017. From medical records, data regarding clinical characteristics, outcome at hospital discharge, and laboratory parameters including phosphate levels after ROSC were collected. The primary outcome was poor outcome at hospital discharge, defined as Cerebral Performance Categories 3–5.

Results

Of the 674 included patients, 465 had poor outcome at hospital discharge. Serum phosphate level was significantly higher in patients with poor outcome than in those with good outcome (p < 0.001). Phosphate level was correlated with time to ROSC (r = 0.350, p < 0.001). Receiver operating characteristic curve analysis revealed an area under the curve of 0.805 (95% confidence interval [CI], 0.777–0.838) for phosphate level. In multivariate analysis, a higher phosphate level was independently associated with poor outcome at hospital discharge (odds ratio, 1.432; 95% CI, 1.245–1.626; p < 0.001).

Conclusions

A higher phosphate level after ROSC was independently associated with poor outcome at hospital discharge in adult cardiac arrest patients. However, given its modest prognostic performance, phosphate level should be used in combination with other prognostic indicators.

Introduction

Cardiac arrest is a life-threatening emergency, with an incidence of about 1 per 1000 person year [1]. Despite advances in cardiopulmonary resuscitation (CPR) and post-resuscitation care, outcomes after cardiac arrest remain poor [2]. Accurate outcome prediction, particularly early in the treatment process, would help in planning monitoring and treatment strategies. Several modalities including brain-specific biomarkers and neurophysiologic tests have been shown to accurately predict outcomes of cardiac arrest [3], [4], [5], but the results of these tests are not available during the early hours after restoration of spontaneous circulation (ROSC). During this early post-resuscitation phase, physicians frequently rely on arrest and CPR characteristics, such as initial rhythm and bystander CPR status, in order to estimate injury severity and thus predict patient outcome. Although these parameters are well-known predictors of cardiac arrest outcomes [6], [7], [8], none of these parameters directly reflects the magnitude of ischaemic insult or reliably predicts outcomes after cardiac arrest.

Phosphate is an essential element that plays a crucial role in multiple physiological processes including cellular signal transduction, mineral metabolism, and energy exchange. Several studies have demonstrated that serum phosphate level increases after cardiac arrest [9], [10], [11], though this is not well recognised. Makino et al. [10] compared the acid-base and electrolyte variables of 105 cardiac arrest patients with those of 28 mildly traumatised patients, and reported higher phosphate levels among the cardiac arrest patients. Experimental and clinical studies have suggested that the extent of increase in the phosphate level after ischaemia is directly proportional to the severity of ischaemic injury [11], [12]. Given the relationship between phosphate level and the severity of ischaemic injury shown in previous studies [11], [12], it is plausible that higher phosphate levels may be associated with worse outcomes in cardiac arrest patients. So far, a few studies have evaluated the relationship between initial serum phosphate levels and outcomes in cardiac arrest patients [13], [14]. However, these studies included only small numbers of patients or did not look into the association between phosphate level and outcome using multivariate analysis.

In the present study, we therefore sought to investigate the prognostic value of serum phosphate level in a larger cohort of adult cardiac arrest patients. We hypothesised that serum phosphate level obtained after ROSC would be associated with outcome in cardiac arrest patients.

Section snippets

Study design, population, and setting

This study was a retrospective observational cohort study of adult cardiac arrest patients treated at Chonnam National University Hospital, a university-affiliated, 1005-bed hospital located in Gwangju, Korea, from January 2008 to June 2017. The Institutional Review Board of the Chonnam National University Hospital approved the study protocol (CNUH-2018-004). The need for informed consent was waived because of the retrospective nature of the study.

We included patients aged 18 years or older who

Characteristics of included patients

A total of 923 adult cardiac arrest patients who achieved ROSC were treated during the study period. Of these patients, 249 patients were excluded as shown in Fig. 1. Thus, 674 patients were included in this study and were divided into two groups according to their outcome at hospital discharge; 209 with good outcomes and 465 with poor outcomes. The clinical characteristics stratified by outcome at hospital discharge are shown in Table 1. Patients with poor outcome were older. They had a lower

Discussion

The present study investigated the prognostic value of serum phosphate level in 674 adult patients who were resuscitated following cardiac arrest. Phosphate levels were significantly higher among the patients with poor outcome. The ROC curve of phosphate level yielded an AUC of 0.805 for the prediction of poor outcome. In the multivariate regression model, phosphate level showed a significant association with poor outcome after adjustment for confounders. To the best of our knowledge, this

Conclusions

A higher serum phosphate level after successful resuscitation was independently associated with poor outcome at hospital discharge in adult cardiac arrest patients. However, given the modest prognostic performance of serum phosphate level, it should be used in combination with other prognostic indicators in clinical prognostication of cardiac arrest patients.

Conflicts of interest

All authors have no potential conflicts of interest to disclose.

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The prognostic value of the phosphate-to-albumin ratio in patients with OHCA: A multicenter observational study
2024, American Journal of Emergency Medicine
In patients with out-of-hospital cardiac arrest (OHCA), early and accurate outcome prediction is crucial for making treatment decisions and informing their relatives. A previous study reported an association between high phosphate levels and unfavorable neurological outcomes after return of spontaneous circulation (ROSC); however, its prognostic value was insufficient when used independently. Therefore, this study aimed to validate the usefulness of the phosphate-to-albumin ratio (PAR) in predicting neurological outcomes and in-hospital mortality by incorporating albumin, another known prognostic indicator.
This multicenter observational study included adult OHCA survivors from October 2015 to June 2021. The primary endpoint was an unfavorable neurological outcome at hospital discharge, defined as a cerebral performance category score of 3–5. The in-hospital mortality rates were also evaluated.
Of the 2397 adult OHCA survivors, PAR differed significantly between the unfavorable and favorable neurological outcome groups, as well as between the non-survival and survival to hospital discharge groups (2.4 vs 1.4, 2.5 vs 1.6, respectively). The area under the receiver operating characteristic curve (AUROC) value of the PAR for predicting unfavorable neurological outcome was 0.81 (95% confidence interval [CI], 0.79–0.83), and the AUROC value for predicting in-hospital mortality was 0.76 (95% CI, 0.74–0.78). In multivariable analysis, the PAR was independently associated with unfavorable neurological outcome (odds ratio [OR] 1.30, 95% CI 1.15–1.37; p < 0.001) and in-hospital mortality (OR 1.24, 95% CI 1.12–1.38; p < 0.001).
The PAR is a readily obtainable and independent prognostic indicator for patients with ROSC after OHCA, helping healthcare providers in predicting outcomes.
A non-linear positive relationship between serum phosphate and clinical outcomes in sepsis
2022, Heliyon
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Several possible mechanisms may be explained for our results. First, sepsis usually causes organ ischemic injury and cell damage, resulting in the release of phosphate into circulation [31]. Second, increased levels of serum phosphate is capable of producing more reactive oxygen species through disrupted mitochondrial function, which can aggravate the dysfunction of microcirculation and ischemia of organ [32].
This study aimed to evaluate the possible relationship between serum phosphate and short-term outcomes in sepsis.
This was a retrospective study. Sepsis patients in MIMIC-IV database were included. Based on the quartiles of serum phosphate, all sepsis patients were divided into four groups. Univariable and multivariable regression analyses were constructed for discussing the relationship between different parameters and 30-day mortality in sepsis. A generalized additive model was performed for exploring the association of serum phosphate with 30-day mortality.
6251 sepsis patients including 4368 survivors and 1883 non-survivors were included. A significant relationship between serum phosphate and 30-day mortality was found after adjusting for all potential confounders (OR = 1.19, 95%CI:1.13–1.26, P < 0.0001). The relationship was non-linear with an inflection point of 6.8 mg/dl. On the left side of the inflection point (≤6.8 mg/dl, n = 5911 (94.56%)), the OR was 1.24 (95%CI: 1.17–1.31, P < 0.0001). On the right side of the inflection point (>6.8 mg/dl, n = 340 (5.44%)), the OR was 0.94 (95%CI:0.78–1.13, P = 0.5038).
A non-linear positive relationship was found between serum phosphate and 30-day mortality in sepsis. Serum phosphate was associated with mortality in sepsis. Our results could be used for screening out those sepsis patients with higher risk of worse outcomes.
Rearrest during hospitalisation in adult comatose out-of-hospital cardiac arrest patients: Risk factors and prognostic impact, and predictors of favourable long-term outcomes
2022, Resuscitation
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This suggests that the time to ROSC after OHCA and that to ROSC after rearrest together contribute to unfavourable outcomes. Further, we found that hypophosphataemia within 7 d was associated with favourable outcomes, which is consistent with previous study findings suggesting the association between higher phosphate levels after ROSC and unfavourable outcomes.29,35 In our study, neither the body temperature nor the TTM phase at the time of rearrest was associated with the outcome.
Rearrest occurs commonly after initial resuscitation following out-of-hospital cardiac arrest (OHCA). We determined (1) the predictors of rearrest during hospitalisation that can be identified in the hours immediately after OHCA, (2) the association between rearrest and favourable long-term outcomes, and (3) the predictors of favourable long-term outcomes in rearrest patients.
Conditional multivariable logistic regression analyses were performed using the Korean Hypothermia Network prospective registry data, which included details of adult OHCA patients treated with targeted temperature management at 22 teaching hospitals in South Korea.
Among the 1,233 patients, 260 (21.1%) experienced rearrest. Of the 192 patients resuscitated from first rearrest, 33 (17.2%) achieved 6-month favourable outcomes. Arrhythmia, heart failure, ST-segment elevation, lower initial Glasgow coma scale (GCS) motor score, higher initial lactate level, and antiarrhythmic drug use within 1 h were independently associated with rearrest. Higher lactate level and antiarrhythmic drug use were associated with shockable first rearrest, while arrhythmia, heart failure, ST-segment elevation, and lower GCS motor score were associated with non-shockable first rearrest. Rearrest was independently associated with a lower likelihood of 6-month favourable outcomes (P = 0.003). Initial shockable rhythm after OHCA, absence of diabetes, shorter cumulative time to restoration of spontaneous circulation, coronary angiography, and hypophosphataemia within 7 d were independently associated with 6-month favourable outcomes in the patients resuscitated from first rearrest.
Rearrest during hospitalisation after OHCA was inversely associated with 6-month favourable outcomes. We identified several risk factors for rearrest and prognostic factors for patients resuscitated from first rearrest.
Association between ion shift index and prognosis in severe trauma patients without isolated head injury: Ion shift index and prognosis in severe trauma patients
2021, Injury
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Previous studies have reported that the size of the ion shift is proportional to the severity of ischemic injury and that disturbances in ion homeostasis persist even after recovery when the injury is severe [29, 30]. Previous studies on cardiac arrest patients reported that phosphate and ISI can be used as key variables in predicting prognosis [12, 21]. High phosphate and ISI in the blood may be indicators of damage to energy-dependent homeostatic mechanisms at the cellular level.
This study aimed to investigate the ion shift index (ISI) as a prognostic factor of severe trauma. We hypothesized that the initial ISI measured in the emergency department (ED) is associated with discharge survival in severe non-isolated head injury (IHI) patients.
This retrospective observational study included severe trauma patients with available medical records from January 2017 to December 2018 but excluded those with IHI. Logistic regression analysis was conducted to identify the risk factors for mortality in non-IHI patients, and adjustments were performed for relevant covariates. An area under the receiver operating characteristics curve (AUROC) analysis was performed to examine the primary outcome of our study, which was mortality at hospital discharge in severe non-IHI trauma patients.
Of the 483 severe non-IHI trauma patients included in the study, 86 patients (17.8 %) died. The multiple logistic regression analysis demonstrated ISI (odds ratio [OR], 2.300; 95% CI, 1.183–4.470) was significantly associated with mortality in the non-IHI group. Additionally, trauma and injury severity score (TRISS; OR, 0.538; 95% CI, 0.447–0.649), lactate (OR, 1.410; 95% CI, 1.252–1.588), creatinine (OR, 1.554; 95% CI, 1.221–1.979), and activated partial thromboplastin time (aPTT; OR, 1.050; 95% CI, 1.021–1.080) were independently associated with mortality at hospital discharge. The AUROC values for TRISS, lactate, aPTT, creatinine, and ISI were as follows: 0.892 (95% CI, 0.861–0.918), 0.838 (95% CI, 0.803–0.870), 0.754 (95% CI, 0.712–0.792), 0.650 (95% CI, 0.606–0.693), and 0.848 (95% CI, 0.813–0.879), respectively. The AUROC for the multiple logistic regression model with ISI was 0.942 (95% CI, 0.917–0.962). In a model in which TRISS was omitted, the addition of ISI to other predictors significantly improved the AUROC to 0.900 (95% CI, 0.869-0.925) (p=0.039).
The initial ISI in the ED after trauma was associated with mortality in severe non-IHI trauma patients. In conjunction with other prognostic indicators, it could be used as an early prognostic marker, particularly if TRISS is unavailable.
PROLOGUE (PROgnostication using LOGistic regression model for Unselected adult cardiac arrest patients in the Early stages): Development and validation of a scoring system for early prognostication in unselected adult cardiac arrest patients
2021, Resuscitation
Citation Excerpt :
The CPC score was determined through medical record review conducted by an investigator who was blinded to the objective of this study. Furthermore, we collected levels of laboratory parameters known as outcome predictors (arterial pH,16,17 haemoglobin,18,19 C-reactive protein,20 creatinine,21,22 glucose,23 albumin,24,25 potassium,17,26 phosphate,26 calcium,24 magnesium,27 and lactate28) using the first available laboratory data after ROSC. To compare the performance of our model with those of existing cardiac arrest-specific scoring models, the OHCA and cardiac arrest hospital prognosis (CAHP) scores were calculated for patients with witnessed OHCA,5,6 and the C-GRApH score presented by Kiehl et al.7 was calculated for OHCA patients who underwent TTM.
Early prognostication after cardiac arrest would be useful. We aimed to develop a scoring model for early prognostication in unselected adult cardiac arrest patients.
We retrospectively analysed data of adult non-traumatic cardiac arrest patients treated at a tertiary hospital between 2014 and 2018. The primary outcome was poor outcome at hospital discharge (cerebral performance category, 3–5). Using multivariable logistic regression analysis, independent predictors were identified among known outcome predictors, that were available at intensive care unit admission, in patients admitted in the first 3 years (derivation set, N = 671), and a scoring system was developed with the variables that were retained in the final model. The scoring model was validated in patients admitted in the last 2 years (validation set, N = 311).
The poor outcome rates at hospital discharge were similar between the derivation (66.0%) and validation sets (64.3%). Age <59 years, witnessed collapse, shockable rhythm, adrenaline dose <2 mg, low-flow duration <18 min, reactive pupillary light reflex, Glasgow Coma Scale motor score ≥2, and levels of creatinine <1.21 mg dl⁻¹, potassium <4.4 mEq l⁻¹, phosphate <5.8 mg dl⁻¹, haemoglobin ≥13.2 g dl⁻¹, and lactate <8 mmol l⁻¹ were retained in the final multivariable model and used to develop the scoring system. Our model demonstrated excellent discrimination in the validation set (area under the curve of 0.942, 95% confidence interval 0.917–0.968).
We developed a scoring model for early prognostication in unselected adult cardiac arrest patients. Further validations in various cohorts are needed.
Ion shift index as a promising prognostic indicator in adult patients resuscitated from cardiac arrest
2019, Resuscitation
Citation Excerpt :
These findings suggest that the ion shift index levels can be used for prognostication regardless of these factors. Our study findings are in line with the results of previous studies that reported significant associations between serum electrolyte levels and outcomes after cardiac arrest.18,19 In an observational study including 98 cardiac arrest patients, Skrifvars et al. reported that a higher serum potassium level during the first 72 h was independently associated with higher mortality.18
Several studies reported that disturbances in cellular ion homeostasis occur following ischaemia, the magnitude of which was proportional to illness severity. The changes in serum electrolyte levels following ischaemia were minor compared with the changes in ion concentrations in the extracellular fluid. To amplify the serum electrolyte changes, we devised a new index (ion shift index), which could be calculated using commonly measured serum electrolyte levels, and explored its prognostic value in adult cardiac arrest patients.
This retrospective observational study included adult cardiac arrest survivors treated at a tertiary university hospital between January 2014 and December 2017. Using the first available serum electrolyte levels, the ion shift index was calculated as follows: ion shift index = (potassium + phosphate + magnesium) / calcium. The primary outcome was poor outcome at hospital discharge (cerebral performance categories 3–5).
The area under the receiver operating characteristic curve (AUC) of ion shift index for predicting poor outcome was 0.878 (95% confidence interval [CI], 0.849–0.907). The AUC of ion shift index was greater than those of individual electrolytes (all p < 0.001). In multivariate analysis, higher ion shift index levels were independently associated with poor outcome (odds ratio, 2.916; 95% CI, 1.798–4.730; p < 0.001). The AUC of multivariate model including ion shift index was greater than that of multivariate model after excluding ion shift index (p = 0.007).
Our results suggest that the ion shift index can be helpful in the early prognostication of adult cardiac arrest patients.

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^☆: A Spanish translated version of the abstract of this article appears as Appendix in the final online version at https://doi.org/10.1016/j.resuscitation.2018.04.026.

^☆☆: Chonnam National University Hospital Institutional Review Board Protocol No. CNUH-2018-004.

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Clinical paperPrognostic value of serum phosphate level in adult patients resuscitated from cardiac arrest☆,☆☆

Abstract

Background

Methods

Results

Conclusions

Introduction

Section snippets

Study design, population, and setting

Characteristics of included patients

Discussion

Conclusions

Conflicts of interest

Resuscitation

Resuscitation

Resuscitation

Resuscitation

Clin Chim Acta

J Emerg Med

Am J Emerg Med

Am J Emerg Med

Resuscitation

Am J Emerg Med

Resuscitation

Resuscitation

Resuscitation

Am J Kidney Dis

Kidney Int

Am J Cardiol

Am J Emerg Med

Sudden cardiac death: epidemiologic and financial worldwide perspective

J Interv Card Electrophysiol

Clinical paper
Prognostic value of serum phosphate level in adult patients resuscitated from cardiac arrest☆,☆☆