Effects of controlled low central venous pressure on organ function during hepatectomy: Current progress

Abstract

Hepatectomy is an effective and widely adopted surgical technique for treating various liver diseases. However, owing to the liver’s unique anatomical structure and rich blood supply, hepatectomy poses considerable challenges. The most critical challenge is intraoperative bleeding, which is closely associated with postoperative complications and patient mortality. This has driven the pursuit of effective and safe strategies to minimize bleeding during hepatectomy. Managing a low central venous pressure of <5 cm H₂O or 3 mmHg has been shown to significantly reduce hepatic vein bleeding and provide optimal surgical visibility during hepatectomy. Before the routine application of low central venous pressure management, bleeding during hepatectomy was often associated with unacceptably high morbidity and mortality rates. Although this technique has been demonstrated to be safe and effective in multiple studies of hepatectomy and transplantation, its widespread adoption remains limited. Concerns have been raised regarding morbidity related to insufficient perfusion to vital organs during the low central venous pressure phase of hepatectomy. This review has discussed recent developments concerning the effects of low central venous pressure management during hepatectomy on the function of critical organs.

Introduction

Hepatocellular carcinoma (HCC), also known as malignant liver cancer, is one of the most lethal cancers because of its complexity, postoperative recurrence and metastasis, and marked heterogeneity. ¹ Many cancerous and noncancerous liver lesions are treated by partial removal of the liver (hepatectomy), a major surgical procedure associated with substantial mortality and morbidity and a high risk of complications, including blood loss during liver parenchymal transection. ² Postoperative bleeding after hepatectomy is considered a key factor affecting postoperative prognosis. Consequently, various strategies and surgical techniques have been developed to reduce transfusion requirements and thereby decrease postoperative complications. Central venous pressure (CVP) plays a crucial role in reducing blood loss during hepatectomy. A CVP of 1–5 mmHg is considered an optimal target, when combined with vascular control, to minimize blood loss. ³ Any strategy that reduces blood loss and transfusion requirements during hepatectomy is beneficial for both patients and surgeons. ⁴ Intraoperative or postoperative massive blood loss and transfusion are associated with risks such as infectious diseases, acute respiratory distress syndrome, coagulation disorders, and multi-organ failure and may also promote tumor recurrence because of immunosuppressive effects. ⁵

Methods

We searched PubMed, Web of Science, Embase, and the Cochrane Library using the keywords “low central venous pressure” and “hepatectomy” to identify clinical studies that reported postoperative recovery of organ function. Eligible study designs included randomized controlled trials and observational studies, both prospective and retrospective. A total of 21 articles were included, addressing postoperative liver function, renal function, gastrointestinal function, and coagulation systems.

Methods to control low CVP

Fluid infusion strategy

Absolute fluid restriction refers to reducing effective blood volume and low CVP (LCVP) through the use of diuretics, hemodilution, and related measures. In contrast, relative volume redistribution reduces CVP and venous return through vasodilation induced by nitrates, volatile anesthetics, or epidural anesthesia. A randomized controlled study by Zatloukal et al. ⁶ (2017) found no significant differences in effectiveness or safety between these two approaches for lowering CVP. Patients in the absolute fluid restriction group received less fluid preoperatively but experienced a slightly longer hospital stay. The study also reported reduced intraoperative bleeding and transfusion rates when the Pringle maneuver was applied. Unlike previous studies that primarily compared different fluid types or volumes, this study focused on the choice of fluid management strategy. However, the relatively small sample size limited its statistical power, and the analysis mainly addressed intraoperative hemodynamics and tissue perfusion, with less emphasis on postoperative recovery and complication rates. These findings suggest the need for further investigation into the applicability of absolute fluid restriction and relative volume redistribution strategies for different patient and surgical characteristics. Additional research on the effects of fluid management strategies on postoperative recovery and complication rates may help optimize perioperative management and improve the long-term prognosis after hepatectomy. ⁶ With regard to intraoperative fluid management, Weinberg et al. ⁷ previously developed a cardiac output-guided algorithm to optimize fluid therapy and oxygen delivery in patients undergoing pancreatic surgery. This approach was subsequently adapted for patients undergoing complex hepatectomy and termed as goal-directed fluid therapy (GDFT). In 2019, a retrospective observational study compared intraoperative fluid and vasoactive drug administration, postoperative complications, and length of hospital stay between patients undergoing LCVP hepatectomy managed with GDFT and those managed with conventional fluid strategies. The results showed that GDFT, guided by a cardiac output-based algorithm, reduced intraoperative fluid administration and postoperative complications and was associated with a shorter hospital stay compared with conventional management (see Figure 1). ⁷

Body posture

In surgical practice, changes in patient positioning are common. For example, the beach chair position is frequently used in shoulder surgery, the head-down-feet-up position in pelvic surgery, and the prone position in lumbar spine surgery. Appropriate positioning can improve exposure of the surgical field, reduce technical difficulty, and provide optimal ergonomics for the surgeon. A retrospective study by Soonawalla et al. ⁸ (2008) showed that the reverse Trendelenburg position (head elevated, legs lowered) could rapidly and consistently reduce CVP, with a mean decrease to 1.7 mmHg. During surgery, no unexplained episodes of hypoxia, hypotension, or fluctuations in end-tidal CO₂ were observed. Postoperatively, two patients showed increased serum creatinine levels, and three developed long-term renal dysfunction; these findings were attributed to anesthetic effects and were consistent with incidence rates reported in other studies. Overall, although postoperative hemoglobin levels decreased, no significant renal impairment was observed. These results suggest that the reverse Trendelenburg position not only reduces bleeding and transfusion requirements during hepatectomy but may also lower the risk of postoperative renal dysfunction. However, this study had limitations, including a small sample size of only 50 patients and a nonrandomized design. In addition, the absence of a control group without the reverse Trendelenburg position precluded comparison with other positioning strategies and limited conclusions regarding its relative advantages. Further research is therefore needed to clarify the effects of the reverse Trendelenburg position on renal function and to determine whether its combined use with other interventions could further improve surgical outcomes. ⁸ Regarding the effect of intraoperative positioning on CVP, a double-blind randomized clinical trial by Pan et al. ⁹ (2020) reported that CVP increased significantly after establishment of pneumoperitoneum during laparoscopic hepatectomy, rising by 10–14 cm H₂O compared with baseline values. Switching to the reverse Trendelenburg position resulted in a significant reduction in CVP, and controlled LCVP during liver parenchymal transection further decreased these values. Postoperatively, CVP returned to normal levels. ⁹ Overall, adjustment of body position can assist anesthesiologists in achieving lower CVP during hepatectomy (see Figure 1).

Intraoperative ventilation strategies

Based on the theory of cardiopulmonary interaction, cyclic changes in intrathoracic pressure during respiration lead to corresponding changes in hemodynamic parameters such as CVP, venous return (VR), stroke volume (SV), and cardiac output (CO).^10,11 Geerts et al. reported that CVP changes induced by positive end-expiratory pressure (PEEP) can also predict volume responsiveness, suggesting that different ventilation modes may influence CVP. ¹² In a prospective study by Sand et al. (2011), increasing PEEP from 5 to 10 cm H₂O led to a slight rise in CVP and hepatic venous pressure (HVP), although the increase was minimal. PEEP is beneficial for improving ventilation and gas exchange, and the authors concluded that its advantages outweighed potential hemodynamic risks. Additionally, the study found that the head-up position did not reduce HVP, indicating no clear benefit for its use in open hepatectomy. This finding appears to contrast with previous conclusions regarding the reverse Trendelenburg position, possibly due to the small sample size in Sand et al.’s study. Further large-scale randomized controlled trials are needed to determine the optimal positioning strategy for LCVP hepatectomy. The study considered only changes in HVP and CVP, without accounting for other potential influencing factors. ¹³ Protective mechanical ventilation strategies typically include tidal volumes of 6–8 mL/kg (predicted body weight), PEEP of 6–8 cm H₂O, and recruitment maneuvers every 30 min, whereas nonprotective strategies involve tidal volumes of 10–12 mL/kg (predicted body weight), zero PEEP, and no recruitment maneuvers. In a cohort study of 79 patients, Neuschwander et al. ¹⁴ (2016) reported that protective ventilation strategies, including low tidal volume, moderate PEEP, and repeated recruitment maneuvers, did not increase intraoperative bleeding during hepatectomy. Although limited by a small sample size and potential selection bias, the study did not provide a detailed assessment of postoperative bleeding or complications, leaving the impact of protective ventilation strategies on postoperative outcomes incompletely evaluated. These findings highlight the need for further exploration of protective ventilation effects on postoperative bleeding and complications as well as optimization of specific parameters and methods. ¹⁴ In 2017, Iguchi et al. ¹⁵ conducted a cohort study involving 41 participants and investigated the use of low airway positive pressure without PEEP to reduce bleeding during living donor hepatectomy. The study demonstrated that intraoperative bleeding was significantly lower in the low positive airway pressure (PAP) group compared with that in the standard PAP group. Multivariate regression analysis identified low PAP and CVP during hepatectomy as predictors of intraoperative blood loss. This study addressed limitations of previous research by examining the effect of low airway pressure ventilation on blood loss and its correlation with CVP. It elucidated the mechanism by which low airway pressure ventilation reduces bleeding during hepatectomy, offering new insights for intraoperative blood management. These findings provide guidance for anesthesiologists in selecting appropriate ventilation strategies during hepatectomy to minimize intraoperative bleeding and enhance surgical safety (see Figure 1). ¹⁵

Vasodilator drugs

The choice of vasopressive and vasodilatory agents varies across countries and institutions, often influenced by local healthcare practices and economic considerations. Among the many available drugs, research has identified several drugs that are considered safe for clinical use. Vasodilators play an important role in further reducing CVP. As early as 2011, Ryu et al. ¹⁶ studied LCVP management in living donor liver surgery and found that milrinone provided a more favorable surgical environment and stable hemodynamics. In this randomized study, 38 healthy adult liver donors were assigned to either a milrinone group or a saline group. Both groups maintained stable vital signs, but the milrinone group required fewer vasopressors and diuretics to maintain LCVP and demonstrated faster postoperative recovery. Milrinone-induced LCVP improved the surgical field, reduced bleeding, and positively influenced intraoperative hemodynamics and postoperative recovery. ¹⁶ Subsequently, in 2021, Yang et al. ¹⁷ compared the vasodilatory effects of nitroglycerin and milrinone. They conducted a randomized controlled trial, which indicated that the milrinone group experienced less intraoperative bleeding and lower total blood loss during hepatectomy. Additionally, patients in the milrinone group had higher postoperative hemoglobin levels and blood pH values as well as shorter durations of drainage tube placement and postoperative hospital stay compared with the nitroglycerin group. Overall, milrinone appears to be a superior choice to traditional nitroglycerin for controlling LCVP during hepatectomy. ¹⁷ This study comparing the effectiveness of milrinone and nitroglycerin provides a new pharmacological option for reducing CVP in hepatectomy. It offers a comprehensive assessment of the two drugs by monitoring hemodynamic parameters and blood indices. However, the relatively small sample size may limit the reliability and generalizability of the results. Being a single-center study, it may have regional and population-specific limitations, and without stratified analyses for different patient conditions or surgical types, potential confounding factors cannot be excluded. Future research should include large-scale, multicenter trials to evaluate not only short-term efficacy in open hepatectomy but also long-term outcomes in minimally invasive procedures (see Figure 1). ¹⁸

Subhepatic inferior vena cava occlusion

In 2011, Rahbari et al. ¹⁹ conducted a randomized controlled study involving 128 participants and found that infrarenal clamping of the inferior vena cava significantly reduced intraoperative bleeding compared with conventional anesthesia-based methods for lowering CVP. The technique was proposed as an effective strategy to maintain hemodynamic stability during surgery. However, the study also noted that inferior vena cava clamping could increase the risk of postoperative pulmonary embolism. This study compared the effects of infrarenal clamping of the inferior vena cava with anesthetic methods for reducing CVP on blood loss during hepatectomy. Multiple secondary endpoints were considered to comprehensively evaluate the efficacy and safety of the clamping technique versus anesthetic approaches. Limitations included the relatively small sample size, which may affect result reliability, and the focus on specific hepatectomy techniques, potentially limiting generalizability to other surgical approaches. Additionally, the study did not control for other factors that could influence intraoperative bleeding. ¹⁹ Prompted by this research, Junrungsee et al. ²⁰ (2021) conducted a similar randomized controlled study with 120 participants. They reported that infrarenal clamping of the inferior vena cava significantly reduced total intraoperative bleeding and bleeding during liver resection. The postoperative hemodynamic status was more stable in this group, with reduced need for vasopressors to maintain blood pressure and a lower incidence of postoperative complications, resulting in faster recovery. The study concluded that infrarenal clamping of the inferior vena cava, combined with anesthesia techniques, is a safe method for reducing bleeding during hepatectomy and can be applied in feasible situations regardless of CVP values, particularly in large and complex hepatectomies. However, similar to the 2011 study, this research was limited by a small sample size, potential selection bias, and lack of consideration of other factors that could influence intraoperative bleeding, such as surgical duration and technique. The study also did not provide a detailed analysis of postoperative complications. ²⁰ Future research should aim to increase sample sizes to reduce bias, investigate additional factors affecting intraoperative bleeding through multifactorial analyses, and incorporate the effects of LCVP on postoperative complications. Such comprehensive studies would offer a more robust understanding of the efficacy and safety of combining infrarenal clamping of the inferior vena cava with anesthesia techniques in hepatectomy.

Influence

Hemodynamics

The mean arterial pressure (MAP) is calculated as CO multiplied by systemic vascular resistance (SVR), with CO determined by SV and heart rate (HR). SV is linked to preload (according to Starling’s law); therefore LCVP can affect CO, potentially leading to systemic hypotension. ²¹ Although controlled LCVP techniques are increasingly employed in hepatectomy, maintaining LCVP can markedly reduce effective circulating blood volume due to interventions by surgeons and anesthesiologists. This reduction may result in insufficient CO to meet the perfusion requirements of vital organs. Both initial ischemic damage and reperfusion injury during postoperative fluid resuscitation pose serious threats to organ function, potentially leading to a range of complications. A study by Wang et al. ²² (2020) showed that patients managed with LCVP had significantly lower MAP, likely attributable to interventions such as restricting infusion volume, increasing anesthesia depth, and using vasodilators. However, the absence of significant differences in HR and urine output (UO) between the groups suggested that adequate organ perfusion was maintained. The current evidence on the impact of hemodynamics is limited by small sample sizes and a lack of sensitive indicators for organ perfusion. ²² Large-scale randomized controlled trials are needed to strengthen evidence on the effects and safety of LCVP management on systemic hemodynamics and organ perfusion. Such studies will improve the understanding of the balance between minimizing intraoperative bleeding and maintaining adequate organ perfusion, ultimately optimizing patient outcomes.

Liver

A 2013 study by Wagener et al. ²³ emphasized the importance of assessing liver function, surgical indications, and postoperative management in patients with underlying liver disease undergoing hepatectomy. For non-cirrhotic patients, hepatectomy safety can be assessed using the ratios of remnant liver volume to body weight (RLV/BW) and remnant liver volume to total liver volume (RLV/TLV). In cirrhotic patients, hepatectomy safety primarily depends on the RLV/TLV ratio, with values below 40% generally considered a high-risk factor for postoperative liver failure. Additionally, the model for end-stage liver disease (MELD) score, initially developed to predict survival after transjugular intrahepatic portosystemic shunt (TIPS) procedures, has been recognized since 2002 as a reliable predictor of short-term mortality in liver transplant candidates. ²³ Regarding postoperative liver function, using the criteria proposed by Balzan et al., ²⁴ Wu et al. ²⁵ (2021) evaluated the incidence of liver dysfunction, defining postoperative liver dysfunction as serum total bilirubin >50 μmol/L and/or prothrombin activity <50% on the fifth postoperative day. Patients were divided into two groups based on the use of controlled LCVP (CLCVP) techniques. In patients undergoing major laparoscopic hepatectomy—defined as resection of more than three liver segments, which carries higher mortality and complication risks ²⁵ —the incidence of postoperative liver dysfunction was 21.23% in the CLCVP group, not significantly different from the 21.54% in the non-CLCVP group. However, the use of CLCVP reduced intraoperative bleeding, improved surgical field visibility, shortened operative duration, and decreased cumulative hepatic vascular occlusion time at the hepatic hilum, thereby reducing overall surgery and anesthesia time. These benefits occurred without negatively affecting postoperative hospital stay, intensive care unit (ICU) stay, or in-hospital mortality. ²⁵ In summary, CLCVP is a simple and effective method to reduce blood loss and transfusion requirements during hepatectomy and does not appear to adversely affect liver function. This finding highlights the potential advantages of LCVP management in liver surgery, particularly for complex and extensive resections. ⁵

Kidney

A retrospective study by Correa-Gallego et al. ²⁶ (2014), including 2116 patients from 2003 to 2012, reported that 16% of patients experienced postoperative renal dysfunction. Of these, 83% were classified as “at risk” and 3% as experiencing “injury” or “failure.” Notably, 47% of the affected patients recovered normal kidney function after surgery. Although biochemical changes in postoperative renal function were relatively common, most patients remained in the at-risk category and did not develop clinically significant dysfunction. Changes in estimated glomerular filtration rate (eGFR) were generally temporary, with 45% of patients showing recovery by discharge. Among patients with persistent biochemical alterations, 94% had mild-to-moderate kidney impairment (eGFR: 30–89 mL/min). Clinically significant postoperative acute kidney injury (AKI) was rare (<1% of patients) and transient, resolving shortly after surgery in half of these cases. The study also revealed that postoperative renal dysfunction was more frequent in older patients, likely due to reduced renal mass. However, the study did not explore the underlying causes or mechanisms of postoperative renal dysfunction, highlighting the need for further research. ²⁶ In 2021, a prospective observational study by Wisén et al. ²⁷ involving 18 participants reported that AKI is among the most common adverse events after major surgery and is associated with increased morbidity, mortality, and prolonged hospital stays. The study observed a significant rise in serum creatinine 3 h after liver resection; early transient AKI occurred in four patients postoperatively, and one patient developed AKI on the fifth postoperative day. Approximately 28% of patients experienced postoperative AKI with continuous increases in serum creatinine, although urine N-acetyl-β-D-glucosaminidase (NAG), a marker of tubular injury, remained unaffected. Limitations included the small sample size, absence of awake baseline samples prior to anesthesia induction, and lack of a control group for comparison. ²⁷ In 2023, Kuang et al. ²⁸ developed a risk model to predict postoperative AKI in patients undergoing LCVP hepatectomy. This prospective cohort study included 1949 patients, who were divided into AKI and non-AKI groups with one-to-one matching. The study identified the lowest intraoperative systolic blood pressure, norepinephrine usage, furosemide administration, and surgery duration as independent risk factors for postoperative AKI. LCVP anesthesia relies on maintaining a state of reduced circulating blood volume, and the use of vasodilators not only lowers CVP but also alters blood flow distribution. However, fluid restriction and hypotension associated with LCVP may reduce renal perfusion pressure, and the impact of LCVP on renal function remains controversial. ²⁸ In the same year, Erkoç et al. ²⁹ studied living donor liver surgeries and reported that among 130 liver donor resections, only 4 patients undergoing right hepatectomy developed stage I AKI within the first 24 h (3.1%), all of whom recovered within 48 h postoperatively. The study suggested that simple fluid management targeting CVP <5 mmHg along with high pulse pressure variation (PPV) or stroke volume variation (SVV) may not induce AKI in living liver donors. Although maintenance of CVP ≤5 mmHg is commonly employed to reduce blood loss during hepatectomy, its use in living liver donors remains controversial. ²⁹ Over time, new renal function monitoring indicators have emerged; however, the underlying mechanisms linking LCVP to renal outcomes remain unclear. Therefore, future research should investigate the mechanisms of renal injury following LCVP hepatectomy to develop effective preventive and therapeutic strategies. ²⁹ Epidural analgesia combined with general intravenous anesthesia is widely used in major surgeries, including hepatectomy. In a 2015 study by Kambakamba et al. ³⁰ involving 1153 patients, 8.2% developed postoperative AKI, which was associated with increased morbidity and mortality. The incidence of AKI was significantly higher in patients receiving epidural analgesia (EDA). Although no significant difference was observed in AKI incidence for minor hepatectomies with or without EDA, a significant increase was observed in patients undergoing major hepatectomies. These findings suggest that EDA may be a risk factor for postoperative AKI in hepatectomy. ³⁰

Brain

The concept of cerebral autoregulation (CA), first described by Lassen, ³¹ is essential for protecting the brain—one of the body’s most vital organs—from injury. CA enables cerebral blood flow (CBF) to remain relatively stable across a wide range of blood pressures (BP), typically between a MAP of 50 and 150 mmHg. This concept has evolved into what is now referred to as “static cerebral autoregulation (sCA),” which reflects the steady-state relationship between CBF and BP.^32,33 The term “static” denotes changes in CBF (or velocity) in response to significant MAP alterations once a stable hemodynamic state has been achieved.

However, in liver resection surgery, despite efforts by surgeons and anesthesiologists to maintain hemodynamic stability, fluctuations in blood pressure are common due to the liver’s complex anatomy and the technical difficulty of the procedure. It remains unclear whether the brain receives adequate perfusion during these fluctuations, and if not, whether this affects the speed of postoperative awakening or has short- and long-term impacts on neurocognitive function. A cohort study by Li et al. ³⁴ (2017) found that patients managed with LCVP had lower serum S-100 calcium-binding protein (S100β) levels and higher Mini-Mental State Examination (MMSE) scores at certain postoperative time points compared with a conventional management group. These effects may be related to reduced inflammatory responses from decreased blood loss and transfusions, shorter surgery duration, lower psychological stress, or other mechanisms. The study suggests that intraoperative LCVP management may improve postoperative cognitive function, particularly in elderly patients. However, the study was limited by a small sample size and a short postoperative follow-up, assessing only early cognitive function after hepatectomy. ³⁴ In late 2023, Lv et al. ³⁵ conducted a prospective randomized controlled trial with 80 participants to evaluate the effects of targeted mild hypercapnia (TMH) versus normocapnia on cerebral oxygen saturation in patients undergoing laparoscopic hepatectomy under LCVP. Patients were assigned to either the TMH or normocapnia group. Both groups experienced declines in MAP and regional cerebral oxygen saturation (rSO₂) during surgery; however, but normocapnia group experienced more pronounced reductions in left and right rSO₂ relative to preoperative values, whereas the TMH group maintained stable rSO₂. No significant difference in the incidence of postoperative delirium at 24 h was observed between the groups. The study’s small sample size may limit the reliability of the findings. Moreover, it focused solely on the impact of LCVP on cerebral oxygenation without a comprehensive evaluation of other intraoperative parameters or postoperative outcomes. Long-term follow-up was not performed, so the prolonged effects of LCVP on postoperative outcomes remain unknown. ³⁵ Although the association between decreased cerebral oxygen saturation and postoperative delirium is still debated, sustained low rSO₂ is clearly undesirable for surgeons and anesthesiologists.^36,37 Research on perioperative brain function during LCVP hepatectomy remains limited. Similar to the heart, liver, and kidneys, the brain is highly susceptible to ischemic and reperfusion injuries, yet few studies have addressed this area. With the increasing availability of invasive and noninvasive brain function monitoring tools in clinical practice, future studies are needed to clarify cerebral functional changes during LCVP hepatectomy and to explore the underlying mechanisms.

Heart

A prospective observational study by Wisén et al. ²⁷ (2021), including 18 participants, indicated that elevated high-sensitivity troponin T (hs-TnT) levels can predict mortality and cardiovascular complications after non-cardiac surgery, independent of overt signs of myocardial ischemia. In this cohort, 28% of patients exhibited pathological troponin values, highlighting that hepatectomy is a high-risk procedure with potential cardiac complications. Five patients (28%) had elevated baseline hs-TnT levels (>14 ng/L), and four out of these five experienced postoperative myocardial injury, defined as an increase in hs-TnT >5 ng/L from baseline. However, the study did not systematically evaluate signs of acute myocardial ischemia, such as postoperative ST-segment changes, development of Q waves, chest pain, echocardiographic evidence of wall motion abnormalities, new myocardial viability loss, or coronary thrombosis confirmed by coronary angiography. These findings underscore the potential cardiac risks associated with hepatectomy. The presence of elevated hs-TnT levels in a notable proportion of patients emphasizes the need for careful perioperative cardiac monitoring. The absence of systematic evaluation for acute myocardial ischemia highlights the importance of comprehensive cardiovascular evaluation in patients undergoing high-risk procedures, particularly those with elevated baseline hs-TnT levels. Focusing on hs-TnT as a predictor of postoperative cardiac events provides valuable insight for perioperative care. However, the study’s small sample size and lack of systematic ischemia assessments indicate that further research with larger cohorts and more detailed cardiac evaluations is required to better characterize cardiac risks and to develop appropriate monitoring and intervention strategies for hepatectomy patients. ²⁷

Gastrointestinal tract

A prospective observational study by Wisén et al. ²⁷ (2021), including 18 participants, investigated intestinal mucosal injury during liver surgery using two biomarkers: intestinal fatty acid-binding protein (I-FABP) and D-lactate. I-FABP, released by intestinal epithelial cells, serves as an early marker of epithelial cell death, while D-lactate, produced by bacterial fermentation, indicates compromised mucosal integrity when detected in circulation. The combination of these markers allows sensitive detection of intestinal mucosal injury during liver surgery. ²⁷ The study observed a continuous postoperative increase in I-FABP, with a maximum rise of 75% at 3 h after surgery. D-lactate was not detected at any time point, suggesting that although intestinal epithelial cells were affected, the intestinal endothelium remained intact, and the intestinal barrier was preserved. These findings indicate transient injury to intestinal epithelial cells. However, as a preliminary observational study, the results require validation in larger patient cohorts to determine whether intestinal function is truly impaired. The absence of D-lactate despite the observed increase in I-FABP indicates that the injury was confined to the epithelial layer, without compromising the overall integrity of the intestinal barrier. This distinction is important for understanding the extent of intestinal injury during liver surgery and for guiding postoperative management to prevent or mitigate complications related to intestinal dysfunction. Further studies with larger patient cohorts are needed to clarify the clinical significance of these findings and to determine the potential impact on overall intestinal function in the context of liver surgery.

Internal environment

Case reports by Zou et al. ³⁸ (2015) highlighted that perioperative lactic acidosis is a rare but important consideration. The CLCVP technique, with its multiple advantages, is widely applied in hepatectomy. However, most studies on CLCVP involve relatively short surgical durations, resulting in limited periods of CLCVP and hepatic vascular occlusion (HVO). These case reports raised concerns that for longer surgeries—particularly those with extended liver parenchymal transection—the benefits and risks of CLCVP should be carefully reassessed. Prolonged hypovolemia can be harmful, potentially causing severe intraoperative acidosis due to disturbances in the internal environment and negatively affecting postoperative organ function. Management of metabolic acidosis, including lactic acidosis, can be challenging. Zou et al. suggested that when pH drops significantly or adverse reactions occur, administration of sodium bicarbonate should be considered. This recommendation is especially pertinent in cases where prolonged surgical times combined with CLCVP result in substantial lactic acid accumulation and acidosis. These case reports emphasize the importance of careful monitoring and management of acid–base balance during prolonged liver surgeries, particularly when employing techniques such as CLCVP and HVO. They also highlight the potential drawbacks of these methods, including the risk of acidosis, and the need for strategies to manage such complications. Recognizing and addressing these risks is essential for optimizing patient outcomes and minimizing perioperative complications in complex hepatectomy procedures. ³⁸

Hematological system

A 2013 study by Barton investigated perioperative coagulation changes in patients undergoing hepatectomy using both standard coagulation tests—prothrombin time-international normalized ratio (PT-INR), activated partial thromboplastin time (APTT), platelet count, and fibrinogen levels—and thromboelastography (TEG). The study found that following hepatectomy, PT-INR values increased, APTT decreased, fibrinogen levels declined, and platelet counts were reduced, indicating alterations in coagulation parameters. However, TEG results suggested that overall coagulation function remained largely stable. These findings highlight that although traditional coagulation tests detect abnormalities after hepatectomy, global hemostatic function may remain preserved. However, the study had several limitations. The sample size was relatively small, and it included only post-hepatectomy patients without a comparative control group. Additionally, clinical outcomes such as thrombosis and bleeding were not thoroughly examined. Although the study highlighted the presence of coagulation abnormalities, it remains unclear whether these findings warrant overdiagnosis or overtreatment. Barton and colleagues contributed valuable insights into coagulation changes following hepatectomy, but their work underscores the need for more comprehensive research. Future studies should involve larger patient cohorts with appropriate control groups and include detailed analyses of clinical outcomes to establish optimal strategies for diagnosing and managing coagulation dysfunction in this population. ³⁹

Future perspectives

A common limitation across the studies reviewed is the small sample size, which may introduce selection bias and limit the generalizability of the findings. Furthermore, there is a notable lack of comprehensive research exploring the mechanisms underlying organ function injury. To address these gaps, future studies should involve larger cohorts and, ideally, multicenter clinical trials to reduce bias and improve external validity. In addition, increased research focus on elucidating the mechanisms of organ injury across different medical contexts is needed to inform more effective prevention and management strategies.

During the LCVP period, the MAP can fall below 65 mmHg, reducing organ perfusion and potentially causing ischemia and reperfusion injury. Conventional renal and hepatic function tests may lack the sensitivity to detect mild ischemic or reperfusion-related damage. Consequently, there is a need to identify more sensitive and specific biomarkers that accurately reflect organ injury. Future research should focus on identifying and validating such biomarkers and evaluating their clinical utility, particularly in surgeries involving LCVP techniques. Addressing these challenges will require coordinated efforts from the medical research community, emphasizing large-scale, well-designed studies that can provide definitive evidence and inform clinical practice. Such research will deepen the understanding of the complex interplay between surgical techniques, organ function, and patient outcomes in procedures such as hepatectomy, ultimately enhancing patient care and safety. ⁵

In 2011, Guo et al. ⁴⁰ conducted animal experiments and demonstrated that bleeding during hepatectomy is almost linearly related to CVP; lower CVP corresponds to reduced blood loss. Significant differences were observed in CO, cardiac index (CI), and oxygen delivery (DO₂) between groups with CVP <2 cm H₂O and CVP ≥2 cm H₂O. Hemodynamic instability occurred when CVP fell below 2 cm H₂O, with marked reductions in CO and ventricular filling pressure. These findings indicated that an optimal CVP of 2–3 cm H₂O in a pig model undergoing LCVP hepatectomy minimizes blood loss while maintaining stable hemodynamic and oxygen metabolism. ⁴⁰ The 2013 study by Lin et al. ²¹ further advanced the understanding of CLCVP during hepatectomy, particularly in patients with HCC undergoing partial liver resection. Maintaining CVP between 2.1 and 3 mmHg during liver transection significantly reduced blood loss and had a substantially lower adverse effect on tissue perfusion compared with CVP <2 mmHg. The study also noted that most patients could maintain a systolic blood pressure ≥90 mmHg when CVP remained above 3 mmHg. These findings highlight the importance of balancing blood loss reduction with adequate organ perfusion, providing a precise CVP guideline for anesthesiologists and surgeons to optimize patient outcomes. ²¹ As liver surgery continues to advance with new techniques and a deeper understanding of perioperative management, guidelines for optimal CLCVP range will require ongoing updates. The development of novel methods to control LCVP underscores the dynamic nature of surgical practice. Anesthesiologists and surgeons are continually refining their approaches to hepatectomy, making regular review and revision of clinical protocols essential to minimize impacts on vital organ function. Continued research and well-designed clinical trials are therefore critical to maintain these guidelines updated, evidence-based, and effective in enhancing patient safety and improving surgical outcomes in hepatectomy procedures.

Limitations

Current literature lacks studies examining the effects of LCVP duration on physiological responses, which likely vary depending on the length of surgery. The duration of LCVP maintenance may influence the body’s ability to tolerate hypovolemia, particularly during prolonged procedures. Future research should compare LCVP strategies in short (e.g. 1 h) versus long (e.g. 10 h) surgeries to better understand physiological effects and inform personalized surgical approaches. Although this study did not specifically address LCVP duration, it represents an important area for future investigation.

Additionally, laparoscopic and open surgeries may differ in their physiological responses to low CVP. Differences in mechanisms such as pneumoperitoneum in laparoscopic surgery that affect VR or larger incisions in open surgery impacting hemodynamics suggest that LCVP may have variable effects depending on surgical approach. Future studies should evaluate these differences to optimize LCVP management across diverse surgical settings.

In liver resection studies, the extent of surgery—such as limited versus major resection—represents a potential confounding factor that may affect clinical outcomes. Most existing studies focus on outcomes within a single surgical approaches without directly comparing different extents of resection. This limits the ability to evaluate how surgical extent influences patient outcomes. Although cross-comparisons are rare in the current literature, differences between limited resections and major procedures, such as associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) or extended hepatectomy, could be clinically significant. Future research should incorporate comparative analyses across varying resection extents to more comprehensively evaluate their impact on survival, postoperative recovery, and complication rates.

In summary, although this study advances the understanding of the effects of LCVP, several limitations persist. The absence of data on the duration of LCVP maintenance precludes a detailed assessment of how surgery length influences its efficacy. Moreover, differences in physiological responses between laparoscopic and open surgeries remain underexplored, limiting comparisons of LCVP effects across surgical approaches. Future research should aim to address these gaps by evaluating the impact of both surgery duration and type on LCVP outcomes.

Conclusions

In summary, the LCVP technique has been widely adopted in liver surgery for its ability to improve surgical field visibility, reduce intraoperative blood loss and transfusion requirements, and support better patient outcomes. Nevertheless, maintaining stable vital signs during LCVP presents significant challenges for anesthesiologists. Although the technique’s benefits have led to its rapid adoption, its limitations must be acknowledged. Increasing attention has been directed toward postoperative organ function recovery and enhanced intraoperative monitoring during LCVP-assisted liver resection. Ongoing research and interdisciplinary collaboration are expected to further optimize LCVP management, enhancing the safety and efficacy of liver resection procedures.

Figure 1.

Methods to maintain low CVP during liver surgery.