Abstract

Background: Perioperative fluid management is critical in neurosurgery as over perfusion can lead to brain edema whereas under perfusion may lead to brain hypoperfusion or ischemia. We aimed to determine the effectiveness of intraoperative goal-directed fluid therapy (GDFT) in patients undergoing intracranial surgeries.

Methods: We searched MEDLINE, Cochrane, and PubMed databases and forward-backward citations for studies published between database inception and February 22, 2024. Randomized controlled trials where intraoperative GDFT was performed in neurosurgery and compared to the conventional regime were included in the study. GDFT was compared with the conventional regime as per primary outcomes – total intraoperative fluid requirement, serum lactate, hemodynamics, brain relaxation, urine output, serum biochemistry, and secondary outcomes – intensive care unit and hospital length of stay. The quality of evidence was assessed with the Cochrane risk of bias tool. This study is registered on PROSPERO (CRD42024518816).

Results: Of 75 records identified, eight were eligible, the majority of which had a low to moderate risk of overall bias. In four studies, more fluid was given in the control group. No difference in postoperative lactate values was noted in 50% of studies. In the remaining 50%, lactate was more in the control group. Three out of four studies did not find any significant difference in the incidence of intraoperative hypotension, and four out of six studies did not find a significant difference in vasopressor requirement. The majority of studies did not show significant differences in urine output, brain relaxation, and length of stay between both groups. None found any difference in acid base status or electrolyte levels.

Conclusion: GDFT, when compared to the conventional regime in neurosurgery, showed that the total volume of fluids administered was lesser in the GDFT group with no increase in serum lactate. There was no difference in the hemodynamics, urine output, brain relaxation, urine output, length of stay, and biochemical parameters.

Keywords: Fluid management, Goal-directed fluid therapy, Neuroanesthesia, Neurosurgery

INTRODUCTION

Optimal fluid administration during the intraoperative period is a vital component in the management of surgical patients. Hypovolemia, on the one hand, can lead to inadequate organ perfusion. Whereas, hypervolemia can cause interstitial edema, decreased tissue healing, local inflammation, increased wound infection, and wound dehiscence.[ 14 ] A change in fluid management strategy introduced alone on the day of surgery itself is shown to reduce perioperative complications by 50%.[ 14 ] A wide variety of intraoperative fluid administration practices are being followed, but the three major strategies of fluid management can be divided into “restricted,” “liberal,” and “goal-directed.”[ 1 ] Goal-directed fluid therapy (GDFT) can be defined as the technique aimed at achieving maximum tissue oxygen delivery by titrating fluids, vasopressors, or inotropes to a predefined physiological target hemodynamic value.[ 25 ] There are emerging evidences that show the advantages of GDFT in terms of decreased complication rate, morbidity, and mortality, especially in major surgery.[ 5 , 6 , 21 ] In spite of the favorable evidence, GDFT is still not widely implemented in routine clinical practice.[ 25 ] In most neurosurgical procedures, fluid management can be affected by various factors, such as major fluid shifts, the use of osmotic diuretics, and prolonged surgical duration. A low fluid input can lead to decreased cerebral perfusion and excessive fluid can result in cerebral edema.[ 10 ] Studies have been done to assess the effect of GDFT in the neurosurgical patient population, targeting various parameters such as pulse pressure variation (PPV), stroke volume variation (SVV), and cardiac index (CI) with variable results.[ 10 , 12 , 16 ] Hence, this systematic review was conducted with the objective of determining the effectiveness of intraoperative GDFT in patients undergoing intracranial surgeries.

MATERIALS AND METHODS

The current systematic review was conducted as per the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement.[ 20 ] The review was registered in the International Prospective Register of Systematic Reviews (PROSPERO; CRD42024518816).

Objective

The objective of this study was to determine the effectiveness of intraoperative GDFT in patients undergoing intracranial surgeries with regard to the following outcome variables:

Primary outcomes

Total intraoperative fluid requirement

Secondary outcomes

Intensive care unit (ICU) and hospital length of stay.

Study selection criteria

Patient groups

Adult patients (over 18 years) undergoing elective or emergency craniotomy surgery were included in the study. The studies were not limited in terms of the type or location of the intracranial pathology.

Intervention and comparison

The patient participants had to be randomly assigned to either receive GDFT or conventional fluid management intraoperatively. We defined intraoperative GDFT as any fluid administration guided by continuously measured hemodynamic variables targeted to maximize tissue perfusion and oxygen delivery. These hemodynamic variables included cardiac output, stroke volume, SVV, PPV, or other factors, as measured by any device. Studies in which the control group also received any other form of GDFT were excluded from the study. Conventional fluid management was considered in the form of protocol-driven standard care, for example, maintaining mean arterial pressure > 65 mmHg or central venous pressure (CVP) >8 mmHg or care at the discretion of the attending physicians.

Types of studies

Randomized controlled trials (RCTs) where intraoperative GDFT was performed in adult patients scheduled for intracranial surgery. Non-randomized trials, cohort studies, retrospective studies, animal model trials, studies with incomplete text, and studies in languages other than English were excluded from the study.

Search strategies and data collection

The literature search was conducted on PubMed, MEDLINE, and Science Direct. Keywords for database search included the terms “goal-directed fluid neurosurgery.” The last search was done on February 22, 2024. Independent reviewers screened the articles for titles and abstracts. Studies were “included” if the selection criteria were met. In case of doubt, if any, they were resolved by the other author. Full-text articles were retrieved. The final inclusion of any study was based on full-text reading. Two review authors independently extracted data from the included studies, and a third review author rechecked the data. The reference lists were scanned, and any relevant citations were identified and included for analysis. A spreadsheet-based data extraction form was used to collect study information. We extracted the following study characteristics:

General information: Year of study

As only qualitative analysis of available data was planned, alternative data synthesis methods and meta-analyses were not considered.

Risk of bias assessment

The risk of bias and the certainty assessment were done by risk of bias-2 by two review authors.[ 26 ] Disagreements were resolved by discussion or by consultation with another review author. We assessed the risks of bias according to the following domains:

Random sequence generation

Studies were considered to be at low risk of bias if they adequately met the first five criteria with no evidence of significant selective reporting bias or any other major sources of bias.

RESULTS

Literature search and study selection

PubMED, Science Direct and Cochrane search initially retrieved 75 citations with 7 RCTs meeting the inclusion criteria [PRISMA Flowchart, Figure 1 ].[ 8 , 10 , 12 , 16 , 18 , 24 , 27 ] From the list of references, one study was deemed suitable and was added to the final pool of studies for review.[ 29 ] Hence, the final number of studies included was n = 8. (572 patients).

Figure 1:

PRISMA flow chart depicting the study selection process. PRISMA: Preferred Reporting Items for Systematic Reviews and Meta-Analyses.

The studies included in this review were heterogeneous and varied in design [ Table 1 ]. As the studies were heterogeneous, statistical pooling and meta-analysis were not possible. Narrative synthesis by making a qualitative summary of available data was performed on 8 RCTs.

Baseline characteristics of included RCTs

The salient baseline characteristics of included RCTs are shown in Table 1a . The patient population in all the studies included adults except Sae-Phua et al., who conducted a study in elderly patients aged >60 years.[ 24 ] The majority of the patients in all the trials belonged to the American Society of Anesthesiologists, physical status I–II. In seven studies, only elective surgeries were included from the study. The nature of surgery, whether elective or emergency, was not mentioned by Sundaram et al.[ 27 ] Only supratentorial lesions were included in four studies.[ 8 , 10 , 18 , 29 ] Two studies included both supra- and infratentorial lesions.[ 24 , 27 ] The data regarding the intracranial location of the lesion were not mentioned by Luo and Hrdy et al.[ 12 , 16 ] Only intracranial tumors were included by five authors.[ 8 , 10 , 18 , 27 , 29 ] Two studies incorporated both tumors and aneurysms in their studies.[ 16 , 24 ] The type of intracranial pathology was not specified by Hrdy et al.[ 12 ]

As per the risk of bias assessment tool, the overall score was two for three studies,[ 12 , 24 , 27 ] three for three studies,[ 8 , 10 , 18 ] four for one study,[ 16 ] and six for one study[ 29 ] [ Table 1b ]. Blinding of participant and personnel was mentioned only by Gopal et al.[ 8 ]

Table 1a:

PICO characteristics of included trials.

Table 1b:

Risk of bias assessments for randomized control trials using RoB-2.

Three (37.5%) studies considered PPV as the therapeutic goal for GDFT.[ 8 , 10 , 27 ] The remaining 5 (62.5%) studies used SVV to guide GDFT.[ 12 , 16 , 18 , 24 , 29 ] The therapeutic values were obtained using an invasive arterial line in all the studies except by Hrdy et al., who utilized a non-invasive hemodynamic system.[ 12 ] In all eight studies, a fluid bolus was given as the first line of intervention in the GDFT group, with crystalloid bolus given in 4 (50%) studies[ 8 , 10 , 24 , 27 ] and colloid bolus in 4 (50%) studies.[ 12 , 16 , 18 , 29 ] The specific hemodynamic monitoring technique used was the GE solar 8000M/I monitor by Hasanin et al.[ 10 ] Four authors used the Flotrac Vigileo monitor.[ 16 , 18 , 24 , 29 ] A non-invasive (Starling SV hemodynamic monitor, Cheetah Medical Inc., 600SE Maritime Ave Suite 220, Vancouver, WA, USA) was utilized in only 1 study by Hrdy et al.[ 10 ] Sundaram et al. used the Philips Intellivue MP50 monitor.[ 27 ] The hemodynamic monitoring technique was not mentioned by Gopal et al.[ 8 ] The hemodynamic target for GDFT was variable, with three studies considering PPV of <13%,[ 8 , 10 , 27 ] two studies considering CI >2.5 L/min/m², SVV <15%,[ 12 , 16 ] and three studies targeting CI >2.5 L/min/m², SVV<12%.[ 18 , 24 , 29 ]

Primary outcomes

Total intraoperative fluid requirement

The total intraoperative fluid requirement was significantly higher in the control group in 3 (37.5%) studies [ Table 2 ].[ 8 , 16 , 24 ] However, in 2 (25%) studies, more fluid was received by the intervention (GDFT) group.[ 10 , 29 ] Mishra et al. found that the total crystalloids infused were higher in the control group, but the amount of total fluid and total colloid were comparable.[ 18 ] Hrdy et al. observed that the GDFT group received significantly less crystalloid but more colloid than the control group.[ 12 ] Sundaram et al. found that the GDFT group received more crystalloids but similar colloids as compared to the control group.[ 27 ]

Table 2:

Primary outcomes.

Serum lactate levels

Serum lactate levels at the end of surgery were significantly higher in the control group than in the GDFT group in 4 (50%) studies [ Table 2 ].[ 10 , 16 , 18 , 29 ] Gopal et al. and Sundaram et al. observed the baseline, postoperative, and rise in serum lactate levels. Both studies found no significant difference in lactate levels at all-time points.[ 8 , 27 ] Similarly, 2 (25%) studies also found no statistical difference in the postoperative lactate levels between both groups.[ 12 , 24 ]

Intraoperative hemodynamics

Four authors mentioned the incidence of intraoperative hypotension [ Table 3 ].[ 8 , 12 , 18 , 24 ] Gopal et al. found that the incidence of intraoperative hypotension was more in the group receiving CVP-guided fluids.[ 8 ] Whereas, the rest three studies did not find any significant difference in the incidence of hypotension between both the groups.[ 12 , 18 , 24 ] The vasopressor requirement was noted in six studies.[ 8 , 10 , 12 , 16 , 24 , 29 ] Of which 4 (50%) studies noticed no significant difference in the vasopressor requirement between both groups.[ 8 , 10 , 12 , 29 ] Luo et al. found that the number of patients requiring metaraminol and ephedrine was significantly higher in the GDFT group.[ 16 ] However, Sae-Phua et al. observed that the GDFT group received significantly less ephedrine than the control group.[ 24 ] Sundaram et al. studied the fall in BP (>20% from baseline) and heart rate between the groups and found them to be comparable among both groups.[ 27 ]

Table 3:

Secondary outcomes.

Brain relaxation

Six out of eight studies studied brain relaxation in both groups [ Table 2 ].[ 8 , 10 , 12 , 18 , 24 , 29 ] In only one out of the six studies, it was found that the occurrence of tight brain was higher in the control group, with the brain relaxation score (BRS) being significantly higher in the control population.[ 18 ] The BRS was comparable between both groups in three studies.[ 8 , 10 , 24 ] Hrdy et al. noted the patients with brain edema requiring intervention and found no incidence of brain edema in any group.[ 12 ] Similarly, the degree of brain edema was comparable in both groups in the study by Wu et al.[ 29 ]

Urine output

Seven out of eight studies noted the urine output of patients [ Table 2 ].[ 8 , 10 , 12 , 16 , 18 , 24 , 29 ] The urine output was similar between both groups in five studies.[ 12 , 16 , 18 , 24 , 29 ] In only one study, it was found that the urine output was significantly higher in the control group.[ 8 ] Whereas Hasanin et al. found that the urine output was more in the GDFT group.[ 10 ]

Serum biochemistry

Six out of eight studies examined the serum biochemical parameters, that is, pH and electrolytes [ Table 2 ].[ 10 , 16 , 18 , 24 , 27 , 29 ] None of the studies found any difference in the acid-base status or electrolyte levels between the groups.

Secondary outcomes

ICU and hospital length of stay

Six out of eight studies examined the ICU and hospital length of stay of patients [ Table 3 ].[ 10 , 12 , 16 , 18 , 24 , 29 ] Only one study found that the ICU length of stay and the ICU costs were more in the control group.[ 16 ] The rest of the studies found no significant difference in the ICU and hospital length of stay between both groups.[ 10 , 12 , 18 , 24 , 29 ]

DISCUSSION

This systematic review included eight RCTs comparing GDFT with conventional regimes for intraoperative fluid administration in neurosurgery with a total of 572 patients.

It was found that in the majority of studies that compared the total intraoperative fluid administration, more fluid was given in the control group. The postoperative serum lactate values were similar between both groups in 50% of the studies. Whereas in the remaining half studies, it was found to be more in the control group. Regarding hemodynamics, the majority of studies did not find any significant difference in the incidence of intraoperative hypotension and vasopressor requirement in both groups. Similarly, in a greater number of studies, there was no significant difference in the urine output, brain relaxation, and length of stay between both groups. None of the studies found any difference in the acid-base status or electrolyte levels between the groups.

The main aim of perioperative fluid management is to maintain an optimum cardiac output and tissue perfusion. GDFT utilizes certain hemodynamic targets such as PPV, SVV, and CI to identify the fluid responsiveness of patients. This helps in preventing fluid overload in patients and the deleterious effects such as pneumonia, respiratory failure, pulmonary edema, and delayed wound healing.[ 11 ] GDFT has been shown to be beneficial in studies.[ 13 , 15 ] In a meta-analysis of 6325 patients, Giglio et al.[ 7 ] analyzed the effect of GDFT on postoperative complications in different surgeries. They concluded that GDFT was beneficial in abdominal surgery, orthopedic surgery, and neurosurgery in terms of a decrease in postoperative complications.

Perioperative fluid management is critical in neurosurgery as over perfusion can lead to brain edema, whereas under perfusion may lead to brain hypoperfusion or ischemia. Other concerning points specific to neurosurgery are the use of osmotic diuretics, the significance of the type of fluid used, the probability of long duration surgeries, major fluid shifts, difficult assessment of blood loss under the drapes, intraoperative diabetes insipidus, and distinct type of surgeries such as vascular surgeries which require unique fluid management. Thus, it becomes essential to use a proper parameter to guide fluid management in neurosurgery. To date, only one meta-analysis has been done, which individually evaluated the effect of GDFT on neurosurgical patients.[ 7 ]

As per the results, it is seen that the majority of the authors found that the intraoperative fluid administration was higher in the group following the conventional fluid management strategy.[ 8 , 16 , 18 , 24 ] As per Gopal et al., more fluid administration in the control group was attributed to the conventional method of calculating cumulative losses accounting for vasodilation during anesthetic induction, estimated blood loss, and urine output every hour.[ 8 ] In addition, 100 mL fluid boluses were given whenever CVP was <8 mmHg. Whereas in the GDFT group, conventional calculation of fluid administration was not used and only PPV-guided fluid bolus was given along with the maintenance fluid. In spite of receiving lesser total fluid by the GDFT group, in all the above four studies, the lactate levels were not higher than in the control group which suggests that GDFT can maintain adequate organ perfusion with less fluid intake. Luo et al. also observed that the GDFT group did not develop any hypovolemia related complications such as acute kidney injury or myocardial injury.[ 16 ] Improved fluid balance could be beneficial in patients who are prone to fluid overload, such as patients with severely impaired cardiac or kidney function. In an RCT studying perioperative GDFT using noninvasive pleth variability index monitoring in gynecologic oncology surgery, it was observed that the amount of intraoperatively administered crystalloid solution was significantly lower in patients who received GDFT.[ 30 ] The authors also found a stable serum lactate concentration, reduced postoperative complications, and ICU admissions. However, the OPTIMISE trial, which evaluated the effectiveness of cardiac output-guided hemodynamic therapy in major gastrointestinal surgery, found no difference in the intravenous fluid volume infused in both the intervention and conventional groups.[ 21 ]

It was observed that the serum lactate levels were either similar or higher in the control group. It is noteworthy that in none of the studies the serum lactate was higher in the patients receiving GDFT. This point indicates that GDFT might be able to maintain adequate end organ perfusion. A retrospective cohort study demonstrated that elevated intraoperative serum lactate in craniotomy patients is associated with new neurological deficits and longer length of stay.[ 3 ] The authors suggested that in some cases, serum lactate may be an early marker of regional cerebral hypoperfusion. Perioperative lactate values from microdialysis catheters have shown the relation of lactate with neurological outcomes.[ 2 ] Whether the results from microdialysis studies can be extrapolated to serum lactate values which should be studied more.

In our review, we only included studies comparing GDFT versus conventional fluid management in neurosurgery. However, few other studies in the literature have compared two different methods of GDFT in neurosurgery. PPV or SVV constitute the dynamic variables for predicting fluid responsiveness with no fixed single cut off value. Both these parameters have a “gray zone” of two cutoffs within which the validity is inconclusive.[ 4 ] Wu et al. investigated GDFT protocols based on two SVV cut offs in the grey zone in supratentorial tumor resection.[ 28 ] The authors compared two cutoff values for SVV, that is, 10% and 18%. They found that the low SVV group (10%) received a higher volume of colloid, had a higher urine output, higher average cardiac index, shorter ICU stay, fewer postoperative neurological events, attenuated changes in the neuronal biomarker levels, lower intraoperative serum lactate, and a higher Barthel index at discharge. Overall, the authors concluded that fluid boluses targeting a lower SVV are more beneficial than a restrictive protocol.

Another RCT by Nayak et al. compared PPV with pleth variability index (PVI) in patients undergoing supratentorial lesion surgeries.[ 19 ] It was seen that Both PVI- and PPV-guided GDFT showed no significant difference in the postoperative lactate values, mean total fluid administered, mean blood loss, length of ICU stay, and emetic and hypotension episodes. Authors concluded that PVI is comparable to PPV to guide GDFT regarding tissue perfusion and postoperative complications. However, it was mentioned that both the parameters had low sensitivity and specificity as far as GDFT was concerned.

PPV and SVV both serve as a reliable dynamic parameter to assess fluid responsiveness provided that the physiological limitations are avoided.[ 17 ] Many of these limitations, such as atrial fibrillation, spontaneous breathing activity, and low tidal volume, are usually excluded in patients intraoperatively under general anesthesia. Unlike SVV, PPV monitoring has the practical advantage of the non-requirement of any extra cardiac output monitoring device. SVV and PPV have been shown to have comparable performance in predicting fluid responsiveness in patients undergoing major surgeries. PPV monitoring is cost-effective since the SVV transducer is more expensive. Furthermore, we are almost regularly putting an arterial line for invasive BP monitoring in neurosurgery. Hence, targeting PPV as a guide to monitor fluid administration intraoperatively can be proposed as a feasible option in neuroanesthesia.

Hrdy et al. utilized a non-invasive method of assessing stroke volume for GDFT.[ 12 ] The Starling SV monitor is completely non-invasive and is based on the principle of bio-impedance. Furthermore, it does not require any external calibration. As per the meta analysis by Peyton and Chong, bio-impedance-based methods can be compared to invasive monitors in terms of accuracy.[ 22 ] Thus, non-invasive cardiac output monitors can also prove to be useful as a tool for perioperative GDFT.

Luo et al. observed that in the GDFT group, the ICU expenses were significantly lower than in the conventional group.[ 16 ] The authors linked this reduction in expenses to the decreased length of ICU stay and lesser complications in the GDFT cohort. A cost-effectiveness analysis of the large scale OPTIMISE trial also found that perioperative cardiac output-guided hemodynamic therapy algorithm was associated with an average cost reduction of £400.[ 23 ] A similar reduction in total hospital cost in the GDFT group was reported by Hand et al. in cases of head and neck cancer.[ 9 ] These findings indicate that not only clinically, GDFT might help in reducing the economic burden.

However, our systematic review had few limitations. The study population was heterogeneous. Sae-Phua et al. included only elderly patients aged more than 60 years, unlike the rest of the studies.[ 24 ] The type of neurosurgical lesion also was not homogenous in all the studies which can have an impact on the outcomes parameters. Only qualitative analysis of the studies was done. No statistical meta-analysis was performed. The brain relaxation scores assessed can be subjective. Different authors also varied the approach and targets to achieve GDFT. Finally, all the included trials in our review were single centered.

The strength of our systematic review is that all the included studies were relatively new, that is, within the year 2016–2023. No other review has been done in the literature exclusively assessing GDFT in the neurosurgical patient population.

CONCLUSION

Perioperative optimal fluid management plays an important role in neurosurgical patients. GDFT, when compared to conventional regime in neurosurgery showed that the total volume of fluids administered was lesser in the GDFT group with no increase in serum lactate levels. However, there was no difference in the hemodynamics, urine output, brain relaxation, urine output, length of stay, and biochemical parameters. More large scale trials should be done with a homogeneous cohort to establish an optimal perioperative fluid management regime in neurosurgical patients.

Ethical approval

The Institutional Review Board approval is not required.

Declaration of patient consent

Patient’s consent was not required as there are no patients in this study.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

Use of artificial intelligence (AI)-assisted technology for manuscript preparation

The authors confirm that there was no use of artificial intelligence (AI)-assisted technology for assisting in the writing or editing of the manuscript and no images were manipulated using AI.

Disclaimer

The views and opinions expressed in this article are those of the authors and do not necessarily reflect the official policy or position of the Journal or its management. The information contained in this article should not be considered to be medical advice; patients should consult their own physicians for advice as to their specific medical needs.

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