Fluid resuscitation based on pulse contour cardiac output monitoring is associated with improved prognosis in adult severe burn patients: a retrospective cohort study
Introduction
Acute burn injury is a very common form of trauma, with high rates of morbidity and mortality. In China, it has been reported that about 26 million people suffer from different degrees of burns and scalds every year (1), and globally, burns can cause about 330,000 deaths each year (2). In cases of severe burns, the homeostasis of the body will be disrupted due to stress reactions and subsequent infection. Multiple types of inflammatory related factors are released from immune cells, resulting in increased capillary permeability (3), and a large amount of body fluids will be transferred from the blood vessel to the intercellular space, resulting in insufficient volume of circulating blood. Therefore, burns patients are very prone to hypovolemia and shock (4), which can lead to organ dysfunction or failure, such as acute kidney injury (AKI) and acute respiratory distress syndrome (ARDS). It has been reported that about 30% of major burns patients have AKI as well as ARDS during the period of fluid resuscitation, and the occurrence of AKI and ALI further worsens patient outcomes (5,6).
Timely fluid resuscitation is very important for the treatment of severe burns patients, especially within the first 8 to 24 hours (7). However, there is a lack of unified fluid resuscitation formulas and protocols, and controversy remains as to how this should be conducted. While common fluid resuscitation formulas used globally include modified parkland, modified Brooke, Evans, Muir Barclay, and Haifa formula (8), in recent years, the formula of the Third Military Medical University (TMMU) has been widely applied in China (9). Most formulas currently used are crystalloid-based, which can obtain certain curative effect, although there are some differences in their mechanism and effect (10). While current liquid resuscitation formulas mostly focus on the initial stage of liquid resuscitation, it may be inappropriate to perform this according to any one formula in the later stage of severe burns. Insufficient fluid will aggravate hypovolemic shock and organ failure, and excessive fluid will also increase the incidence of infection complications (11,12). Therefore, a monitoring method is required to further guide fluid resuscitation in the late stage of severe burns.
Cardiac output (CO) is usually monitored by pulmonary artery thermodilution using a pulmonary artery catheter to assess hemodynamic instability in critically ill patients, including severe burns patients (13). However, the safety of pulmonary artery catheterization is still controversial, and less invasive methods for CO monitoring are yet to be fully developed. Pulse contour cardiac output (PCCO) analysis is a new minimally invasive technique which has emerged in recent decades (14). The single thermal indicator technique is used in PCCO to calculate volumetric parameters of CO using a modified Wesseling algorithm (15), and has been beneficial to patients with acute and chronic heart failure and constrictive pericarditis (16-18). However, there are no related studies investigating the effects of PCCO monitoring on the prognosis of adult severe burns patients.
Therefore, we performed this single center retrospective study to analyze the effects of PCCO monitoring on the prognosis of adult patients with severe burns using multivariable logistic regression. It was hypothesized that the application of PCCO monitoring would decrease total mortality and the incidence of burn-related complications in severe burns patients and may also shorten the length of hospital stay. We present the following article in accordance with the STROBE reporting checklist (available at https://dx.doi.org/10.21037/apm-21-2587).
Methods
Patients and study design
This was a retrospective study performed in a single center of the Affiliated Hospital of Jiangnan University enrolling patients from January 2015 to December 2020. The inclusion criteria were as follows: patients older than 18 years and younger than 80 years, admitted to our hospital within 8 hours after burn injury, with a total burn surface area (TBSA) larger than 40%, and without life-threatening comorbid diseases. The exclusion criteria were as follows: patients who died within 24 hours after admission, those given palliative comfort care only, and those without complete data. Based on the treatment pattern they received, enrolled patients were divided into a control group receiving fluid resuscitation and conventional monitoring, and a study group receiving fluid resuscitation and PCCO monitoring. All procedures performed in this study involving human participants were in accordance with the Declaration of Helsinki (as revised in 2013). The study was approved by institutional ethics committee of Affiliated Hospital of Jiangnan University (No. 2021011). Individual consent for this retrospective analysis was waived.
Fluid resuscitation protocol
Fluid resuscitation was performed in enrolled patients according to the TMMU formula (19). In detail, the volume of fluid given in the first 24 hours was calculated as 1.5 mL/kg/% TBSA + 2,000 mL, and 0.75 mL/kg/% TBSA +2,000 mL of fluid was then given in the second 24 hours. Lactated Ringer’s solution was the first choice of crystalloid and frozen plasma or 5% albumin solution was selected as the colloid, with a ratio of crystalloid to colloid of 2:1. An extra 2,000 mL of 5% glucose solution was used as the basic requirement of the body for water. After this, the strategy of fluid resuscitation in the control group was adjusted according to clinical parameters during the treatment, including heart rate, blood pressure, urine volume, respiratory rate, and SpO2, while PCCO provided some additional clinical parameters in the study group, including global end-diastolic volume index, intrathoracic blood volume index, cardiac index, system vascular resistance index, and extravascular lung water index, which were also used to adjust the fluid resuscitation strategy.
Data collection
The demographic and clinical data of patients in the two groups collected at admission were as follows: age, sex, body weight, etiology of burn injury, TBSA, area of full thickness burn, inhalation injury, time to resuscitation, and chronic comorbid diseases. Baseline data of urine output, serum creatinine (sCr), blood urea nitrogen (BUN), creatine kinase-MB (CK-MB), and procalcitonin (PCT) were also collected. Resuscitation fluid volume ratio, crystalloid volume ratio, and colloid volume ratio (mL/kg/% TBSA) in the first and second 24 hours postburn were then collected in both groups.
Outcome measurements and definitions
The primary outcomes in this study were 28-day mortality and total mortality of enrolled patients, while the secondary outcomes included burn-related complications, such as AKI, ARDS, sepsis, and venous thromboembolism, and the length of hospital stay and ICU stay. The incidence of AKI was defined as an increase in sCr of at least 26.4 μmol/L over the baseline, or an increase in sCr of at least two-fold over the baseline. The incidence of ARDS was defined according to the Berlin definition (20).
Statistical analysis
All statistical analysis was performed using SPSS 18.0 (IBM corporation, NY, USA). Continuous variables were expressed by mean with standard deviation and compared by t-test, and binary variables were expressed by number with percentage and compared using chi-square test. Multivariable logistic regression analysis was performed to determine the risk factors of mortality and burn-related complications in enrolled patients, and multivariable linear regression analysis was performed to investigate the relationship between the use of PCCO monitoring and length of hospital stay. P values less than 0.05 were considered statistically significant.
Results
More than 550 patients were admitted to our hospital due to burn injury between January 2015 and December 2020. Of these, 320 were diagnosed as having severe burns and 5218 patients were excluded. A further 129 patients were excluded due to incomplete data and early death, and 191 patients were finally enrolled. According to the treatment pattern they received, 109 patients were placed into a control group and 82 patients into a study group (Figure 1).
Table 1 shows the characteristics of patients. The mean age was 42.5±12.4 years in the control group and 41.0±12.1 years in the study group, showing no significant difference (P=0.402). Most patient in both groups were male, constituting more than 75% of the total, and their mean body weight was 63.2±9.8 kg in the control group and 61.3±11.7 kg in the study group, showing no significant difference (P=0.209). About 90% of the severe burns in this study were caused by flame. While the TBSA was slightly higher in the study group than in the control group, showing no significant difference, the area of full thickness burn was much higher in the control group than in the study group (P=0.021). Inhalation injury after burn injury was seen in 42 and 39 patients in the control and study groups, respectively, and the time to resuscitation was about 5 hours in both groups. Although some patients had one or two comorbid diseases, there was no significant difference between the two groups. Baseline data of urine output and lab characteristics in both groups are shown in Table 2, and while the baseline level of sCr and BUN was slightly higher in the control group compared with the study group, no significant difference was found (P=0.081 and 0.089).
Table 1
| Characteristics | Control group | Study group | P value |
|---|---|---|---|
| Number | 109 | 82 | |
| Age (years) | 42.5±12.4 | 41.0±12.1 | 0.402 |
| Sex | 0.887 | ||
| Male | 86 (78.9%) | 64 (78.0%) | |
| Female | 23 (21.1%) | 18 (22.0%) | |
| Body weight (kg) | 63.2±9.8 | 61.3±11.7 | 0.209 |
| Etiology of burn injury | 0.324 | ||
| Flame | 98 (89.9%) | 77 (93.9%) | |
| Hot water | 11 (10.1%) | 5 (6.1%) | |
| TBSA | 53.1±11.6 | 55.2±12.2 | 0.237 |
| Area of full thickness burn | 17.5±6.5 | 15.1±7.4 | 0.021 |
| Inhalation injury | 42 (38.5%) | 39 (47.6%) | 0.211 |
| Time to resuscitation (hours) | 5.0±2.1 | 5.3±2.1 | 0.271 |
| Chronic comorbid diseases | |||
| Hypertension | 18 (16.5%) | 14 (17.1%) | 0.918 |
| Diabetes | 11 (10.1%) | 10 (12.2%) | 0.646 |
| Congestive heart failure | 2 (1.8%) | 3 (3.7%) | 0.635 |
| Cerebrovascular accident | 3 (2.8%) | 3 (3.7%) | 1.000 |
| Chronic obstructive pulmonary disease | 2 (1.8%) | 1 (1.2%) | 1.000 |
TBSA, total burn surface area.
Table 2
| Characteristics | Control group | Study group | P value |
|---|---|---|---|
| Baseline urine output (mL/h) | 66.3±19.4 | 68.0±24.6 | 0.613 |
| Baseline sCr (μmol/L) | 88.3±22.4 | 82.6±22.1 | 0.081 |
| Baseline BUN (mmol/L) | 7.9±1.7 | 7.5±1.5 | 0.089 |
| Baseline CK-MB (U/L) | 78.1±23.9 | 80.0±23.9 | 0.588 |
| Baseline PCT (μg/L) | 1.12±0.22 | 1.13±0.29 | 0.761 |
sCr, serum creatinine; BUN, blood urea nitrogen; CK-MB, creatine kinase-MB; PCT, procalcitonin.
The resuscitation fluid volume ratio, crystalloid volume ratio, and colloid volume ratio are summarized in Table 3. This shows the fluid volume ratio and colloid volume ration were both significantly higher in the control group than the study group in the first 24 hours (both P<0.001), and in the second 24 hours (P=0.007 and 0.003). On the other hand, there was no significant difference between the two groups in crystalloid volume ratio during the period of 48 hours.
Table 3
| Characteristics (mL/kg/% TBSA) | Control group | Study group | P value |
|---|---|---|---|
| First 24 hours | |||
| Resuscitation fluid volume ratio | 2.59±0.39 | 2.29±0.40 | <0.001 |
| Crystalloid volume ratio | 1.00±0.19 | 1.02±0.28 | 0.517 |
| Colloid volume ratio | 0.78±0.27 | 0.52±0.18 | <0.001 |
| Second 24 hours | |||
| Resuscitation fluid volume ratio | 1.90±0.44 | 1.73±0.39 | 0.007 |
| Crystalloid volume ratio | 0.76±0.18 | 0.72±0.24 | 0.147 |
| Colloid volume ratio | 0.40±0.17 | 0.34±0.10 | 0.003 |
TBSA, total burn surface area.
The overall mortality of patients was relatively low with only five patients dying within 28 days and eight dying during treatment (Table 4). More patients had AKI and ARDS in the control group during treatment than in the study group (P=0.029 and 0.016), while about 20% patients in both groups had sepsis and 11 had venous thromboembolism (Table 4). The length of hospital stay in the study group was 59.3±18.3 days, which was much shorter than the 71.7±14.4 days in the control group (P<0.001), and the length of ICU stay was much shorter in the study group than in the control group (P=0.005) (Table 4).
Table 4
| Characteristics | Control group | Study group | P value |
|---|---|---|---|
| Primary outcomes | |||
| 28-day mortality | 3 (2.8%) | 2 (2.4%) | 1.000 |
| Total mortality | 4 (3.7%) | 4 (4.9%) | 0.727 |
| Secondary outcomes | |||
| AKI | 32 (29.4%) | 13 (15.9%) | 0.029 |
| ARDS | 27 (24.8%) | 9 (11.0%) | 0.016 |
| Sepsis | 23 (21.1%) | 16 (19.5%) | 0.787 |
| Venous thromboembolism | 5 (4.6%) | 6 (6.1%) | 0.423 |
| Length of hospital stay | 71.7±14.4 | 59.3±18.3 | <0.001 |
| Length of ICU stay | 59.1±13.4 | 53.1±15.2 | 0.005 |
AKI, acute kidney injury; ARDS, acute respiratory distress syndrome.
Risk factors of AKI and ARDS were analyzed according to multivariable logistic regression (Table 5) and showed PCCO monitoring could significantly improve the incidence of AKI and ARDS in enrolled severe burns and TBSA was an important risk factor for both. In addition, the existence of inhalation injury and older age increased the incidence of ARDS after severe burns. The risk factors of length of hospital stay were then analyzed according to multivariable linear regression (Table 6) and identified PCCO monitoring as an important method to shorten the length of hospital stay (P=0.010). Higher TBSA and inhalation injury were related to longer hospital stay in enrolled patients, and the occurrence of burn-related complications, such as AKI, ARDS, and sepsis, prolonged the length of hospital stay.
Table 5
| Characteristics | Multivariable analysis | |
|---|---|---|
| OR (95% CI) | P value | |
| AKI | ||
| PCCO monitoring | 0.441 (0.192, 0.854) | 0.034 |
| TBSA | 1.104 (1.067, 1.143) | <0.001 |
| ARDS | ||
| PCCO monitoring | 0.383 (0.169, 0.871) | 0.022 |
| Older age | 1.009 (1.003, 1.015) | 0.034 |
| TBSA | 1.082 (1.046, 1.121) | <0.001 |
| Inhalation injury | 3.230 (1.349, 7.737) | 0.009 |
All collected characteristics were initially analyzed using univariable logistic regression analysis and any characteristic which showing significant effects on the incidence of burns-related complications was further analyzed using multivariable logistic regression. AKI, acute kidney injury; PCCO, pulse contour cardiac output; TBSA, total burn surface area.
Table 6
| Characteristics | Multivariable analysis | |
|---|---|---|
| β (95% CI) | P value | |
| PCCO monitoring | −4.333 (−7.630, −1.036) | 0.010 |
| TBSA | 0.454 (0.308, 0.601) | <0.001 |
| Inhalation injury | 3.310 (0.041, 6.580) | 0.047 |
| AKI | 6.997 (0.871, 13.123) | 0.025 |
| ARDS | 3.183 (0.753, 5.613) | 0.029 |
| Sepsis | 4.855 (1.501, 8.210) | 0.016 |
All collected characteristics were initially analyzed using univariable linear regression analysis and any characteristic which showing significant effects on the length of hospital stay was further analyzed using multivariable linear regression. PCCO, pulse contour cardiac output; TBSA, total burn surface area; AKI, acute kidney injury; ARDS, acute respiratory distress syndrome.
Discussion
Although PCCO monitoring technology has been proposed for more than one decade and has been applied in clinical patients for several years, there have been no relevant studies verifying its advantages compared with conventional monitoring. Our study was the first to verify the effect of PCCO monitoring on the prognosis of severe burns patients receiving fluid resuscitation, and the results showed that it effectively reduced the incidence of burns-related complications during the treatment and shortened the length of hospital stay. This study further confirmed the superiority and reliability of PCCO monitoring compared with traditional monitoring.
Nowadays, the mortality of severe burns patients worldwide is still at a relatively high level, and has been reported as ranging between 12.2% and 47.6% (3,21,22). As our burns center has many years of experience in severe burns diagnosis and treatment, the mortality is maintained at a relatively low level, and in this study, the overall mortality of enrolled patients was 3.7% in the control group and 4.9% in the study group, respectively. The overall mortality in all enrolled patients was 4.2%, and there was no significant difference in mortality between the two groups. This relatively low mortality also made it impossible to verify the impact of PCCO monitoring on the mortality of severe burns patients in this study. Previous studies have reported that risk factors associated with mortality included TBSA, body mass index, inhalation injury, and some serious complications (23-26). Considering the effects of PCCO monitoring on reducing burn-related complications of enrolled patients in this study, we proposed a hypothesis that it could also reduce mortality to a certain extent. However, this conclusion may need to be verified by more cases.
AKI and ARDS are the most common complications in the treatment of severe burns patients, their occurrence will significantly worsen the prognosis of patients, and our study showed that PCCO monitoring can effectively reduce their incidence. TBSA also acted as an important risk factor for AKI and ARDS. In previous studies, intra-abdominal hypertension, hypernatremia, and inhalation injury were risk factors for serious complications (27-29), while in the present study, inhalation injury was also found to be a risk factor for ARDS, but there was no significant relationship between it and AKI. Sepsis is also a common complication in severe burns patients, and we found its incidence to be 21.1% in the control group and 19.5% in the study group. Although the incidence was slightly lower in the study group, there was no significant difference between the two groups, which suggests that the occurrence of sepsis is not only related to rehydration, but also related to other risk factors. In addition, previous studies have shown that the occurrence of serious complications, such as sepsis, acute renal failure, ventilator use, and cardiac arrest, would significantly prolong the length of ICU stay and hospital stay of patients, which is consistent with the results of this study. PCCO monitoring has also been proven to shorten the length of hospital stay of patients according to multivariable linear regression.
By analyzing differences in the fluid volume index between the control group and study group, it was found that PCCO monitoring assisted liquid resuscitation could reduce the amount of liquid used, especially the amount of colloid. In the control group, excessive fluid administration may have led to the accumulation of fluid in the organs, resulting in organ edema, increased intra-abdominal pressure, and hindered pulmonary gas exchange, increasing the incidence of serious burns-related complications. This also suggests there may be excessive fluid administration in previous treatment, which needs to be corrected.
It should be noted that there were some limitations in this study. Firstly, we did not collect patient output data, which would have provided a deeper understanding of the whole treatment state and more information data of the effect of PCCO monitoring on the prognosis of severe burns patients. Secondly, the baseline data of the control group and study group were not well matched, and although multivariable logical regression and linear regression were used for adjustment, there may still be some bias in the results. Thirdly, this study was a retrospective cohort study, which inevitably carries some data deviations, and can be improved by a prospective study in the future. Fourthly, other treatments, such as infection control, nutritional support and scar repair, may also affect the prognosis of severe burn patients, which need more detailed study in the future.
Conclusions
Based on the results from this retrospective study, PCCO monitoring can be used as an effective auxiliary measure for fluid resuscitation in severely burned patients, which can effectively reduce the occurrence of some serious complications, such as AKI and ARDS, and shorten the length of hospital and ICU stay. Although the number of cases in this study is relatively small, the results provide some evidence for the use of PCCO monitoring in burns patients and can be further investigated in future studies.
Acknowledgments
Funding: None.
Footnote
Reporting Checklist: The authors have completed the STROBE reporting checklist. Available at https://dx.doi.org/10.21037/apm-21-2587
Data Sharing Statement: Available at https://dx.doi.org/10.21037/apm-21-2587
Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://dx.doi.org/10.21037/apm-21-2587). The authors have no conflicts of interest to declare.
Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. All procedures performed in this study involving human participants were in accordance with the Declaration of Helsinki (as revised in 2013). The study was approved by institutional ethics committee of Affiliated Hospital of Jiangnan University (No. 2021011). Individual consent for this retrospective analysis was waived.
Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.
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(English Language Editor: B. Draper)
