Predictive performance of PiCCO system and blood gas parameters for early prognosis of patients with sepsis

doi:10.21203/rs.3.rs-49021/v1

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Predictive performance of PiCCO system and blood gas parameters for early prognosis of patients with sepsis

https://doi.org/10.21203/rs.3.rs-49021/v1

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Purpose: Invasive hemodynamics monitor directed fluids resuscitation remains misgiving issues. This study aims to explore the predictive value of the PiCCO system (pulse indicator continuous cardiac output device) and blood gas parameters on the early prognosis of patients with sepsis.

Methods: 42 patients with sepsis were included from January 2013 to January 2015. All patients were stratified into survivor group (n=29) and nonsurvivor group (n=13) based on seven day-mortality. The PiCCO and blood gas parameters at enrollment and 24 hours were compared between two groups. The predictive performance of these parameters was distinguished with Area Under the Receiver Operating Characteristic Curve (AUC).

Results: At 24 hours after enrollment, the HR (97.27±22.07 vs. 120.20±20.56), extravascular lung water index (EVLWI) (7.32±2.96 vs. 15.9±11.2), and lactic acid (Lac) (1.62±0.92 vs. 6.33±5.83) level were significantly lower in survivor group (P < 0.05), whereas the cardiac index (CI) (3.67±0.85 vs. 2.98±0.73) and PaO₂/FiO₂ (242.8±89.68 vs.136.07±78.01) increased significantly. Meanwhile PaO₂/FiO₂ was negatively correlated with EVLWI (r= -0.673, P < 0.01). The AUC of the combination of Lac with PaO₂/FiO₂, HR, EVLWI, pulmonary vascular permeability index (PVPI) and Lac at 24 hours were 0.853, 0.739, 0.776, 0.764, and 0.794.

Conclusions: The PiCCO and blood gas parameters exhibit superior predictive capability for early prognosis in patients with sepsis, and the combination Lac with PaO₂/FiO₂ was noninferior under the circumstance of unavailability with PiCCO.

Internal Medicine

Critical Care & Emergency Medicine

sepsis

early prognosis

PiCCO

blood gas

Although numerous therapeutic approaches have been employed, sepsis remains one of the major causes of death in the intensive care unit (ICU)[1]. As recommended by the Surviving Sepsis Campaign guidelines, early fluid resuscitation occupies the core of the therapeutic bundle[2]. Nevertheless, the contrary pieces of the evidence challenge the reliability of the fluid treatment. Fluid overload can increase the risk of organ dysfunction, including acute lung injury and acute renal injury, thus lead to high mortality[3]. Hence, it is crucial to ensure fluid balance based on the stable circulation system.

The PiCCO (Pulse index continuous cardiac output) system as the representative of invasive techniques permits the monitoring of hemodynamic status including vascular tone, fluid load and cardiac function, following responding comprehensively physiological condition, such as fluid responsiveness, oxygenation and pulmonary oedema. Although the application of PiCCO emerged promptly in recent times, some disputes remain yet clarified. Whether the static parameters derived from PiCCO can present full disclosure of the volume evolution, the threshold of some settings can be the best guidance to clinical practice, and this technique can authentically improve or predict the clinical outcomes[4]. Furthermore, the risk of invasive manipulation and high expense under some circumstance drive the implementation of PiCCO into irresolute. The blood gas analysis, as a routine laboratory test characterized by easy accessibility, minimally invasiveness, and low price, still keep strong vitality to assess the oxygenation status and acid-base balance for critically illness patients[5].

We conducted this study to reflect the forecast value of PiCCO system on early clinical outcome in patients with sepsis and further compare the link between PiCCO with blood gas parameters.

Study design

This retrospective study was performed in a 29-bed mixed adult ICU at a tertiary teaching hospital from January 2015 to January 2018. The hospital ethics committee endorsed this study.

Study Participants

This study encompassed 51 adult patients (age ≥ 18 years) who met the clinical criteria of sepsis in Sepsis-2 consensus definitions[6]. Subjects were discarded meeting one of the following conditions: admission owing to trauma, pregnancy, or poison, under treatment with immunosuppressant agents, chemotherapy or radiotherapy within 30 days before inclusion, and refusal to cardiopulmonary resuscitation.

Intervention

After all patients diagnosed with sepsis, the clinicians instantly initiated the treatment of Surviving Sepsis Campaign Bundle, including obtaining microbial samples from infectious sites, administration of broad-spectrum antibiotics, fluid resuscitation, commence a vasopressor titration et cetera. Prior to fluid infusion, all cases were implemented with PiCCO device, and the PiCCO survey was executed at least every 8 hours, or depended on the clinician decision when the drastic vital sign change. Blood gas analysis was obtained along with every PiCCO inquiry.

Data collection

According to seven day survival or not after enrollment, all patients were classified into survivor group (n=29) and nonsurvivor group (n=13). The following clinical characteristics were assembled: sex, age, infection position, underlying disease, such as hypertension, chronic cardiovascular disease, chronic obstructive pulmonary disease, chronic renal failure, and diabetes mellitus. Meanwhile the Acute physiology and chronic health practical guidance system II (APACHE II) and the Sequential Organ Failure Assessment (SOFA) score were calculated for patient within first 24 hours.

Statistical analysis

Data were represented with either frequency and percentage for categorical variables or mean and standard deviation (SD) and interquartile range (IQR) for continuous variables. Two groups were compared with the t test or the the non-parametric Mann-Whitney U test, as appropriate. Dependency relationships among the hemodynamic and blood gas parameters were identified by person correlation analysis. All parameters exhibited significant difference in comparison were further evaluated for the predictive value via receiver-operating characteristic (ROC). All data processing and statistical analyses were performed with SPSS 13.0.

After totally screening, 42 patients (29 males, 13 females) were fulfilled with inclusion criteria (Fig. 1), of whom 13 (30.1%) died after 7 days. And further follow-up revealed a 28-day mortality rate as 42.9% (18/42). Table 1 shows there are no significant differences between the survivors and nonsurvivors in terms of baseline demographic and clinical characteristics. Comparison to nosurvivor group, at 24 hours after enrollment, the HR (97.27±22.07 vs. 120.20±20.56), EVLWI (7.32±2.96 vs. 15.9±11.2), and Lac (1.62±0.92 vs. 6.33±5.83) level in survivor group exhibits considerably lower (P < 0.05), whereas the CI and PaO₂/FiO₂ were higher (Table 2). Person correlation analysis revealed PaO₂/FiO₂ was negatively correlated with EVLWI (r = -0.673, P < 0.01) at 24 hours (Fig. 2), in addition Lac was found no correlation with CI.

Table 1. Demographic data and clinical characteristics according to survival at day 7

	Survivors (n=29)	Nonsurvivors (n=13)	P value
Age (years)	63 ± 13	66 ± 17	0.572
Males, n (%)	19 (65.5)	13 (76.9)	0.086
APACHEⅡ	21 ± 3	25 ± 5	0.545
SOFA	11 ± 3	14 ± 3	0.152
Underlying disease, n(%)
Hypertension	11 (37.9)	7 (53.8)	0.272
Chronic cardiovascular disease	15 (51.7)	8 (61.5)	0.742
COPD	3 (10.3)	1 (7.6)	0.520
Chronic renal failure	4 (13.8)	4 (30.8)	0.221
Diabetes mellitus	4 (13.8)	5 (38.4)	0.182
Source of infection, n(%)
Lungs	15 (51.7)	9 (69.2)	0.284
Abdomen	11 (37.9)	3 (23.1)	0.709
Soft tissue	2 (6.9)	1 (7.7)	1.000
Other	1 (4.3)	0 (0)	0.485

APACHE II, Acute physiology and chronic health practical guidance system II; SOFA, Sequential Organ Failure Assessment; COPD, chronic obstructive pulmonary disease

Table 2. Comparison of hemodynamic parameters at beginning and 24 hours after enrollment between survivors and norsurvivos

Hemodynamic parameter	Time	Survivors (n=29)	Nonsurvivors (n=13)	t	P
HR (bpm)	Baseline	123.73 ± 17.56	123.93 ± 28.97	0.320	0.751
HR (bpm)	24 h	97.27 ± 22.07	120.20 ± 20.56	−2.945	0.006
CI (ml·s⁻¹·m⁻²)	Baseline	3.89 ± 1.48	3.62 ± 1.80	0.445	0.660
CI (ml·s⁻¹·m⁻²)	24 h	3.67 ± 0.85	2.98 ± 0.73	2.395	0.024
EVLWI (ml·kg⁻¹)	Baseline	8.98 ± 5.85	13.2 ± 7.39	−1.162	0.120
EVLWI (ml·kg⁻¹)	24 h	7.32 ± 2.96	15.9 ± 11.2	−2.870	0.008
SVI (ml·m⁻²)	Baseline	31.67 ± 10.56	29.53 ± 13.95	0.472	0.640
SVI (ml·m⁻²)	24 h	41.31 ± 14.93	45.51 ± 66.09	−0.239	0.813
GEF (%)	Baseline	17.80 ± 4.74	15.80 ± 5.34	1.084	0.228
GEF (%)	24 h	19.40 ± 5.26	16.53 ± 5.29	1.488	0.148
GEDVI (ml·m⁻²)	Baseline	764.46± 89.13	787.57 ± 330.30	−0.221	0.827
GEDVI (ml·m⁻²)	24 h	898.07± 34.99	754.31 ± 166.55	1.821	0.081
CVP (cmH₂O)	Baseline	9.80 ± 4.20	9.33 ± 2.38	0.375	0.710
CVP (cmH₂O)	24 h	9.33 ± 5.70	9.33 ± 2.74	0.000	0.740
SVRI (kPa·s·L⁻¹·m⁻²)	Baseline	1602.13± 647.15	1706.27± 1011.97	−0.336	0.740
SVRI (kPa·s·L⁻¹·m⁻²)	24 h	1789.07± 419.84	1515.87± 612.63	1.425	0.165
PVPI	Baseline	1.89 ± 0.94	2.43 ± 1.03	−1.498	0.145
PVPI	24 h	1.30 ± 0.46	2.87 ± 1.89	−3.119	0.004
Lac (mmol/L)	Baseline	5.61 ± 3.85	5.11 ± 2.94	0.385	0.703
Lac (mmol/L)	24 h	1.62 ± 0.92	6.33 ± 5.83	−2.885	0.008
PaO₂/FiO₂ (mmHg)	Baseline	202.0 ± 148.0	233 ± 142.60	−0.584	0.564
PaO₂/FiO₂ (mmHg)	24 h	242.8 ± 89.68	136.07 ± 78.01	3.478	0.002
BE (mmol/L)	Baseline	−4.33 ± 4.72	−4.08 ± 6.92	−0.119	0.906
BE (mmol/L)	24 h	1.47 ± 2.64	−3.64 ± 6.99	2.650	0.013

HR, heart rate; CI, cardiac index; EVLWI, extravascular lung water index; SVI, stroke volume index;

GEF, global ejection fraction; GEDVI, global end-diastolic volume index; CVP, central venous pressure; SVRI, systemic vascular resistance index; PVPI, pulmonary vascular permeability index; BE, base excess

As shown in Table 3, the AUC-ROC of HR, EVLWI, PVPI, and Lac were 0.739, 0.776, 0.764, and 0.794. Compared to the single parameter, the combination of Lac and PaO₂/FiO₂ at 24 hours was superior for early prognosis. The AUC was 0.853, with a sensitivity of 83.3%, a specificity of 84.6%, and the Youden’ s Index of 0.679, as seen in Figure 3.

Table 3. The predictive value of hemodynamic parameters for early prognosis

Parameter	AUC	Critical value	Sensitivity (%)	Specificity (%)	Youden’s index	P
HR (24h)	0.739	116.5	66.7	86.7	0.534	0.007
CI (24h)	0.302	2.94	33.3	13.3	−0.534	0.065
EVLWI (24h)	0.776	9.2	53.3	86.7	0.534	0.010
PVPI (24h)	0.764	2.05	57.1	93.3	0.504	0.015
Lac (24h)	0.794	2.75	66.7	92.3	0.590	0.002
PaO₂/FiO₂ (24h)	0.171	141.0	33.3	70.0	−0.600	0.002
BE (24h)	0.267	−3.1	46.7	0.0.	0.533	0.029

HR, heart rate; CI, cardiac index; EVLWI, extravascular lung water index;

PVPI, pulmonary vascular permeability index; BE, base excess

The main fact of this study is that certain hemodynamic or blood gas parameters measured at 24 h after sepsis onset were associated with worse early clinical outcomes.

Although the absolute mortality has decreased from 35.0% to 18.4% in patients with severe sepsis in the areas of Australia and New Zealand during the last decades[7], one recent systematic review revealed the ICU mortality of sepsis in Europe and North America remains 37.3%, where the morbidity was estimated at 10.4%[8]. It is similar to these studies that the 28-day mortality was 42.9% in our study. The factor that average age over 65 in our patient population could contribute to the relatively high mortality, according to the results from some surveys launched in China[1,9].

To date, the lack of recognition in the underlying pathophysiology mechanism falls us into the dilemma of treatments for sepsis, of which to maintain the stable hemodynamics occupy the critical core in the early period. In order to achieve the goal of volume status fulfilled with oxygen delivery-consumption balance, active fluid resuscitation is always the basis of treatment bundle; meanwhile, the varied methods to monitor the fluid infusion could overcome some side-effects perhaps to follow, such as pulmonary edema or cardiac overload.

Due to those significant drawbacks, including air embolism, permanent occlusion, pseudoaneurysm and so on, occurred in fewer than 1% of the clinical procedures, PiCCO has been the invasive hemodynamic monitor system generally accepted[10]. The fluid challenge strategics directed via PiCCO present fully compatible with the philosophy of titration therapy. It is a remarkable fact that numerous actively advocated studies virtually focus on one or more specific parameters yield from the PiCCO techniques rather than itself[11]. Theoretically, the ability to integrate a series of hemodynamic data provide the most valuable advantage of PiCCO; however, the misinterpretation of these data causes the wrong direction of treatment. Zhang et al. asserted that the fluid management schedule based on PiCCO parameters couldn’t improve the clinical outcome in patients with sepsis and/or acute respiratory distress syndrome[4]. Conversely, Sánchez-Sánchez argued that the improper diagnostic criteria for the intrathoracic blood volume index (ITBVI) led the negative conclusion in Zhang’s study[12], which alert the clinical practitioners should be cautious about PiCCO data analysis. But as shown in our research and the other similar studies, the EVLWI and PVPI among the PiCCO parameters exhibited the outstanding predictive power for the prognosis in patients with sepsis[13].

Despite many apparent advantages of the invasive hemodynamic monitor, it doesn't mean that inexpensive examination could be neglected. We found that EVLWI exerted significant correlation with oxygenation index, which calculated based on the data from blood gas. EVLWI reflects the situation that the liquid content extravasate outside of the pulmonary vasculature into pulmonary alveolar and interstitium, following by ventilation-perfusion imbalance. Some pathophysiological factors, including lung resection, pulmonary vessels obstruction, and higher positive end-expiratory pressure, may potentially generate the trust-less data of EVLWI[14]. PaO2/FiO2 and Lac widely verified in the multiple intensive care scenarios[15-17], likewise present the affordable alternatives to invasive methods in our results, especially combined both themselves.

Several limitations should be clarified when the application of our instructional results, containing retrospective study design, small sample size, and patients population confined to sepsis. Even if considering these deficiencies, our study offers another non-inferior choice for prediction of the patients with sepsis under the circumstance without costly PiCCO system.

The hamodynamic parameters including HR, EVLWI, and PVPI exhibit superior predictive performance for early prognosis in patients with sepsis, and the combination Lac with PaO₂/FiO₂ possess identical diagnostic value.

Availability of data and materials

All data generated or analyzes during this study are included in this article .

Acknowledgements

Authors are grateful to all subjects for participating in this study. Authors are also grateful for comments from reviewers which are valuable for improving manuscript.

Authors’ information

Jing Yuan and XueMei Qin contributed equally to this work.

Affiliations

Department of Critical Care Medicine, Yijishan Hospital, First Affiliated Hospital of Wannan Medical College, 2# Zheshan Road, Wuhu 241001, China

Jing Yuan, XueMei Qin, Tao Wang, Tong Wang, Jingyi Wu, Guanggui Shen, Yingya Cao, Weihua Lu, Zhen Wang

Contributions

Y. and Z.W. designed the present study. Data analysis was conducted by J.Y. and XM.Q. All the authors were involved in the execution of the present study. All the authors participated in preparation of the manuscript and approved its final version for publication.

Ethics approval and consent to participate

Ethical approval was obtained from Scientific Research IRB of Wannan Medical College Yijishan Hospital(number: 2015018; approved Nov 18, 2015). Each participant provided written informed consent, and our study conformed to the Declaration of Helsinki.

Consent for publication

Not applicable.

Funding

The study was supported by Anhui Provincial Natural Science Foundation for Youth (1908085QH360), by Funding of "Peak" Training Program for Scientific Research of Yijishan Hospital, Wannan Medical College (GF2019G08) and by The open project of Key Laboratory of Non-coding RNA Transformation Research of Anhui Higher Education Institution (Wannan Medical College) (RNA201910).

Conflicts of interest

The authors declare that they have no competing interests.

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Predictive performance of PiCCO system and blood gas parameters for early prognosis of patients with sepsis

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