36. Renal Ramifications of CO 2 Pneumoperitoneum
Ayal M. Kaynan, M.D.
Sherry M. Wren, M.D.
The changes in renal physiology that occur during carbon dioxide insuffla- tion of the abdomen are complex and most likely include both mechanical and neurohumoral mechanisms. At times, these factors may together result in pro- found oliguria (urine output <0.5 mL/kg/hr), which may develop soon after insuf- flation and persist for several hours following surgery. Thus, it is incumbent upon the surgeon and anesthesiologist to recognize this fact so that an appropriate intraoperative fluid management plan can be devised and implemented. This chapter focuses on the direct and indirect renal effects of carbon dioxide pneu- moperitoneum, the mechanisms by which oliguria occurs, and a logical approach to fluid management in laparoscopic patients.
A. Direct Renal Effects of CO2 Pneumoperitoneum
Multiple animal and clinical studies have documented 20%–40% decreases in glomerular filtration rate (GFR) and a 60%–80% decrease in urine output during laparoscopic procedures carried out via CO2pneumoperitoneum [1–3].
These effects are most often noted when the intraabdominal pressure is above 10 mmHg [4] and are exacerbated by the reverse Trendelenburg position [5].
Diminished renal function is usually noted soon after insufflation and may persist for several hours following desufflation [3]. Ultimately, in otherwise healthy individuals, there is full recovery of renal function to preinsufflation levels [2, 6, 7] (Table 36.1).
Renal blood flow is also significantly affected by pneumoperitoneum. Mea- surements of renal blood flow during pneumoperitoneum in dogs have shown decreases of the order of 26% [2]. Elevation in the intraabdominal or renal venous pressure causes blood to shift from the outer cortex to the juxtamedullary zone [8]. The drop in renal cortical perfusion increases with increasing intraab- dominal pressures, such that at an insufflation pressure of 20 mmHg renal flow is decreased by as much as 60%. Filtration is thereby compromised because the majority of glomeruli reside in the cortex. To the extent that intraabdominal pres- sure is uniform in the abdomen, it is intuitive that intravascular pressure gradi- ents would favor centralization of blood flow to the larger vessels within the
juxtamedullary zone. The result of these alterations in renal perfusion are dimin- ished overall renal blood flow, glomerular filtration rate, and urine output.
Creatinine clearance is known to be decreased during CO2insufflation and for several hours afterward. Despite this, plasma creatinine levels usually nor- malize soon after desufflation [6]. Fortunately, histologic sections of kidneys taken both immediately following and long after CO2 pneumoperitoneum demonstrate no identifiable anatomic defects. This is true despite the fact that it has been demonstrated that pneumoperitoneum may result in elevations in the enzyme N-methyl-beta-D-glucosaminidase (NAG), a marker of proximal renal tubular cell damage. Thus, whatever toxic effect CO2pneumoperitoneum has upon normal renal parenchyma, the physiologic changes are transient and the long-term effects appear to be insignificant. In fact, there are no reports, to date, of pneumoperitoneum-induced renal failure in the setting of normal preopera- tive renal function.
What impact does the type of gas used for insufflation have on renal func- tion? There is evidence that oliguria develops regardless of the gas used to estab- lish pneumoperitoneum. CO2, however, has been associated with increased mean arterial pressure when compared to blood pressures observed with other gases such as N2O [9]. CO2pneumoperitoneum has also been associated with elevated systemic vascular resistance whereas the effect of N2O has been unclear. At very high blood concentrations, CO2can result in cardiac toxicity. Thus, in addition to the direct effects of CO2pneumoperitoneum on renal blood flow [decreased renal blood flow (RBF) and glomerular filtration rate (GFR)], CO2-related car- diovascular effects, via alterations in systemic blood pressure, vascular resis- tance, or cardiac output, may, indirectly, have an impact on renal function. The cardiovascular impact on renal function is discussed in greater detail below.
B. Purported Mechanisms for Oliguria
There are three putative explanations for pneumoperitoneum-induced olig- uria: (1) renal parenchymal compression and associated renal blood flow alter- ations, (2) cardiac output and arterial blood pressure alterations, and (3) central Table 36.1. Summary of renal effects of CO2pneumoperitoneum.
Increased Decreased
Antidiuretic hormone Renal blood flow
Renin Glomerular filtration rate (GFR)
Aldosterone Urine output
FEK FENa
Epinephrine Cardiac index
Endothelin
Systemic vascular resistance (SVR) Mean arterial pressure (MAP) FE, Fractional Excretion.
venous congestion. To test whether direct renal compression had any effect on renal function, canine renal parenchyma was compressed using a pressure cuff inflated to 15 mmHg in vivo, sparing involvement of the hilar vasculature, ureter, and contralateral kidney. For the treated kidney, glomerular filtration rate decreased 21%, estimated renal blood flow decreased 26%, and urine output decreased 63% [2]. In a similar study, rat kidneys were studied ex vivo in CO2
chambers pressurized to 15 mmHg. The renal hilar vasculature and ureters were catheterized and excluded from the pressurized chambers, thereby avoiding the potentially confounding direct effects of the CO2pneumoperitoneum on these structures. When the kidneys were perfused with blood/Ringer’s solution at 37°C in the CO2environment, significant oliguria was noted. Therefore, pneumoperi- toneum-related direct renal compression most likely contributes to the oliguria observed during laparoscopic cases. Further, when the blood pressure and inflow perfusion rate of the system were controlled, it was found that reduced intra- parenchymal cortical blood flow accounted for much of the reduction in urine output. Thus, increased pre- and postglomerular resistance were thought to be significant secondary factors [10].
The extent to which pneumoperitoneum-related cardiovascular alterations contribute to the development of oliguria is less certain and more controversial.
In the setting of CO2pneumoperitoneum, the main systemic hemodynamic sys- temic effects, as mentioned above, are increased systemic vascular resistance, increased mean arterial pressure, and decreased cardiac index [11]. Cardiac output may decrease by more than 10% as a result of increases in intraabdomi- nal pressure [12]. Hypercarbia, if it should ensue, may further impair cardiac function. A decrease in cardiac output in and of itself is a well-established phys- iologic cause for oliguria. Prolonged cardiac dysfunction and hypoperfusion can, of course, result in acute tubular necrosis and renal failure. In a canine study that assessed the effects of intraabdominal pressure at 0, 20, and 40 mmHg on cardiac output and renal function, it was found that renal blood flow and GRF were decreased. When compared to the measurements at 0 mmHg, an increase to 20 mmHg decreased both variables to less than 25% of control values. Increas- ing to a level of 40 mmHg decreased renal blood flow and GFR to 0 in some animals and 7% in the others. This was accompanied by a drop in cardiac output of 37% compared to dogs with 0 mmHg intraabdominal pressures. Expansion of volume via administration of the plasma expander dextran-40 corrected the drop in cardiac output but only restored the renal blood flow and GFR to 25% of the normal level. The measured renal vascular resistance increased 555% when the pressure was elevated from 0 to 20 mmHg in test subjects, suggesting the changes in renal blood flow and GFR are a local renal phenomenon, probably from renal compression, and are not as influenced by changes in cardiac output [4]. Thus, these results suggested that relatively small impairment in cardiac output is not a significant factor in the development of renal dysfunction seen with increased intraabdominal pressure in a euvolemic animal. Nevertheless, cardiac output is reduced with pneumoperitoneum, and it is difficult to ignore the associated deleterious renal effects.
Increasing the intraabdominal pressure via pneumoperitoneum increases the renal vein pressures via compression [13]. This increased pressure, in turn, results in a significant reduction in blood flow through this vessel [6]. Several investigators have examined the effects of pneumoperitoneum-induced renal
vein compression in greater detail. It has been demonstrated that unilateral renal vein compression decreases the glomerular filtration rate and urine output of both kidneys; of note, the effects are much more pronounced on the com- pressed side [1]. These results suggest that neurohumoral factors are also at play in addition to the more obvious compression-related decreased renal blood flow.
Therefore, venous compression may impair renal function via several different mechanisms.
Ureteral compression may also contribute to pneumoperitoneum-related oliguria; however, the available evidence does not support this position. Intra- venous pyelograms [6] and ultrasound examinations (personal experience) per- formed during laparoscopic procedures have not revealed hydronephrosis. It is conceivable that increased intraabdominal pressure may limit distension of the renal pelvis or that a longer period of ureteral compression is required before hydronephrosis becomes evident. However, ureteral catheterization, which should ensure that the ureter remains patent, has failed to mitigate oliguria during pneumoperitoneum [4]. To better define the effects of increased intraabdominal pressure on the ureter and renal function, selective ureteral compression studies need to be performed. At worst, ureteral compression is a minor contributor to pneumoperitoneum-related oliguria.
C. Neurohumoral Components
The very fact that oliguria persists after desufflation suggests that direct pres- sure-related renal effects do not fully account for the functional impairment that has been observed. Although direct compression could, in theory, result in tran- sient occult renal parenchymal injury that might account for early postoperative oliguria, it is likely that neurohumoral factors also play a role. Indeed, it has been shown that antidiuretic hormone (ADH) levels rise early during laparoscopic surgery and remain significantly elevated for at least 30 minutes to an hour after- ward [14, 15]. This finding is surprising if one considers that mean arterial pres- sure is elevated and sodium and water are retained during pneumoperitoneum.
However, the following pneumoperitoneum-related alterations might account for increased ADH release in this setting: decreased cardiac output, increased release of catecholamines, or increased renin production. Regardless of the cause, persistent ADH elevation immediately after release of the pneumoperi- toneum may explain, at least in part, the oliguria observed early after laparo- scopic surgery.
Other pneumoperitoneum-related humoral factors may also have profound effects on renal blood flow. The release of epinephrine, which causes vasocon- striction and reduces renal blood flow, has been shown to be increased during laparoscopic surgery [14, 16]. Endothelin, one of the most potent vasoconstric- tors known, is also released during pneumoperitoneum [1]. The use of nonse- lective endothelin antagonists has been shown to attenuate the surgery-related reduction in GFR by 35%; however, interestingly, oliguria persisted despite the better preserved GFR.
The documented activation of the renin-angiotensin-aldosterone system (RAAS) during laparoscopic procedures is another curious phenomenon. Renin
levels have been shown to increase up to 400% during CO2pneumoperitoneum [3, 17–19] and to return to baseline on desufflation [13]. Renin elevation in this setting may be the result of changes in intrarenal blood flow [20]. The typical electrolyte alterations associated with increased aldosterone levels have been noted during laparoscopic procedures carried out under CO2pneumoperitoneum:
hypernatremia, decreased fractional excretion of sodium, and increased frac- tional excretion of potassium [1]. The use of angiotensin-converting enzyme inhibitors, however, does not reverse pneumoperitoneum-related oliguria [13].
Activation of the RAAS, although not the primary cause of oliguria during laparoscopy, in all likelihood contributes to the decreased urine output observed during these procedures.
D. Exacerbating Risk Factors for Renal Dysfunction
Preexisting renal insufficiency must be considered when assessing the poten- tial impact of pneumoperitoneum on renal function. As mentioned previously, pneumoperitoneum is associated with elevation of the enzyme NAG (N-methyl- beta-D-glucosaminidase), which is a marker of proximal renal tubular damage.
Although histologic sections following pneumoperitoneum show no signs of necrosis, there is evidence to suggest that the kidneys undergo strain during laparoscopy [21]. In the living-related kidney donor literature, creatinine nadirs in recipients of laparoscopically harvested kidneys have been noted to be slightly higher than those observed in patients who received kidneys obtained via open methods. Despite this, graft survival and long-term creatinine levels are equiv- alent between the two groups [22]. In an animal study carried out to assess the fate of subjects with abnormal renal function, renal insufficiency was surgically induced, after which the animals were subjected to CO2pneumoperitoneum.
Transient florid renal failure resulted; however, with time, the renal function of the animals returned to baseline levels [23]. Thus, abdominal insufflation does cause more marked, albeit transient, renal dysfunction in those with preexisting renal disease.
Hemodynamic instability, a well-established cause of renal dysfunction and morbidity during and after open surgery, would be expected to exacerbate the renal effects of CO2pneumoperitoneum. Cardiac dysfunction from any cause (e.g., decreased venous return, CO2 toxicity, pneumothorax, pneumomedi- astinum) may result in reduced cardiac output and decreased renal blood flow.
In this setting, reductions in glomerular filtration rate and urine production may be predicted; in extreme cases, renal failure may ensue.
It has been suggested by some that aminoglycosides be avoided in patients undergoing laparoscopic surgery. It has been shown, however, that there is no synergistic toxicity associated with their administration in the setting of CO2
pneumoperitoneum [24].
E. Intraoperative Fluid Management
As for open surgery patients, the preoperative volume status of the patient must be taken into consideration when formulating a fluid management plan for a given patient who is to undergo a laparoscopic procedure. Most patients go into surgery a bit hypovolemic because they have taken nothing by mouth (NPO) for at least 8 hours. Patients who have completed a full mechanical bowel prepa- ration in anticipation of a large bowel resection, however, are usually much more dehydrated. It is important that the anesthetist adequately hydrate the patient before surgery such that the patient is euvolemic. The cardiovascular effects of pneumoperitoneum and anesthetic induction will be more dramatic in a hypov- olemic patient. Although 1–2 L isotonic fluid is all that is necessary to compen- sate for preoperative NPO status in most patients, patients who have undergone a mechanical bowel preparation usually require additional fluid.
In one study, moderate hydration with 500 mL fluid has been shown to improve cardiac index and reduce systemic vascular resistance when compared to the results of “nonhydrated” controls [13]. In experimental models of pneu- moperitoneum-related renal dysfunction, hypervolemia attained via the admin- istration of hypertonic fluids has been shown to reverse changes in renal blood flow and urine output. Interestingly, despite these improvements, impairment in creatinine clearance persists [25].
Having noted the importance of adequate hydration, it is a common mistake to overhydrate patients during laparoscopic surgery. Anesthesiologists often treat low intraoperative urine output with aggressive hydration because they wrongly attribute oliguria to hypovolemia. Likewise, anesthetists and surgeons often set the baseline I.V. rates based on the typical insensible losses incurred during an open procedure. In most instances, the insensible loss from abdominal insuffla- tion and mechanical ventilation during a laparoscopic case is less than the losses observed during a comparable open case. In one study, water vapor content fol- lowing dry gas insufflation was assessed; insignificant insensible water loss was demonstrated [26]. Although patients with normal cardiopulmonary function tol- erate the additional fluid without difficulty, overhydration in patients with impaired or marginally adequate cardiopulmonary reserve may lead to signifi- cant problems. Therefore, accounting for maintenance plus insensible losses, intraoperative fluids generally should be approximately 125 mL/hr for a 70-kg male.
F. Conclusions
Carbon dioxide pneumoperitoneum directly and indirectly reduces renal function during surgery and for several hours after the procedure. The main effects are decreased renal blood flow, glomerular filtration rate, and urine output. The most important causes of these effects are renal parenchymal com- pression, decreased cardiac output, and central venous compression. Elevated blood levels of antidiuretic hormone, epinephrine, endothelin, and renin con- tribute to these transient dysfunctions. In patients with normal renal function
before surgery, full recovery of renal function to baseline levels after surgery is almost always the rule. Those with significant preexisting renal dysfunction are the subgroup most likely to develop more serious renal problems during and after laparoscopic surgery. To minimize the negative impact of CO2 pneu- moperitoneum, it is important that preoperative fluid deficits be corrected.
During the operation, however, for most patients conservative intraoperative fluid administration is advised because insensible losses are usually minimal. As always, each patient must be individually assessed and scrutinized to formulate a plan that takes into account their particular situation (preoperative renal func- tion, fluid status, and anticipated operative insensible and blood losses).
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