Renal implications of pneumoperitoneum in laparoscopic surgery: mechanisms, risk factors, and preventive strategies

Article information

Korean J Anesthesiol. 2024;77(6):575-586

Publication date (electronic) : 2024 April 26

doi : https://doi.org/10.4097/kja.24011

Gianluca Villa^1,2, Marco Fiorentino³, Eleonora Cappellini¹, Sergio Lassola⁴, Silvia De Rosa^,4,5

¹Department of Health Sciences, Anesthesiology Intensive Care and Pain Medicine, University of Florence, Florence, Italy

²Department of Anesthesia and Intensive Care, Oncological Anesthesia and Intensive Care, AOU Careggi, Florence, Italy

³Department of Precision and Regenerative Medicine and Ionian Area, Nephrology Unit, University of Bari, Italy

⁴Anesthesia and Intensive Care, Santa Chiara Regional Hospital, APSS Trento, Italy

⁵Center for Medical Sciences - CISMed, University of Trento, Trento, Italy

Corresponding author: Silvia De Rosa, M.D. Center for Medical Sciences – CISMed, The University of Trento, Via S. Maria Maddalena 1, 38122 Trento, Italy Tel: +39-3933098583 Fax: +0557946211 Email: derosa.silvia@gmail.com; silvia.derosa@unitn.it

Received 2024 February 8; Revised 2024 April 9; Accepted 2024 April 12.

Abstract

Introduction

Pneumoperitoneum, which is established for laparoscopic surgery, has a systemic impact on the renal system and may contribute to acute kidney injury (AKI) or postoperative renal dysfunction. Specifically, when the pressure exceeds 10 mmHg, pneumoperitoneum can result in reduced renal blood flow, renal dysfunction, and transient oliguria. The mechanisms underlying the renal effects of pneumoperitoneum include both the direct effects of elevated intra-abdominal pressure (IAP) and indirect factors such as carbon dioxide (CO₂) absorption, neuroendocrine influences, and tissue damage secondary to oxidative stress. As patients with preexisting renal dysfunction may experience further deterioration due to pneumoperitoneum, preserving the function of the remaining kidney is crucial in procedures such as laparoscopic live-donor nephrectomy.

Despite extensive research, the mechanisms underlying the renal effects of pneumoperitoneum have not been fully elucidated. Available evidence of its effects on renal function is limited and of moderate quality [1]. Although the adverse effects of pneumoperitoneum on serum creatinine (sCr) levels, renal blood flow, and urine output (UO) are apparent, the reliability and clinical relevance of these findings are not well understood, as the long-term effects of pneumoperitoneum have not been assessed [2].

This review aims to delve into the pathophysiological hypothesis of kidney damage, mechanisms leading to oliguria and kidney damage, and fluid management in surgical patients during pneumoperitoneum.

Epidemiology of AKI for laparoscopic procedures

The incidence of AKI varies considerably, ranging from 0.8% to 22.4% after abdominal surgery [3–6] and from 3.4% to 8.8 % after laparoscopic surgery [7–13]. This variability stems from differences in AKI diagnostic criteria, study designs, and patient characteristics, which collectively influence the reported incidence rates and complicate comparisons between studies. The adoption of the Kidney Disease Improving Global Outcomes (KDIGO) criteria [14] has notably affected AKI incidence rates. Studies applying the KDIGO criteria often report higher incidences of postoperative AKI due to its greater sensitivity, which is attributed to the minimal change in sCr required for diagnosis. For instance, in two cohorts of similar patients undergoing laparoscopic abdominal surgery, Sim et al. [7] and Abdullah et al. [8] reported postoperative AKI incidences of 8.8% and 2.9%, respectively, using the KDIGO definition and its modified version. The KDIGO criteria has been found to be inconsistent with other diagnostic criteria, such as the Risk, Injury, Failure, Loss of kidney function, and End-stage kidney disease (RIFLE) or the Acute Kidney Injury Network (AKIN) definitions.

Furthermore, the approach to AKI diagnosis, whether prospective or retrospective, significantly influences the reported incidence rates. The prospective inclusion of both UO and sCr criteria, as per the KDIGO definition, has resulted in higher incidence of AKI than retrospective assessments based on creatinine assessments over time [9–11]. For instance, Srisawat et al. [9] reported an AKI incidence of 35% using the KDIGO criteria in a single-center prospective study, whereas retrospective studies adopting the same criteria reported lower incidences ranging from 3.9% [10] to 9.9% [11], despite enrolling comparable patient cohorts. Moreover, studies focusing solely on sCr for AKI definition have reported even lower incidences of postoperative AKI, such as the 3.4% and 1.6% reported by Park et al. [12] and Moon et al., [13] respectively. These retrospective studies included patients with a high risk of AKI, including those undergoing laparoscopic pancreaticoduodenectomy and liver resection.

Direct effect of CO₂

Carbon dioxide (CO₂), which was introduced to establish pneumoperitoneum in the 1920s, is the most suitable gas for insufflation into the abdominal cavity (pneumoperitoneum of 8–20 mmHg) [15]. Although CO₂ is non-toxic and non-flammable, its high solubility in blood and tissues, easy elimination through the lungs, and cost-effectiveness make it an optimal choice [16,17]. Direct and indirect physiological changes in the kidneys are associated with CO₂ insufflation, which activates significant mechanical and neurohumoral mechanisms. Regional perfusion of the kidneys occurs in four structurally distinct vascular zones: the cortex, outer stripe of the medulla, inner stripe of the outer medulla, and inner medulla [18]. A pressure of 20 mmHg during insufflation causes a 60% decrease in the renal blood flow, leading to a blood shift from the outer cortex to the juxtamedullary zone. This shift adversely affects filtration because the majority of the glomeruli are located in the cortex [18]. Both robotic and laparoscopic procedures result in a 20%–40% decrease in the glomerular filtration rate (GFR) and a 60%–80% decrease in UO when the pressure exceeds 10 mmHg, as demonstrated in experimental and clinical studies. Fig. 1 illustrates the renal effects of CO₂ pneumoperitoneum. In a systematic review and meta-analysis of animal studies, Wever et al. [2] found robust evidence of harmful effects on renal function and perfusion during pneumoperitoneum; however, data on long-term effects are limited. Another systematic review by Demyttenaere et al. [19] found a transitory reduction in renal blood flow in 17 of the 20 examined studies. Factors such as insufflation pressure, patient positioning (worse in the head-up position), and fluid status were identified as significant contributors to decreased renal blood flow. Long-term effects indicated that sCr normalized 24 h after pneumoperitoneum insufflation at 15 mmHg. Bilgic et al. [20] found a correlation between increased levels of KIM-1 and creatinine, which is consistent with histopathological analyses. Additionally, the IAP was found to significantly increase the degree of kidney injury, even when KIM-1 levels were not significantly increased.

Fig. 1.

Neuroendocrine and renal effects of pneumoperitoneum. These figures outline neuroendocrine responses (e.g., sympathetic activation and hormonal fluctuations) and renal changes (e.g., reduced blood flow and altered filtration rates) during pneumoperitoneum. These effects underscore the physiological effects of laparoscopic surgery on the neuroendocrine and renal systems and reflect potential clinical implications. NSAID: non-steroidal anti-inflammatory drug, RBF: renal blood flow.

Pathophysiological hypothesis of kidney damage

The pathophysiological hypothesis of kidney damage in surgical patients, particularly those undergoing laparoscopic procedures, encompasses various mechanisms, including renal hypoperfusion, cellular hypoxia, inflammation, and direct toxicity.

The primary mechanism of tubular epithelial cell injury during kidney hypoperfusion involves a mismatch between oxygen and nutrient supplies and the metabolic demand of renal cells. A reduction in the mean arterial pressure (MAP) is a significant cause of decreased renal perfusion pressure, similar to the effect occurring during pneumoperitoneum. Specifically, the pressure applied to the renal parenchyma due to pneumoperitoneum results in reduced renal blood flow [21]. Locally regulated activation of myogenic-induced vasodilation may ensure a transient increase in renal blood flow in patients with physiological renal functional reserve (RFR), thereby maintaining a normal GFR range [22]. Elderly patients with multiple comorbidities, often undergoing laparoscopic surgery, have a limited RFR, making them prone to intraoperative insult to the kidney (Fig. 2). Persistent insults to the kidney can lead to tubular apoptosis, necrosis, and electrolyte imbalance and electrolyte and water homeostasis impairments are associated with reduced waste product elimination [21]. Postoperative AKI is thus typically diagnosed. Prolonged reduction in renal perfusion pressure [19] during pneumoperitoneum in patients with impaired myogenic adaptive mechanisms may further contribute to ischemic reperfusion insults (Fig. 2) [23]. This, in turn, triggers a dysregulated inflammatory response [24], including the activation of neutrophils (as well as macrophages and natural killer, T, and B cells) [25] and the release of reactive oxygen species (ROS) or other inflammatory mediators that promote endothelial cell injury and swelling [26,27].

Fig. 2.

Pathophysiology of kidney damage during laparoscopic surgery. ADH: antidiuretic hormone.

Patients undergoing laparoscopic or robot-assisted surgery may also experience additional nephrotoxic injuries, including exposure to certain intraoperative agents, promotion of renal vasoconstriction, and direct proximal tubule cytotoxicity (Fig. 2) [28].

Inflammation-derived damage and metabolic abnormalities contribute significantly to kidney damage triggered by proinflammatory molecules [29,30] during pneumoperitoneum-induced AKI [31]. Notably, the kidneys require a large amount of energy from adenosine triphosphate for active water and solute transport, which is facilitated by its extensive mitochondrial presence [32]. Disruption of physiological proton pumping across the inner mitochondrial membrane can lead to subsequent mitochondrial dysfunction, exacerbating cell damage through the production of ROS and the release of pro-apoptotic or proinflammatory factors, such as mitochondrial DNA (Fig. 2) [33].

Oliguria can develop irrespective of the gas type used for insufflation. An ideal insufflation gas should be cost-effective, colorless, non-flammable, non-explosive, easily eliminated, and non-toxic. CO₂ is a remarkably soluble gas, with a solubility coefficient of 0.570, and is absorbed by the peritoneum, delivered directly to the lungs through circulation, and excreted by the lungs during respiratory exchange [34]. However, CO₂ is not a perfect gas and its absorption can lead to hypercapnia and acidosis, necessitating counteractive hyperventilation [15]. CO₂ is also associated with an increase in the MAP, and in cases of high blood concentrations, it can result in cardiac toxicity. Although the direct effects of CO₂ pneumoperitoneum on renal blood flow have been considered, CO₂-related cardiovascular effects may indirectly affect renal function.

Several gases (e.g., helium, argon, nitrogen, nitrous oxide, and room air) have been introduced as alternatives to carbon dioxide for establishing pneumoperitoneum [35]; however, their use remains controversial. Helium and argon are inert gases but are less soluble than CO₂, potentially increasing the risk of venous gas embolism [36]. Nitrous oxide (i.e., laughing gas) is a mild anesthetic with analgesic properties [35]. However, two cases of explosions using electrocautery during laparoscopy have been reported [37]. Recently, Yu et al. [38] reported no severe side effects related to the use of CO₂, nitrous oxide, or room air, although severe side effects do occur rarely. The effects of nitrous oxide and helium pneumoperitoneum are not well understood compared with those of CO₂ pneumoperitoneum. Evidence from one trial with a small sample size suggested that room-air pneumoperitoneum may decrease hospital costs for patients undergoing laparoscopic abdominal surgery. The safety of nitrous oxide, helium, and room-air pneumoperitoneum is yet to be established.

Conversely, compared to open procedures, robotic and laparoscopic surgeries offer reduced postoperative pain as they do not suppress the immune system as significantly [39]. They also exhibit a lower elevation of proinflammatory cytokines, such as interleukin-6 (IL-6), IL-1, and tumor necrosis factor-alpha (TNF-α), along with decreased C-reactive protein levels.

Although CO₂ pneumoperitoneum induces a lower release of IL-6 compared to room air, TNF-α levels may vary depending on pneumoperitoneum pressure [40]. Higher plasma TNF-α levels were found in rats undergoing a pneumoperitoneum pressure of 10 mmHg than in those undergoing a pressure of 6 mmHg and control groups [41]. Surgery causes an immediate elevation of stress hormone levels and decreases the immune response [42]. A systemic stress response related to pneumoperitoneum is evoked by an increase in IAP from baseline to 20 mmHg [43]. Remarkably, an increase in IAP increases plasma epinephrine and norepinephrine levels and does not depend on the type of gas used [44]. However, in the open surgical approach, adrenocortical hormone, cortisol, norepinephrine, epinephrine, insulin, and blood sugar levels increase and remain elevated during the first 24 h postoperatively [45].

Conversely, in pneumoperitoneum, elevated levels of vasopressin or antidiuretic hormone (ADH) are associated with an increase in systemic vascular resistance [46]. However, intra-abdominal pH changes secondary to pneumoperitoneum can stimulate the activation of peritoneal nerve endings, leading to intra-abdominal pH changes and release of vasopressin via the neurogenic vagal pathway [47]. In addition, decreased venous return stimulates right atrial volume receptors, triggering the release of vasopressin/ADH. This results in decreased UO, although fluid replacement increases the risk of fluid overload [48]. The systemic stress response resolves in the immediate postoperative period, after pneumoperitoneum resolution (Fig. 1).

Risk factors for AKI during pneumoperitoneum

Risk factors for AKI during pneumoperitoneum in minimally invasive surgery include CO₂ insufflation and elevated IAP. While the kidneys are susceptible to pressure changes, risk factors such as dehydration, older age, and pre-existing chronic kidney disease (CKD) affect the RFR [49]. However, assessing changes in renal function during laparoscopic procedures is challenging because no specific markers for monitoring rapid changes in GFR in clinical practice are known. Both pre-clinical and clinical studies have shown transient worsening of renal function with oliguria and reduced GFR (5). Preexisting CKD is a crucial risk factor for AKI in pneumoperitoneum. Cisek et al. [50] investigated the changes in renal function during and after pneumoperitoneum in a swine model with reduced renal mass, suggesting that pneumoperitoneum had an impact on the onset of AKI, with no identified long-term consequences. Abboud et al. [51] found a direct correlation between IAP elevation and AKI development, particularly in diabetic rats, which are sensitive to the deleterious effects of pneumoperitoneum. A case report demonstrated progression to end-stage renal disease in a patient with preexisting CKD after laparoscopic surgery. Moreover, renin-angiotensin-aldosterone system inhibitors pose another risk factor as they affect hemodynamic changes during laparoscopic procedures [52]. Lindstrom et al. [53] reported oliguria and a reduced GFR in rats treated with angiotensin-converting enzyme inhibitors, underscoring the need to discontinue such treatment during conditions characterized by elevated IAP to maintain adequate renal perfusion. Recently, the incidence of postoperative AKI between laparoscopic and open surgery in patients with colorectal cancer has been investigated, with no significant differences in such outcomes reported. At the same time, ICU admission, length of hospital stay, and 1-year mortality were better in the laparoscopic group. Additionally, the same report highlighted that a high body mass index (BMI), preoperative hypoalbuminemia, history of diabetes mellitus, and hypertension were significantly associated with the onset of postoperative AKI. Table 1 summarizes the risk factors and bundles for AKI. The use of validated risk scores for postoperative AKI is suggested to better stratify patients and facilitate the application of interventions targeting specific modifiable risk factors.

Table 1.

Risk Factors and Bundles for Acute Kidney Injury

Diagnosis of acute kidney injury

Prevention of AKI

Preventing AKI is paramount in laparoscopic surgery, and KDIGO bundles have been shown to be essential [55]. Despite it being minimally invasive, laparoscopic surgery introduces challenges such as pneumoperitoneum and nephrotoxic agents. The application of the KDIGO bundle is a potent strategy for mitigating the risk of AKI [55,79]. Preoperative assessment of AKI risk factors, including age, renal conditions, diabetes, and hypertension, is crucial for tailoring prevention strategies. The KDIGO bundle targets potential AKI triggers and emphasizes the need for hemodynamic support for adequate renal perfusion. Maintaining optimal fluid balance, a key component of the bundle, is vital in laparoscopic surgery, balancing hydration and avoiding fluid overload amidst pneumoperitoneum [80]. Renal dysfunction may occur in the context of restrictive fluid administration (with consequent hypotension and renal hypoperfusion) or more liberal fluid approaches (with consequent pulmonary and organ congestion) [81]. Choosing an appropriate fluid solution is crucial, as recent evidence suggests an association between certain solutions and increased risk of AKI [82,83].

Additionally, careful consideration of medications and contrast agents is necessary to avoid nephrotoxic agents whenever possible and to closely monitor sCr levels and UO postoperatively to detect AKI early [84]. The KDIGO bundle recommends avoiding nephrotoxic agents whenever possible, opting for alternatives or adjusting dosages. The use of bicarbonate or N-acetylcysteine is not supported by strong clinical evidence, and preventive measures continue to be based on hydration therapy [85]. Close monitoring of sCr levels and UO in the postoperative phase is indispensable for early detection of AKI. Furthermore, the use of other potential nephrotoxic drugs should be considered to avoid further insults to renal function [79]. The adequate use of antibiotic treatment and the judicious use of pain management techniques to encourage early mobilization further aid in reducing the risk of AKI. The recent introduction of urinary biomarkers such as TIMP-2 and IGFBP7 has enhanced the early detection and prevention of AKI. Additionally, the application of a biomarker-triggered KDIGO bundle has shown promising results in reducing the incidence of AKI in various surgical settings, emphasizing the importance of these biomarkers in guiding AKI prevention strategies [86–89].

Fluid therapy management plays a pivotal role in patients with AKI by balancing the preservation of intravascular volume and systemic hemodynamics while avoiding hemodilution and fluid overload. The timing and modalities of fluid management require careful consideration, especially in patients with impaired cardiac function, because fluid overload is associated with increased mortality and hinders renal recovery after AKI [90,91]. Individualizing fluid administration based on the patient’s condition and the phase of critical illness is crucial, considering factors such as diuretic resistance and the multifactorial nature of AKI [92,93]. Oliguric patients may not respond adequately to fluid therapy despite improvements in systemic hemodynamic parameters, suggesting a dissociation between systemic and renal hemodynamics [94]. Although fluid administration is the first-line treatment for hypotensive conditions during surgery, it may promote hemodilution, induce anemia, and reduce oxygen-carrying capacity. Hemodilution after fluid administration decreases blood viscosity, leading to modifications in capillary density and resulting in reduced oxygen transport at the tissue level [21]. These changes may reduce renal perfusion and consequently lead to renal hypoxia and AKI, even after optimizing the cardiac output [95]. Several studies have shown that fluid administration significantly improves organ perfusion in patients with microcirculatory dysfunction at baseline, but not in those with normal organ perfusion despite normalization of systemic hemodynamic parameters and cardiac output [96]. In this scenario, the use of specific tools to evaluate microcirculation and tissue oxygen delivery, such as functional capillary density, capillary hematocrit, and red blood cell velocity, may enhance our ability to assess which patients will benefit from fluid administration [97]. In this context, fluid administration should be individualized for each patient based on their condition and the phase of critical illness.

Conclusion

In surgical procedures involving pneumoperitoneum, compromised renal function results from complex pathophysiological mechanisms, including induced abdominal hypertension, varying CO₂ levels, and neuroendocrine activation. These in turn diminish intraoperative renal perfusion, which may not adequately correlate with the loss of renal autoregulation. Future research should focus on elucidating the specific pathophysiological mechanisms and exploring the utility of biomarkers. Such efforts are essential for developing a comprehensive care bundle tailored to preventing renal function decline, particularly in individuals with a diminished RFR.

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