Effect Of Goal-Directed Haemodynamic Therapy On Short-Term Postoperative Complications In Patients With Extensive Burns: A Single-Centre Randomised Controlled Trial

doi:10.21203/rs.3.rs-1341626/v1

Download PDF

Research Article

Effect Of Goal-Directed Haemodynamic Therapy On Short-Term Postoperative Complications In Patients With Extensive Burns: A Single-Centre Randomised Controlled Trial

https://doi.org/10.21203/rs.3.rs-1341626/v1

This work is licensed under a CC BY 4.0 License

Version 1

posted

You are reading this latest preprint version

Background: To investigate the effect of goal-directed hemodynamic treatment on perfusion and short-term prognosis in patients undergoing early Tangential excision and skin grafting for extensive burns.

Methods: Ninety-five patients with extensive burns undergoing early Tangential excision and skin grafting were randomly divided into a standard hemodynamic management group (control group) and a goal-directed therapy group (GDHT group), with the control group guided by conventional parameters and the GDHT group guided by stroke volume (SV) based on Vigileo. The primary outcomes were cardiac complications, pulmonary complications, neurological disease, acute kidney injury, and pain within 7 days postoperatively. Secondary outcomes included microcirculatory perfusion metrics: The central venous-arterial carbon dioxide partial pressure difference (Pcv-aCO2), and blood lactate (Lac). investigators assessing outcomes were blinded to group allocation.

Results: When analysing 47 subjects in the GDHT group and 48 subjects in the control group, fewer patients in the GDHT group had postoperative pulmonary complications [pneumonia (2:9, P=0.027); oxygenation index <300 (3:8, P=0.041)] and controls were more likely to have atrial fibrillation (4:12, P=0.032) Renal and neurological complications did not differ between groups. Pcv-aCO2 and Lac were higher in the Con group after the intervention compared to the control group, and there was no difference between the two groups postoperatively. In this study, Pcv-aCO2 and Lac were Key influencing factors for pulmonary complications within 7 days postoperatively (Beta=0.197, P=0.000; Beta=0.147, P=0.000).

Conclusion: SV-guided GDHT improves microcirculatory perfusion and has fewer short-term postoperative complications compared with standard hemodynamic therapy.

Trial registration: NCT05221788 (03/02/2022)

Goal-directed hemodynamic treatment

Extensive burn

Tissue perfusion；Short term prognosis

Early excision of dead/necrotic tissue and temporary or permanent coverage of the open area reduces the chance of wound infection and systemic sepsis and has been widely used clinically in the field of burns. Patients are often brought to the operating room in the early stages of burns when they are experiencing significant fluid transfer, resuscitation of large volumes of fluid during the shock phase, creating a positive fluid balance, recovery of capillary permeability into the resorption phase, and reabsorption of excess fluid from the tissue interstitium into the circulation, which can result in volume overload leading to pulmonary oedema and Acute Respiratory Distress Syndrome (ARDS) if the positive fluid balance strategy is continued intraoperatively [1]. Restrictive fluid administration is also controversial, with a large meta-analysis showing that restrictive fluid rehydration does not improve unimpeded survival in patients undergoing major abdominal surgery for up to one year postoperatively, but rather increases the incidence of perioperative acute kidney injury [2]. A perioperative fluid therapy approach that optimises intravascular volume, improves tissue oxygen transport, and prevents complications from excessive intraoperative fluid should be sought in patients undergoing early scab grafting for major burns.

Goal-Directed Heamodynamic Therapy (GDHT) is the real-time modulation of the patient's haemodynamic and oxygen dynamic status based on a number of well-correlated volume haemodynamic parameters, with the goal of balancing the oxygen supply and demand in the patient's tissue cells, providing an effective guide to volume management in major surgical anaesthesia, and has been used as a preventive measure to avoid organ failure in perioperative and critical care medicine, and its feasibility has been demonstrated in a variety of surgical procedures [3]. However, the effects of GDHT on outcomes after various types of surgery are conflicting [4, 5]. We therefore conducted a randomised controlled study in patients undergoing early debridement and implantation of extensive burns to observe the effect of stroke volume (SV) guided intraoperative haemodynamic management on patient perfusion and short-term prognosis.

This study was reviewed and approved by ethics committee (full name of the committee: Guangzhou Red Cross Hospital Ethics Committee; reference No.2020-079-02). Study protocol was registered in the Clinical trail.gov PRS prior to patient enrollment (Registration no. NCT05221788, Principal investigator: Dr. Bing Liang, Date of registration: 03/02/2022). Informed consent was obtained from all patients before enrollment. The authors assert that all procedures contributing to this work comply with the ethical standards of the relevant national and institutional committees on human experimentation and with the Helsinki Declaration of 1975, as revised in 2008.

This study used PASS11 to estimate the sample size. The results found that a minimum of 94 patients needed to be included and a 5% lost to follow-up rate was considered, with 100 patients included in the study.

Patients with extensive burns were screened according to the following inclusion criteria: (i) Age between 18 and 65 years, (ii) Burn area ≥ 50% Total Body Surface Area (TBSA) or third-degree burns area ≥ 20% TBSA, (iii)Patients undergoing first surgery after fluid resuscitation (having passed the shock phase). Types of surgery include incisional decompression, scalpel implantation, etc. Patients with severe heart or lung disease prior to the burn injury and combined with severe internal organ damage would be excluded.

Patients, anaesthetists and surgeons were unaware of the random allocation. The full anaesthetic procedure, experimental grouping, intervention protocol, experimental data recording and processing were carried out by clinicians with no knowledge of the overall experimental design. Patients were randomised 1:1 into GDHT group and Con group according to a random number table, without stratification. Random allocation was done in sequentially numbered opaque envelopes. Patients were unaware of the grouping and clinicians in charge of the intraoperative treatment protocol in both groups was only aware of the specific protocol and was unaware of the grouping and the purpose of the experiment. All results were processed by a researcher who was unaware of the patient grouping.

All patients were routinely monitored for Non-Invasive Blood Pressure (NIBP), ECG, SpO2 and Bispectral Index (BIS) on entry to the operating room, with vein intubation connected to a Braun sensor for continuous monitoring of central venous pressure (CVP) and arterial intubation connected to a FloTrac™ sensor (Edwards Lifesciences, USA) and a Vigileo monitoring system for continuous monitoring of invasive blood pressure (IBP), SV, cardiac output (CO), and cardiac index (CI). All patients were given etomidate 0.2-0.3mg/kg, sufentanil 0.2-0.4ug/kg and cis-atracurium 0.1-0,2m/kg intravenously without preoperative medication, and were mechanically ventilated after tracheal intubation or tracheotomy tube with tidal volume 6-8ml/kg, respiratory rate10-14 times/min, maintaining PETCO2 35-45mmHg. Intraoperatively, propofol, remifentanil and cis-atracurium were pumped continuously to maintain BIS at 40–60. nasopharyngeal temperature was maintained above 36°C by infusion of warmed fluids and warmers. All patients were taken to the burn ICU after surgery.

①GDHT group: Give 3ml/kg/h of compound sodium lactate intravenously as a basal rehydration volume before induction and 200ml of electrolyte solution after induction of anaesthesia. If SV increases ≥ 10%, continue to give 200ml of electrolyte solution until SV increases < 10%. After the fluid challenge, if SV increases < 10% but mean arterial pressure (MAP) < 65 mmHg and/or CI < 2.5L/min/m², give low dose norepinephrine continuous pumping and/or dobutamine continuous pumping. If hypotension is associated with hypovolemia (defined as Urine Output (UO) < 0.5ml/kg/h and/or heart rate (HR) more than 20% above baseline), plasma is administered until UO and/or HR return to normal. Fluid responsiveness and haemodynamic variables were reassessed at least every 15 minutes, and more frequently in cases of haemodynamic instability (as shown in Fig. 1).

②Con group: Continuous infusion of compounded sodium lactate 5–7 ml/kg/h, colloidal solution (succinyl gelatin injection, Braun Pharmaceuticals GmbH, Germany), norepinephrine and dobutamine were allowed at the discretion of the anaesthetist. Intraoperative treatment goals in the control group were flexible in order to avoid the two extremes of clinical practice and practice bias.

In both groups, if Hb < 80 g/L, concentrated red blood cells were transfused according to body weight until Hb ≥ 80 g/L.

The primary outcomes included new atrial fibrillation within 7 days of surgery; clinically relevant episodes of hypotension (MAP drop ≥ 20% and requiring vasoactive medication for more than 10 min); pulmonary complications (pneumonia, pulmonary oedema, pleural effusion, oxygenation index < 300); neurological disorders (stroke and delusions); acute kidney injury (as defined by the criteria for acute kidney injury); and pain. And secondary outcomes included Lac, Pcv-aCO2 reflecting microcirculatory perfusion (preoperative: T1, intraoperative 1 hour: T2, intraoperative 2 hours: T3, postoperative: T4, postoperative 24 hours: T5, postoperative 7 days).

Statistical analysis

Data from 95 patients were collected during the study period and SPSS 25.0 and GraphPad Prism 9.0 software were adopted for statistical analysis. All results are expressed as mean (standard deviation) or median (interquartile range) unless otherwise stated. Differences in perioperative continuous variables between the GDHT and Con groups were compared using the Student’s t-test, and categorical variables were compared using the chi-square test. Correlations between tissue perfusion parameters and postoperative complications were tested using binary regression. A P value < 0.05 was considered statistically significant.

This study was conducted in Guangzhou Red Cross Hospital, Guangzhou, China, from January 2020 to December 2021. The CONSORT flow diagram is showed in Fig. 2. 100 patients were enrolled in the trial, 95 patients were randomly assigned to either group, of the 5 excluded from the study, 2 patients declined to participate and 3 were excluded due to blood supply constraints to maintain a haemoglobin ≥ 80 g/L.

Patients’ baseline and surgical characteristics in both groups is shown in Table 1. UO was higher in the GDHT group compared to the Con group on the day of surgery (219 ± 66.6 vs 193 ± 50.0, P = 0.034). There were no significant differences in burn area, preoperative comorbidities, ASA, NYHA, intraoperative time, total fluids administered and blood loss. We also observed no difference in the amount of fluids administered to patients in BICU. The GDHT group was treated with more positive inotropic medication (p < 0.05).

Table 1

Baseline and surgical characteristics
	GDHT n = 47		P-valve
male (%)	26(55.3%)	25(52.1%)	0.752
Age (y)	39.8 ± 13.2	41.6 ± 14.1	0.522
BMI (kg/m²)	21.6 ± 2.4	20.6 ± 2.9	0.071
Burn area (%)	70.1.±12.1	68.6 ± 13.8	0.575
Complications
Electrolyte disorder, n (%)	29(61.70%)	26(54.2%)	0.228
Pulmonary infection, n (%)	4(8.51%)	6(12.5%)	0.765
Renal dysfunction (%)	9(19.1%)	7(14.6%)	0.552
Arrhythmia (%)	7(14.9%)	10(20.8%)	0.450
ASA	II(22)/III༈25༉	II(27)/III༈21༉	0.357
NYHA	II(38)/III༈9༉	II(34)/III༈14༉	0.254
Operation time (h)	4.1 ± 0.9	3.9 ± 0.7	0.229
Fluid (ml) Intraoperative	1142 ± 171	1091 ± 163	0.148
UO (ml)	219 ± 66.6	193 ± 50.0	0.034
Blood loss (ml)	345 ± 78	371 ± 62	0.075
Fluid (ml) Postoperative	2512 ± 266	2602 ± 301	0.126
Norepinephrine(mg)	0.04 ± 0.01	0.06 ± 0.02	0.000
dobutamine(n)	12(25.5%)	6(12.5%)	0.105
BMI, body mass index; ASA, American Society of Anesthesiologists; NYHA, New York Hospital Association; UO, urine output

The perioperative haemodynamic changes in both groups are showed in Table 2. There were no differences in the indicators between the two groups at T1 and T5, while the GDHT group had higher SV, MAP and CI than the Con group during anaesthesia and surgery (T2, T3 and T4), while there were no differences in HR and CVP.

Table 2

The perioperative haemodynamic changes
	MAP	HR	SV	CI	CVP
T1
GDHT	71 ± 15	63 ± 9	64 ± 10	3.0 ± 0.5	8.5 ± 1.7
Con	71 ± 11	62 ± 8	62 ± 9	3.1 ± 0.6	8.3 ± 1.8
T2
GDHT	82 ± 12*	63 ± 9	73 ± 11*	4.0 ± 0.6*	11.2 ± 2.1
Con	73 ± 12*	64 ± 8	61 ± 7*	3.2 ± 0.6*	10.9 ± 2.2
T3
GDHT	85 ± 12*	63 ± 8	70 ± 9*	4.3 ± 0.5*	10.8 ± 2.4
Con	75 ± 9*	66 ± 9	63 ± 7*	3.1 ± 0.4*	10.6 ± 2.3
T4
GDHT	86 ± 9*	64 ± 8	69 ± 7*	3.8 ± 0.5*	11.1 ± 1.9
Con	74 ± 8*	66 ± 9	62 ± 6*	3.2 ± 0.7*	10.8 ± 2.1
T5
GDHT	70 ± 10	66 ± 12	61 ± 18	3.2 ± 0.4	8.8 ± 1.9
Con	71 ± 9	65 ± 15	60 ± 17	3.1 ± 0.5	8.5 ± 1.8
*A p value < 0.05 was considered statistically significant between groups at the same point.

The incidence of complications is shown in Table 3. In the GDHT group, the incidence of most complications was slightly lower than in the Con group, with the Con group being more likely to have respiratory complications and new-onset atrial fibrillation within 7 days postoperatively than the GDHT group (p<0.05).

Table 3

The incidence of complications within 7 days postoperatively
Complications		GDHT group N = 47	Con group N = 48	P values
	New onset atrial fibrillation	n = 4(8.5%)	n = 12(25.0%)	0.032
	hypotensive episodes	n = 5(10.6%)	n = 9(18.8%)	0.265
Neurological	Strokes	n = 0(0.0%)	n = 1(2.1%)	1.000
	Delirium	n = 3(6.4%)	n = 2(4.2%)	0.981
Pulmonary	Pneumonia	n = 2(4.3%)	n = 9(18.8%)	0.027
	Pleural effusion	n = 4(8.5%)	n = 9(18.8%)	0.232
	Oxygen Index༜300	n = 6(12.8%)	n = 15(31.3%)	0.030
Renal	Acute kidney injury	n = 1(2.1%)	n = 0(0.0%)	1.000
Pain	Postoperative pain	n = 4(8.5%)	n = 6(12.5%)	0.765

Table 4 depicts the changes in perfusion indicators in the perioperative period between the two groups. There were no differences in the indicators between the two groups at T1, T2 and 7 days postoperatively, while the central venous-to-arterial carbon dioxide partial pressure difference (Pcv-aCO2) was lower in the GDHT group than in the Con group at time points T3, T4 and T5, and blood lactate (Lac) was higher in both groups.

Table 4

Changes in perfusion indicators in the perioperative period
Group	Time point	Pcv-aCO2(mmol/L)
GDHT group	Preoperative	4.12 ± 1.08	1.12 ± 0.54	342 ± 38
n = 47	T1	4.75 ± 0.92	1.35 ± 0.40	339 ± 41
n = 47	T2	6.35 ± 1.17	1.36 ± 0.53	357 ± 44*
	T3	6.13 ± 1.42*	1.55 ± 0.64	349 ± 41*
	T4	5.95 ± 1.71*	1.65 ± 0.48*	351 ± 39*
	T5	5.35 ± 1.32*	1.65 ± 0.83*	356 ± 44*
	7d postoperative	4.54 ± 1.22	1.38 ± 0.61	338 ± 47*
Con group	Preoperative	4.41 ± 1.22	1.08 ± 0.55	333 ± 39
n = 48	T1	5.35 ± 1.45	1.15 ± 0.45	336 ± 41
n = 48	T2	6.55 ± 2.27	1.26 ± 0.54	323 ± 32
	T3	7.42 ± 1.52	1.76 ± 0.71	321 ± 39
	T4	8.34 ± 2.28	2.35 ± 0.82	316 ± 38
	T5	8.60 ± 1.79	2.55 ± 0.62	319 ± 33
	7d postoperative	4.71 ± 1.39	1.45 ± 0.61	312 ± 38
*A p value < 0.05 was considered statistically significant compared with Con Group at the same point.

To observe whether perfusion indicators during GDHT had predictive value for complications, as shown in Table 5, we performed time-weighted perfusion indicators (Pcv-aCO2, Lac) during GDHT (T2-T4), plus conventional hemodynamic parameters, and binary logistic regression analysis with respiratory complications that differed between groups within 7 days postoperatively as the dependent variable, to identify independent influences on the occurrence of perioperative pulmonary complications in patients with severe burns. The results showed that Pcv-aCO2, Lac, and CI were associated with respiratory complications within 7 days postoperatively, where the degree of influence was from highest to lowest such as: Pcv-aCO2, Lac, CI.

Table 5 Binary logistic stepwise regression analysis with respiratory complications at 7d as the dependent variable

In	Variable	Standard coefficient	ods ratio	t-value	Prob. level
Yes	Pcv-aCO2	0.213	0.18	-4.001	0.000
Yes	Lac	0.165	0.472	-25.73	0.000
No	ScvO2	-
No	MAP	-
No	HR	-
Yes	CI	0.056	0.041	2.375	0.016
No	SV	-
No	CVP	-

Early application of haemodynamic monitoring and use of haemodynamic indicators as a guide to maintain perioperative SV through fluid loading, thus minimising organ damage associated with inadequate oxygen supply. Fluids and medications are adjusted in a timely manner to avoid organ underperfusion and fluid overload [6–7]. Numerous trials and meta-analyses have shown that GDHT reduces postoperative complications and mortality in high-risk surgical patients, regardless of the choice of monitoring method or target variable [8–9]. Severely burned patients undergoing scab grafting, although most have passed the most dangerous shock phase into infection, are still physiologically unstable and may return to shock at any time, falling within the category of high-risk surgical patients, and previous studies of GDHT in high-risk surgical patients have not included severely burned patients. Furthermore, a recent meta-analysis and several trials suggest that the benefits of GDHT may not be as pronounced as previously thought [10], so the question of whether GDHT improves postoperative outcomes is unclear.

In this randomised trial on the effect of GDHT guided by FloTrac®-Vigileo® on postoperative complications in patients with extensive burns undergoing early scab grafting, subjects in the GDHT group had a lower incidence of complication than patients in the control group treated as usual. The GDHT group had a lower incidence of respiratory complications as well as new-onset atrial fibrillation within 7 days postoperatively compared to the control group, with no differences in subjects' basic and surgical characteristics or postoperative pain relief. As for secondary outcomes, similar to previous studies, GDHT had an effect on improving tissue perfusion [11], with no differences in perfusion indicators between the two groups at T1, T2 and 7 days postoperatively. Pcv-aCO2 and Lac at T3, T4 and T5 were superior to the Con group. A study by Aaen et al. showed that goal-directed fluid therapy close to the maximum SV (GDHT group) did not improve prognosis after surgery for intestinal obstruction or gastrointestinal perforation and may prolong the length of hospital stay [12]. This suggests that the benefits of GDHT lie not only in providing additional fluid when needed, but also in directing and responding to fluid use and in avoiding unnecessary fluid delivery when achieving haemodynamic goals.

In our study, similar to other studies [13–14], we found no difference in intraoperative or postoperative fluid, and similarly, we found no difference in MAP or HR. Therefore, the beneficial effect of GDHT may be due to the administration of fluids at the correct time, avoiding hypovolemia and hypoperfusion. Unlike other studies [15], we did not use supernormal CI values as a target, but relied on SV optimisation, whose values were not CI-dependent and influenced by HR. We also monitored oxygen supply and perfusion indicators and found that optimising intravascular volume and improving tissue perfusion and oxygenation may be due to the fact that GDHT ensures visceral circulation and reduces the systemic inflammatory response following surgical trauma. A previous study [13] in which 108 subjects undergoing colorectal resection were randomised to an intraoperative GDHT group and a standard fluid therapy group (3640 ml VS 3830 ml) showed that GDHT reduced interleukin levels. The results in the GDHT group can be attributed to timing, not only to avoid tissue ischaemia, but also to avoid infusion of fluids at inappropriate times. Giving too much fluid at the wrong time may lead to fluid overload, damaging the endothelial glycocalyx and leading to oedema and postoperative complications [16]. Although Pestana and his colleagues could not show different outcomes in patients with colorectal disease [17], a meta-analysis showed that the combination of GDHT and positive inotropic drugs to optimise CI yielded better outcomes than GDHT alone [18]. In our study, the GDHT group had a higher CI and a better oxygenation index than Con group, and optimising cardiac function in the absence of fluid overload may improve oxygenation. subjects in the GDHT group had lower doses of vasopressors, but were treated more frequently with positive inotropic drugs, after increasing the volume per beat and CI, thus improving lung perfusion. We speculate that this may reduce the incidence of pulmonary complications. The GDHT group had a lower incidence of new-onset atrial fibrillation and pulmonary oedema than the Con group, a < 10% increase in SV after fluid infusion and the use of positive inotropic drugs to avoid low CO and thus optimise organ perfusion without the risk of volume overload. This is particularly important in the perioperative period of early surgery in patients with extensive burns, when fluid overload can be harmful. At this point the patient goes through the shock phase and enters the resorption phase, capillary permeability returns and excess fluid from the tissue interstitium is reabsorbed into the circulation, leading to pulmonary oedema and ARDS if the volume load is excessive [19].

Although there were differences in drug use between the two groups, the volume of infusion was comparable between the groups. The timing of volume optimisation may be critical. Fluids in the Con group may have been given when the CI was still adequate, whereas in the GDHT group they were given when there was room for optimization of SV. If traditional parameters suggestive of hypovolemia (e.g. HR, hypotension, UO) are used to decide whether to start fluid therapy, there may be a delay in rehydration, as the actual hypovolemic state due to reduced SV and CI may have been present for some time. Overall, the choice of timing of perioperative fluid therapy may be more important than the choice of methodology, and early GDHT can be of great importance in preventing the development and occurrence of adverse pathophysiological processes.

We selected Pcv-aCO2 and Lac as indicators of microcirculatory perfusion because of their particular value in septic patients for reflecting early resuscitation success [20–21], and the pathophysiological status of patients with severe burns is similar to that of septic patients. Previous studies have shown that in trauma patients, early lactate values are strongly associated with prognosis [22–23], and after major abdominal surgery, increased lactate values are associated with postoperative complications [24]. In our study, lactate levels were similar in both groups preoperatively and early in surgery and seven days postoperatively, and lactate was superior in the GDHT group than in the Con group after fluid therapy. Lactate was a significant influence on pulmonary complications at 7 days postoperatively (Beta = 0.165, P = 0.000), which is consistent with previous studies.

Pcv-aCO2 indicates whether the body has sufficient blood flow to flush the CO2 produced by the tissues, and the amount of CO2 removed by the body per unit time (VCO2) is: VCO2 = K × CO × Pcv-aCO2 [25]. That is, Pcv-aCO2 is proportional to total CO2 content and inversely proportional to CO, but the subject of this study was in the pathophysiological conditions of burn shock, where absolute or relative insufficiency of circulating blood volume coexists with microcirculatory disorders, and although the infusion volumes of the two groups were comparable, the GDHT group was given more positive inotropic drugs to optimize cardiac function, CO rose, blood flow increased, CO2 clearance was faster, and Pcv-aCO2 decreased. Fluid therapy at different time windows of treatment directly influences the outcome of Pcv-aCO2 [26]. If coexisting CO levels are low, it is inferred that the lack of total blood flow leads to an increase in Pcv-aCO2 and resuscitation measures should focus on volume replacement and strengthening of cardiac function. Robin et al [27] demonstrated that elevated Pcv-aCO2 at ICU admission was associated with postoperative complications. However, a retrospective study by Pierre et al [28] concluded that Pcv-aCO2 did not predict the prognosis of patients after cardiac surgery. In this study, Pcv-aCO2 was a significant influence on pulmonary complications within 7 days postoperatively (Beta = 0.213, P = 0.000).

There are several limitations to this study. Firstly, it does not overcome an important shortcoming of current goal-directed therapy, which consist of small, single-centre studies that focus on minor complications as an outcome measure. We expect that future multi-centre, large clinical trials will be conducted to further validate the findings. Second, clinical heterogeneity may have compromised the effectiveness of GDHT treatment, and despite the fact that the preoperative data of the two groups were not statistically different and the inclusion of patients was restricted to elective, high-risk burn surgery, heterogeneity could not be avoided. Thirdly, because of the small number of patients with severe burns, we did not strictly specify that all procedures be performed by the same treatment group, and the operation of different treatment groups may also have influenced the results. Finally, the short postoperative observation period of seven days does not provide a good indication of long-term outcomes, but severe burns patients often require multiple procedures, which is one of the reasons we chose a seven-day observation window.

In summary, GDHT of maximising SV improves microcirculatory perfusion in patients undergoing early surgery for extensive burns and is associated with a reduction in short-term postoperative complications, with the expectation that more medical centres and more patients will be available to validate our results in the future.

GDHT: Goal-Directed Haemodynamic Therapy

ARDS: Acute Respiratory Distress Syndrome

SV: Stroke Volume

TBSA: Total body Surface Area

NIBP: Non-Invasive Blood Pressure

IBP: Invasive Blood Pressure\

CVP: Central Venous Pressure

CO: Cardiac Output

CI: Cardiac Index

MAP: Mean Arterial Pressure

HR: Heart Rate

UO: Urine Output

Pcv-aCO2: The central venous-arterial carbon dioxide partial pressure difference

Lac: Blood Lactate

Ethics approval and consent to participate

This study was reviewed and approved by Guangzhou Red Cross Hospital Ethics Committee of Registering Clinical Trails (Reference No. 2020-079-02). Study protocol was registered in the Clinical Trial.gov PRS prior to patient enrollment (Registration no. NCT05221788, Principal investigator: Dr. Bing Liang, Date of registration: 03/02/2022). Informed consent was obtained from all patients before enrollment. All the methods were performed in accordance with the relevant guidelines and regulations (Declaration of Helsinki).

Consent for publication

Not applicable.

Availability of data and materials

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

Competing interests

None of the authors declare any competing interests.

Funding

Dr. Bing Liang received funding support from Guangzhou Science and Technology Program Project Fund (No. 202103000022) and Guangdong Medical Science and Technology Research Fund (No. A2021106)

Author’s contributions

Jianhao Zeng and Haoran Huang helped in patients’ recruitment, data collection, data analysis and drafting the manuscript. Weilong Peng, Lianjie Cai and Yan Zhang helped in data collection. Bing Liang and Yang Cao designed this study, analyzed data and wrote the manuscript. The authors read and approved the final manuscript.

Acknowledgements

The authors would like to thank all the staff in our operation room for their generous support during this study.

Authors information

Bing Liang, Guangzhou Red Cross Hospital, Department of Anesthesiology, The Fourth Affiliated Hospital of Jinan University School of Medicine, 510220, Email：[email protected]

Lianjie Cai, Guangzhou Red Cross Hospital, Department of Anesthesiology, The Fourth Affiliated Hospital of Jinan University School of Medicine, 510220, Email：[email protected]

Haoran Huang, Guangzhou Red Cross Hospital, Department of Anesthesiology, The Fourth Affiliated Hospital of Jinan University School of Medicine, 510220, Email： [email protected]

Jianhao Zeng, Guangzhou Red Cross Hospital, Department of Anesthesiology, The Fourth Affiliated Hospital of Jinan University School of Medicine, 510220, Email： [email protected]

Weilong Peng, Guangzhou Red Cross Hospital, Department of Anesthesiology, The Fourth Affiliated Hospital of Jinan University School of Medicine, 510220, Email： [email protected]

Yan Zhang, Guangzhou Red Cross Hospital, Department of Anesthesiology, The Fourth Affiliated Hospital of Jinan University School of Medicine, 510220, Email： [email protected]

Yang Cao, Guangzhou Red Cross Hospital, Department of Anesthesiology, The Fourth Affiliated Hospital of Jinan University School of Medicine, 510220, Email：[email protected]

[1] Bittner EA, Shank E, Woodson L, Martyn JA. Acute and perioperative care of the burn-injured patient. Anesthesiology. 2015;122(2):448-464. doi:10.1097/ALN.0000000000000559.

[2] Myles PS, Bellomo R, Corcoran T, et al. Restrictive versus Liberal Fluid Therapy for Major Abdominal Surgery. N Engl J Med. 2018;378(24):2263-2274. doi:10.1056/NEJMoa1801601

[3] Landais A, Morel M, Goldstein J, Loriau J, Fresnel A, Chevalier C, et al. Evaluation of financial burdens following complications after major surgery in France: potential returns after perioperative goal directed therapy.

Anaesth Crit Care Pain Med. 2017;36:151–5.

[4] Akira Mukai, Koichi Suehiro, Ryota Watanabe, Takashi Juri, et al. Impact of intraoperative goal-directed fluid therapy on major morbidity and mortality after transthoracic oesophagectomy: a multicentre, randomised controlled trial. British Journal of Anaesthesia, doi: 10.1016/j.bja.2020.08.060.

[5] E. Bartha, C. Arfwedson, A. Imnell, M. E. Fernlund, L. E. Andersson and S. Kalman.Randomized controlled trial of goal-directed haemodynamic treatment in patients with proximal femoral fracture. British Journal of Anaesthesia 110 (4): 545–53 (2013).doi:10.1093/bja/aes468.

[6] Saugel B, Michard F, Scheeren TWL. Goal-directed therapy: hit early and personalize!. J Clin Monit Comput. 2018;32(3):375-377. doi:10.1007/s10877-017-0043-x

[7] Fellahi JL, Futier E, Vaisse C, et al. Perioperative hemodynamic optimization: from guidelines to implementation-an experts' opinion paper. Ann Intensive Care. 2021;11(1):58. Published 2021 Apr 14. doi:10.1186/s13613-021-00845-1

[8] Mukai A, Suehiro K, Watanabe R, et al. Impact of intraoperative goal-directed fluid therapy on major morbidity and mortality after transthoracic oesophagectomy: a multicentre, randomised controlled trial. Br J Anaesth. 2020;125(6):953-961. doi:10.1016/j.bja.2020.08.060

[9] Dushianthan A, Knight M, Russell P, Grocott MP. Goal-directed haemodynamic therapy (GDHT) in surgical patients: systematic review and meta-analysis of the impact of GDHT on post-operative pulmonary complications. Perioper Med (Lond). 2020;9:30. Published 2020 Oct 15. doi:10.1186/s13741-020-00161-5

[10] Wongtangman K, Wilartratsami S, Hemtanon N, Tiviraj S, Raksakietisak M. Goal-Directed Fluid Therapy Based on Pulse-Pressure Variation Compared with Standard Fluid Therapy in Patients Undergoing Complex Spine Surgery: A Randomized Controlled Trial [published online ahead of print, 2021 May 11]. Asian Spine J. 2021;10.31616/asj.2020.0597. doi:10.31616/asj.2020.0597

[11] Messina A, Robba C, Calabrò L, et al. Association between perioperative fluid administration and postoperative outcomes: a 20-year systematic review and a meta-analysis of randomized goal-directed trials in major visceral/noncardiac surgery. Crit Care. 2021;25(1):43. Published 2021 Feb 1. doi:10.1186/s13054-021-03464-1

[12] Aaen AA, Voldby AW, Storm N, et al. Goal-directed fluid therapy in emergency abdominal surgery: a randomised multicentre trial. Br J Anaesth. 2021;127(4):521-531. doi:10.1016/j.bja.2021.06.031

[13] Noblett SE, Snowden CP, Shenton BK, Horgan AF. Randomized clinical trial assessing the effect of Doppler-optimized fluid management on outcome after elective colorectal resection. Br J Surg. 2006;93(9):1069-1076. doi:10.1002/bjs.5454

[14] Salzwedel C, Puig J, Carstens A, et al. Perioperative goal-directed hemodynamic therapy based on radial arterial pulse pressure variation and continuous cardiac index trending reduces postoperative complications after major abdominal surgery: a multi-center, prospective, randomized study. Crit Care. 2013;17(5):R191. Published 2013 Sep 8. doi:10.1186/cc12885

[15] de Waal EEC, Frank M, Scheeren TWL, et al. Perioperative goal-directed therapy in high-risk abdominal surgery. A multicenter randomized controlled superiority trial. J Clin Anesth. 2021;75:110506. doi:10.1016/j.jclinane.2021.110506

[16] Ripollés-Melchor J, Chappell D, Espinosa Á, et al. Perioperative fluid therapy recommendations for major abdominal surgery. Via RICA recommendations revisited. Part I: Physiological background [published correction appears in Rev Esp Anestesiol Reanim. 2017 Aug - Sep;64(7):423].

[17] Pestaña D, Espinosa E, Eden A, et al. Perioperative goal-directed hemodynamic optimization using noninvasive cardiac output monitoring in major abdominal surgery: a prospective, randomized, multicenter, pragmatic trial: POEMAS Study (PeriOperative goal-directed thErapy in Major Abdominal Surgery). Anesth Analg. 2014;119(3):579-587. doi:10.1213/ANE.0000000000000295

[18] Hamilton MA, Cecconi M, Rhodes A. A systematic review and meta-analysis on the use of preemptive hemodynamic intervention to improve postoperative outcomes in moderate and high-risk surgical patients. Anesth Analg. 2011;112(6):1392-1402. doi:10.1213/ANE.0b013e3181eeaae5

[19] Tam N Pham 1, Leopoldo C Cancio, Nicole S Gibran, American Burn Association.American Burn Association practice guidelines burn shock resuscitation. J Burn Care Res. Jan-Feb 2008;29(1):257-66.

doi: 10.1097/BCR.0b013e31815f3876.

[20] Vallée F, Vallet B, Mathe O, et al. Central venous-to-arterial carbon dioxide difference: an additional target for goal-directed therapy in septic shock?. Intensive Care Med. 2008;34(12):2218-2225. doi:10.1007/s00134-008-1199-0

[21] Jones AE, Shapiro NI, Trzeciak S, et al. Lactate clearance vs central venous oxygen saturation as goals of early sepsis therapy: a randomized clinical trial. JAMA. 2010;303(8):739-746. doi:10.1001/jama.2010.158

[22] Nguyen HB，Rivers EP，Knoblich BP，et al. Early lactate clearance is associated with improved outcome in severe sepsis and septic shock［J］. Crit Care Med，2004，32（8）：1637-1642.

[23] Marie-Alix Régnier 1, Mathieu Raux, Yannick Le Manach,et al, Prognostic significance of blood lactate and lactate clearance in trauma patients.Anesthesiology. 2012Dec;117(6):127688. doi:10.1097/ALN.0b013e318273349d.

[24] C K Lausch, A Lorch, S Giertzuch, A Rieger, et al. Prognostic relevance of pre- and postoperative plasma l-lactate measurements in calves with acute abdominal emergencies. J Dairy Sci.2020 Feb;103(2):1856-1865.

doi: 10.3168/jds.2019-17224. Epub 2019 Nov 20.

[25] Giovannini I,Chiarla C,Boldrini G,et al.Calculation of venoarterial CO₂ concentration difference [J].J Appl Physiol (1985),1993,74(2):959-964.DOI:10.1152/jappl.1993.74.2.959.

[26] Mouncey PR, Osborn TM, Power GS, et al. Trial of early, goal-directed resuscitation for septic shock. N Engl J Med. 2015;372(14):1301-1311. doi:10.1056/NEJMoa1500896

[27] Robin E, Futier E, Pires O, et al. Central venous-to-arterial carbon dioxide difference as a prognostic tool in high-risk surgical patients. Crit Care. 2015;19(1):227. Published 2015 May 13. doi:10.1186/s13054-015-0917-6

[28] Huette P, Beyls C, Mallat J, et al. Central venous-to-arterial CO2 difference is a poor tool to predict adverse outcomes after cardiac surgery: a retrospective study. La différence entre le CO2 veineux central et artériel est un outil médiocre pour prédire les devenirs défavorables après une chirurgie cardiaque : une étude rétrospective. Can J Anaesth. 2021;68(4):467-476. doi:10.1007/s12630-020-01881-4

No competing interests reported.

Download PDF

Version 1

posted

You are reading this latest preprint version

Effect Of Goal-Directed Haemodynamic Therapy On Short-Term Postoperative Complications In Patients With Extensive Burns: A Single-Centre Randomised Controlled Trial

Status:

Version 1

Abstract

Figures

Introduction

Methods

Statistical analysis

Results

Discussion

Conclusion

Abbreviations

Declarations

References

Additional Declarations

Status:

Version 1