Abstract
The causes of obstructive jaundice are varied, but it is most commonly due to choledocholithiasis; benign strictures of the biliary tract; pancreaticobiliary malignancies; and metastatic disease. Surgery in patients with obstructive jaundice is generally considered to be associated with a higher incidence of complications and mortality. Therefore, it poses a considerable challenge to the anesthesiologist, surgeons, and the intensive care team. However, appropriate preoperative evaluation and optimization can greatly contribute to a favorable outcome for perioperative jaundiced patients. This article outlines the association between obstructive jaundice and perioperative management, and reviews the clinical and experimental studies that have contributed to our knowledge of the underlying pathophysiologic mechanisms. Pathophysiology caused by obstructive jaundice involving coagulopathies, infection, renal dysfunction, and other adverse events should be fully assessed and reversed preoperatively. The depressed cardiovascular effects of obstructive jaundice are worth noticing because it has complicated mechanisms and needs to be further explored. Alterations of anesthesia-related drugs induced by obstructive jaundice are varied and clinicians should be aware of the possible need for a decrease in the anesthetic dose. Recommendations concerning the perioperative management of the patients with obstructive jaundice including preoperative biliary drainage, anti-infection, nutrition support, coagulation reversal, cardiovascular evaluation, perioperative fluid therapy, and hemodynamic optimization should be taken.
Keywords
anesthesiacardiovascular systemjaundice, obstructiveperioperative care;
1. Introduction
Patency of the biliary tree and free drainage of bile into the intestine are important for normal hepatic function. Substances normally excreted into the bile will accumulate in the vascular system owing to obstruction of the biliary tree and the inability to excrete bile into the intestine. These substances, including bile salts, have systemic toxic effects.1 Patients with obstructive jaundice are inclined to develop nutritional deficits, infectious complications, acute renal failure, and impairment of cardiovascular function. Adverse events such as coagulopathy, hypovolemia, and endotoxemia can be insidious and significantly increase mortality and morbidity. Postoperative morbidity of patients with obstructive jaundice is up to about 20–30%.2 The anesthesiologist and critical care team play a crucial role in the perioperative management of such patients.
Choledocholithiasis undoubtedly is the leading cause of biliary obstruction, although malignancies such as cholangiocarcinoma, periampullary and pancreatic cancers, and benign stricture including chronic pancreatitis have become increasingly prevalent.3, 4, 5 It is not surprising that iatrogenic injury of biliary tract and cholangitis are becoming more important with the increase of invasive procedures performed on the biliary tract. In China, but much less frequently in the USA, parasites absorb nutrition by attaching themselves to the walls of the bile duct, causing bile duct obstruction and fibrosis.6, 7
2. Pathophysiology of obstructive jaundice
2.1. Changes in gastrointestinal tract
2.1.1. Malnutrition
Long-term obstruction of bile can induce pathophysiological changes involving malnutrition, acute renal failure, and infections that may be fatal. Prolonged obstruction of bile can lead to: malabsorption of fats and steatorrhea; poorly absorbed fat-soluble vitamins because of impaired enterohepatic circulation; susceptibility to night blindness because of vitamin A deficiency; vitamin D deficiency and chronic cholestasis contributing to hepaticosteopathy; and neuromuscular weakness in children attributable to vitamin E deficiency.8 Deficiency of vitamin K requires vigilance especially when invasive procedures are implemented, because vitamin K plays an important role in blood coagulation. Prolonged prothrombin time is attributed to lack of vitamin K-dependent clotting factors resulting from vitamin K deficiency. If vitamin K deficiency is not treated, patients will bleed easily, resulting in unnecessary blood loss during the perioperative period.9 Sepsis may also deteriorate disseminated intravascular coagulation. In these conditions, necessary precautions should be implemented.
The presence of liver disease or a prolonged partial thromboplastin time or active hemorrhage usually indicates a serious prognosis, but appropriate replacement therapy is indicated in this situation.10 Reversal of coagulopathy is the premise not only in case of intraoperative bleeding but also for the insertion of an epidural catheter preoperatively. Hepatocellular dysfunction results in insufficient protein synthesis, gluconeogenesis, and ketogenesis disorders. Therefore, malnutrition is stubborn to correct if obstructive jaundice is not relieved promptly.11 When coagulopathy is present, it can be corrected with intramuscular vitamin K (1–10 mg). When liver failure is present, synthetic function should be the main priority for improvement. Fresh frozen plasma should be administered intravenously in emergency situations.12 Patients with obstructive jaundice need to replenish nutrients preferably through the enteral pathway. If enteral nutrition is not allowed because of gastric dilatation, clinicians should consider a nasojejunal tube feeding. If enteral nutrition is not available and meanwhile severe malnutrition exists, defined as recent weight loss of >10–15% or actual body weight <90% of ideal body weight, parenteral nutrition can be adopted 5–7 days prior to the operation and continued after the operation.
2.1.2. Bacterial translocation
The tendency of bacteria accumulated in bile to develop into infectious complications is also an important consequence of obstructive jaundice. The sphincter of Oddi presents a barrier to retrograde bacteria of the intestine under normal physiological conditions. It is believed that bacteria routinely regress into the biliary tract from the intestine.13 However, bile salts can limit their proliferation,14 and they are efficiently eliminated from bile by the reticuloendothelial system. Furthermore, bile excretion from the bile tract into the intestine can also clear bacteria.3, 13, 14, 15, 16, 17 Flemma et al13 reported that bacteria were more easily cultured from bile of patients with partial biliary obstruction than with complete biliary obstruction. This indicates that retrograde contamination of bile may be an essential factor. Alternatively, bacteria may contaminate bile possibly through the hepatic artery, the portal venous systems, or even biliary lymphatics.14, 16 Furthermore, with the absence of biliary intervention, sepsis may occur because of a combination of gut failure with increased bacterial translocation through the portal system or significant biliary colonization.18, 19 The incidence of bacterial contamination increases in patients with sphincterotomy or cholangioenterostomy and in those treated with internal biliary drains and biliary stents. About two-thirds of patients with malignant obstructive jaundice have positive bacterial cultures of bile after initial endoscopic retrograde cholangiopancreatography. Patients with a biliary intervention have a colonized rate of almost 100%, and these infections tend to be polymicrobial. Repeated reflux of bacteria and endotoxin into the vascular system eventually leads to systemic inflammatory response syndrome and even sepsis.
Bacteria isolated from bile of patients with cholangitis mainly include Gram-negative organisms: usually Escherichia coli and Klebsiella, Proteus, Pseudomonas species; and Gram-positive organisms: mainly Streptococcus and Enterobacter species.15, 20, 21, 22, 23, 24, 25 A β-lactam inhibitor combined with aminoglycoside can be used empirically. Quinolones and carbapenams excreted into the bile are generally effective monotherapy in the treatment of cholangitis.26, 27, 28 Enterococci and anaerobes targeted antibiotics can also be used in those who have antibiotic resistance, and in those with previous biliary intervention and elderly patients.29, 30 However, antibiotics alone are unlikely to be effective until effective biliary drainage has been done.
2.2. Renal pathophysiology
Patients with obstructive jaundice are considered at a particularly high risk for acute renal failure, which may be a life-threatening complication.31, 32, 33, 34, 35, 36, 37, 38 Previous study has reported that renal failure was nonoliguric in 80% and was related to severe jaundice, Gram-negative infection (42%), hypotension (31%), hypoproteinemia (30%), hyponatremia (56%), and hypokalemia (63%).39
Mechanisms of the renal failure have not been fully clarified and need to be further explored. The possible explanations may be as follows. (1) Renal failure in the patient with jaundice is associated with the presence of enteric endotoxin in the peripheral blood, and the absence of bile lead to both increased growth of the intestinal flora and absorption of endotoxin. Furthermore, cirrhosis causes increased spillover into the systemic circulation.31, 40 Endotoxin absorbed from the intestine and entering the systemic circulation may then cause renal vasoconstriction. (2) Blood loss, shifts in fluid, especially when sepsis is present, may cause severe disturbances of body-fluid compartments, which may be the basic mechanism underlying kidney dysfunction in obstructive jaundice. The risk of renal failure is increased in obstructive jaundice patients with decreased intravascular volume, especially when they undergo various invasive procedures.41, 42 Correction of volume deficits in patients with bile duct obstruction can increase renal blood flow and urine output for the excretion of hepatic metabolites, and decrease circulating concentrations of toxic substances.43, 44, 45, 46 This indicates that renal impairment is attributed primarily to a lack of renal blood flow. The most effective precaution to reduce the risk of postoperative renal dysfunction is preoperative intravenous fluid therapy to maintain an adequate intravascular volume.47 (3) Cardiovascular function in patients with obstructive jaundice is depressed,1, 48, 49, 50, 51, 52, 53 and responsiveness to the vasoactive substances is blunted.49, 50 Data in animals have demonstrated that serum jaundice decreases the heart rate, causing an early cessation of beating,53 and is associated with blunted contractile response to vasoconstrictor drugs such as β-adrenoreceptor and angiotensin II stimulation.49, 52 Depressed Cardiovascular function can give rise to low pressure of systemic circulation, then may lead to pre-renal failure. This will be described in detail below. In brief, these factors lead to reduced blood flow and renal function damage. In addition, renal impairment is partially attributed to direct toxic effects of hepatic metabolites on the kidneys.37
2.3. Cardiovascular effects
2.3.1. Vascular hyporesponsiveness
Vasodilatory properties of jaundice have been explored by both in vivo and in vitro studies in animal experimental models and in humans. Patients with both acute and chronic biliary obstruction are at particular risk for hypotension after surgery to relieve the obstruction.12 Complications are highly morbid and contribute to the high mortality.54 Zollinger and Williams55 found that patients with obstructive jaundice undergoing biliary surgery were more liable to a hypotensive crisis after hemorrhage. The same result has been found in dogs with obstructive jaundice.56 It has also been established that dogs with chronic bile duct ligation (BDL) manifested hypotension and peripheral vascular hyporesponsiveness,48, 57 could be attributed to blunted response to vasoactive agents.49, 50, 58 Although Bomzon et al59 reported that systemic blood pressure was normal at rest, there was always hyporesponsiveness for the skeletal muscle vasculature to norepinephrine in baboons. Likewise, the contractile response of arterial strips or rings isolated from rats with obstructive jaundice is markedly blunted.60 The effects of bile acids components including taurine-conjugated ursodeoxycholic acid (UDCT), taurine-conjugated chenodeoxycholic acid (CDCT), and taurine-conjugated deoxycholic acid (DCT) on vascular responsiveness have also been evaluated.61 Lautt and Daniels62 reported that intravenously administrated taurine-conjugated bile acid induced vasodilation of mesenteric and hepatic arteries in cats. Similarly, intravenous infusion of doses of CDCT and DCT, not UDCT, correlated with the increased mesenteric arterial blood flow and reduced arterial pressure.61 Vascular blunted responsiveness in jaundiced patients and experimental animals has also been suggested.56, 63, 64
The opposite conclusion, that is BDL animal models may have normal basal systemic blood pressure, has also been reported. There may be a transient hypotension during the first 1–2 days after the BDL procedure. Blood pressure in BDL rats for periods longer than 1 week returned to normal levels.65, 66 Regardless of the basal state of systemic hemodynamics, the subtle deleterious consequences of BDL on the circulation may be masked by various experimental procedures. Thus, the preliminary conclusion is that the effects of obstructive jaundice on the peripheral vasculature are the decreased vascular resistance, perhaps without decreased blood pressure. This vascular hyporesponsiveness may in some cases be manifested as vulnerability to hypotension after hemorrhage, and a higher incidence rate of postoperative complications in patients or animals with obstructive jaundice. The mechanisms may be as follows.
2.3.1.1. Role of nitric oxide
There is evidence that nitric oxide (NO), the production of endothelium-derived L-arginine, plays a role in the diminished systemic vascular resistance in cirrhotic patients. NO synthesis has been found to mediate the vasodilation and decreased vascular responsiveness that occur in response to endotoxin or cytokines.67, 68 Deoxycholyltaurine (DCT) participates in concentration-dependent vasodilation, which could be attenuated by incubation with L-NAME, an inhibitor of endothelial NO synthase (eNOS), or endothelium denudation, in rat and mouse aorta.69 Taurolithocholate (TLC), taurocholate (TC) and taurochenodeoxycholate (TCDC) have been reported to increase eNOS mRNA expression induced by cAMP and NO production.70 Moreover, there is indirect evidence concerning the enormous contribution of bile acids in the pathogenesis of endotoxemia, and the causality between endotoxin and NO production has been studied.71, 72, 73 Peripheral vasodilation occurs after endotoxin infusion in humans74 or in patients with septic shock,75 and this phenomenon can be explained by the induction of NO synthase with the increased production of NO. Considering that obstructive jaundice is always associated with endotoxemia, it is reasonable to propose that high levels of endotoxin induce a high level expression of vascular NO synthesis, thereby leading to peripheral vasodilation.76 This calls for more studies to evaluate the role of NO in the hemodynamic disturbances associated with obstructive jaundice. Furthermore, the effects of inducible NO synthase inhibitors to systemic and renal hemodynamic indices should be also evaluated.
2.3.1.2. Role of potassium channels
Dopico et al,77 using patch-clamp techniques, found that bile acids reversibly activate BKCa channels in rabbit mesenteric artery smooth muscle cells, and that endothelium-independent vasodilation can be eliminated after administration of the BKCa channel blocker. Previous studies revealed left carotid artery (LCA)-induced vascular hyporesponsiveness are mediated by the second transmembrane domain of the BK β-1 subunit.78, 79 Furthermore, LCA-induced vasodilation of arteries disappeared in BK β-1 subunit knockout mice implicating BK β-1 played an important role in LCA-induced vascular hyporesponsiveness.80
2.3.1.3. Role of receptors
Fluorescence microscopy has been used to explore the effect of bile acids on endothelial cells.81 Khurana et al69 found that the vasodilation of mouse aortic rings mediated by DCT was abolished by M3 receptor gene ablation. Likewise, a synthetic acetylcholine, which acts as an M3 receptor antagonist, can block DCT-induced vasodilation.82 These data indicate that DCT-induced vasodilation is mediated by the M3 receptor.
Farnesoid X receptor (FXR), a nuclear receptor that can regulate bile acid synthesis, is encoded by the NR1H4 gene in humans.83 The studies about the effects of FXR on vascular function became a hot spot once the identification of its expression in the vasculature was revealed.84 Because FXR belongs to transcription factor, it is expected that FXR can regulate vascular function by regulating the expression of vasoactive factors (NO). eNOS expression was significantly increased by chenodeoxycholic acid (CDCA) and GW4064 (a chemical FXR agonist) in cultured endothelial cells,85 which indicates that NO can act as a bridge between FXR and vascular vasodilation. On the contrary, when smooth muscle cells were chronically stimulated by FXR, NO-dependent vasodilation was impaired because of blunted increase of cGMP.86 Thus, acute and chronic stimulation of FXR exhibit different effects on NO-dependent vasodilation and FXR knockout model may be needed to delineate the role of vascular FXR in BA-mediated vasodilation in vascular tone.
A functionally defective expression of α-1 adrenoreceptors was found both in vivo and in vitro in a 3-day BDL rat model,87 but the response to α-2 agonists in BDL rats was unchanged. Investigators provided a hypothesis that bile acids in conjunction with accumulated endotoxin during obstructive jaundice could lead to the modification of the vascular α-1 receptor.88, 89 However, it has not been determined whether the defect of α-1 receptor was due to decreased ligand-receptor binding or not.
2.3.1.4. Others
Evidence of neural regulation of vascular tone induced by bile acids is limited. Baroreflex sensitivity is impaired in patients with obstructive jaundice, which may contribute to their enhanced susceptibility to the well-known perioperative complications. The underlying mechanisms for such a change may be associated with an increased level of plasma atrial natriuretic peptide.90, 91 However, these results are preliminary and require further study.
2.3.2. Volume depletion
The effects of obstructive jaundice on the vascular tone also include those of an exaggerated hypotensive response to volume depletion, because investigators have found that the increased risk of cardiovascular complications can be ameliorated by volume expansion prior to surgery.92 However, studies regarding intravascular volume in patients and animals with obstructive jaundice have not reached a consensus.32, 55, 56, 66, 93, 94 The conflicting results are mainly due to variations in experimental time after the BDL procedure, which is the obvious confounding factor to extracellular fluid volume. Other factors including different fluid intake, the use of diuretics, and liver disease can also influence the extracellular fluid volume.
Topuzlu and Stahl95 reported a decrease in Na absorption of proximal tubules in dogs with infusing bile intravenously. Similarly, increased Na excretion in 6-day BDL resulted from bile acid accumulation.96 Fluid absorption in proximal tubules was reduced by about 30% after the microperfusion of sodium taurocholate, which could be explained by the inhibition of sodium reabsorption.97 Intrarenal infusion of bile was reported to be associated with an increase in Na excretion, urine flow, and K excretion in dogs.98, 99 The mechanisms have not been well clarified. The dysfunction of sodium re-absorption referring to cyclooxygenase has been suggested.100 It can also be associated with a direct membrane toxicity of bile acids. Indomethacin, a nonsteroidal anti-inflammatory drug, abolished the increased PGE2 synthesis induced by the intrarenal infusion of bile acids, thereby evanishing the natriuresis, indicating increased PGE2 is also involved in impaired renal conservation. On the contrary, the effects of chronically accumulated bile acids were described to increase Na and water absorption in BDL animals.66, 101, 102, 103 Likewise, natriuretic response to extracellular volume expansion was impaired in chronic BDL dogs.101 Electroneutral Na/H antiporter may play a fundamental role in changes of secretion and reabsorption of Na in the proximal tubule, and it can be regulated by sulfated bile acids at low concentrations (30 μM).104 Patients with obstructive jaundice were generally accompanied with elevated sulfated bile acid in the plasma and urine,105 which lends further credence to the pathophysiological mechanism. Patients with chronic obstructive jaundice manifest consistent results with the experimental studies.106 Thus, acute and chronic stimulation of bile acids exhibit different effects on electroneutral Na/H antiporter. Its overexpression and a knockout model may be needed to determine the role of electroneutral Na/H antiporter in Na excretion.
2.3.3. Cardiac depression (jaundice heart)
Bile acids have direct effects on myocytes, and can influence myocardial conduction and contraction. Actually, the effects of bile acids on the heart were reported long ago. Binah et al1 found that bile acid induces a negative inotropic effect manifested as maximum rate of tension relaxation, maximum rate of tension activation, and a reduction inactive tension. King and Steward107 indicated that an atropine sensitive bradycardia and hypotension were induced by biliverdin in dogs mediated by cholinergic mechanisms. Serum containing jaundice from common BDL rats can exert inhibition to cultured heart cells, which manifests as decreased beating rate, an early cardiac arrest, and production of higher levels of lactate in the media.53 Dose-dependent bradycardia was found in 7-day BDL rats and in the infusion of cholic acid, which can be inhibited by vagotomy and atropine.108, 109 These early studies provide initial evidence that bile acids can exert a direct effect on cardiac function. The mechanism may be as follows.
2.3.3.1. Changes of membrane current
The effects of bile acids on the contractile force and the electrophysiological properties of rat ventricular muscle have been studied extensively. Alternations of membrane currents are probably responsible for the negative inotropic effect of bile acids. Voltage clamp experiments in rat ventricular myocytes showed that sodium taurocholate decreases the slow inward current and slightly increased the outward potassium current.1 Kotake et al110 demonstrated that sodium taurocholate slows the spontaneous discharge of the sinoatrial node through decreases in both inward and outward current systems. Taurocholate can alter calcium dynamics characterized as cellular calcium overload or a biphasic change in calcium wave frequency.111, 112 Sodium taurocholate reduces the duration of the action potential due to the suppression of the slow inward current of calcium.1 From the foregoing discussion, the “pacemaker” function of cardiac myocytes was altered by bile acids.
2.3.3.2. Membrane receptors
Guanosine-binding protein coupled receptor may be a potential target of bile acids. Muscarinic receptor activation by bile acids as well as those needed for acetylcholine production may play key roles.113 Bile acid taurocholate binding to the muscarinic M2 receptor in cultured neonatal rat cardiomyocytes exerted an inhibitory effect on intracellular cAMP and negative chronotropic response.114 Likewise, taurochenodeoxycholic acid and lithocholic acid inhibited glycogen synthase kinase-3β, and led to multiple adaptations including metabolism, electrophysiology, and cardiac hypertrophy in the mouse heart.115 The relationship between TGR5 (a novel G-protein-coupled receptor mediating several nongenomic functional responses induced by binding of bile acids) and modulation of cardiac function has not yet been established, and calls for more definitive experiments. In summary, considering the interactions of bile acids with multiple receptors, receptor-specific effects of bile acids on cardiac function can be elucidated by the availability of knock-out mice.
2.3.3.3. Vagal stimulation
The negative effects of bile acids on cardiac function are induced by vagal stimulation and can be eliminated by atropine.108, 109, 116 Bradycardia caused by vagal stimulation can be antagonized by sodium tauroglycocholate.
2.3.3.4. Energy depletion of cardiomyocytes
Bradycardia, increase in PR and QT intervals, and arrhythmia can be attributed to a depletion of intracellular glycogen and defective energy metabolism within the cardiac myocyte.117
2.3.3.5. Bile interference
Joubert108 found that cholic acid has a dose-dependent negative chronotropic effect on isolated atria of Wistar rats, and bile acids exert a negative chronotropic effect by forming a monolayer on the surface of the cell membrane, thereby mechanically interfering with membrane function.
2.3.3.6. Others
Indirect evidence suggests that there are additional mechanisms that mediate bile acid-induced suppression in cardiac function. Serum levels of atrial natriuretic peptide can be increased by the bile constituents.118 The relationship between elevated atrial natriuretic peptide (ANP) levels and myocardial dysfunction has been established by the same group.159 Obstructive jaundice relieved by biliary drainage can both reduce ANP levels and improve cardiac function.119 It is reasonable to infer that bile acids can induce ANP release from cardiomyocytes, which may be the possible mechanism. Traditionally, this hemodynamic instability is attributed to the presence of large anatomical arteriovenous shunts. There is, however, no clear evidence that any of these agents are involved in the pathogenesis of hypotension in liver disease.120
3. Obstructive jaundice and anesthesia
Hepatic blood flow may be affected (reduced) by obstructive jaundice through various mechanisms.121, 122 Furthermore, obstructive jaundice may cause hepatic cell damage via various mechanisms.123, 124 Patients with obstructive jaundice have different levels of hepatic dysfunction, and impaired hepatic elimination (i.e., metabolism, biliary excretion, or both) of drugs in general is to be expected. Therefore, the use of anesthetics in patients with obstructive jaundice poses a considerable challenge to the anesthesiologist and the intensive care team. Interaction of unconjugated bilirubin with synaptosomal membrane vesicles leads to oxidative injury, loss of membrane asymmetry and functionality, and calcium intrusion, thus potentially contributing to the pathogenesis of encephalopathy by hyperbilirubinemia.125, 126, 127 Furthermore, acute hyperbilirubinemia induces presynaptic neurodegeneration at central glutamatergic synapses.128 Unconjugated bilirubin may also disorder the release and uptake of the neurotransmitter glutamate,129, 130 indicating possible excitotoxic damage. Therefore, the pharmacokinetics profile of anesthesia-related drugs, especially those that target the central nervous system, changes owing to the pathological mechanism described above. We have done a series of studies about alteration of anesthesia-related drugs in patients with obstructive jaundice.
The MACawake of desflurane is statistically reduced in obstructive jaundice patients compared with nonjaundice controls; moreover, the concentration of serum total bilirubin is inversely correlated with the MACawake of desflurane in jaundiced patients.131 Likewise, compared with controls, patients with obstructive jaundice have an increased sensitivity to isoflurane, and are vulnerable to hypotension and bradycardia during anesthesia induction and maintenance.132 As both isoflurane and desflurane possess relatively low blood solubility and undergo minimal metabolism in vivo, the pharmacokinetic characteristics are unlikely to be significantly different in obstructive jaundiced patients, even though liver function is impaired. As it is known that the targets of anesthetics inducing hypnosis and amnesia locate in the brain,133 alteration in the functional status of the brain secondary to obstructive jaundice seem to be a more likely reason for the increased hypnotic potency of isoflurane. Recently, it has been suggested that defective serotoninergic neurotransmission, which is considered to be sensitive to inhaled anesthetics,134, 135 and neurotoxicity of jaundice in the brain may partly contribute to the reduction of anesthetic requirement.136 Cardiovascular function should be monitored closely in these patients and clinicians should be aware of the possible need for a decrease in the anesthetic dose.
Obstructive jaundice does not affect the pharmacokinetics of propofol administered by a single intravenous bolus.137 By contrast, etomidate requirements to reach a predefined level of anesthesia were reduced in patients with obstructive jaundice.138 The difference between etomidate and propofol sensitivity in patients with obstructive jaundice can be partly attributed to the different targets of two drugs. Propofol not only inhibits the function of γ-aminobutyric acid (GABA) via GABAA receptors, but also acts at other receptors (e.g., glycine, M1 muscarinic, and nicotinic receptors).139, 140 By contrast, etomidate is a pure hypnotic GABA agonist.141, 142, 143 Also, GABA/glycinergic synaptic transmission can be enhanced by bilirubin in lateral superior olivary nucleus neurons, which theoretically could lead to increased etomidate sensitivity.144 Accordingly, extra-hepatic metabolism of propofol may be present. However, this is a very preliminary hypothesis, and it calls on more studies to determine the specific mechanisms. It is well known that propofol has the effects of cardiovascular depression, and patients with obstructive jaundice are prone to hypotension and vascular hyporesponsiveness, so it is debatable whether propofol can be used in jaundiced patients. Propofol depresses cardiac parameters at low and intermediate doses to a similar degree in BDL-treated and sham-operated rats; however, at a high dose, propofol may cause exaggerated cardiac depression in jaundiced rats.145 Interestingly, propofol itself might have eliminated the risk factors and protected the cardiovascular function.146 The possible cardiovascular protective effect of propofol under clinical conditions is not yet clear. Vascular endothelial cells play a pivotal role in maintaining cardiovascular homeostasis. Propofol can reduce H2O2-induced damage and apoptosis in endothelial cells and increase protein kinase C activity in rat ventricular myocytes.147, 148 It has been reported that administration of a large dose of propofol during cardiopulmonary bypass attenuates postoperative myocardial cellular damage as compared with small-dose propofol anesthesia.149 Therefore, propofol is a safe alternative anesthetic agent in patients with obstructive jaundice and normal cardiac function at low and intermediate doses.
Rocuronium, a quaternary aminosteroidal neuromuscular blocking agent, is eliminated unchanged, principally in bile, whereas urinary elimination is a minor pathway.150, 151 However, no significant reduction in rocuronium infusion requirements was observed during the anhepatic phase compared with the paleohepatic phase, which was documented by studies in patients with liver transplantation.152, 153 In addition, two previous studies reported that the plasma clearance of rocuronium was not significantly influenced by dysfunction of the liver or kidney.154, 155 Hence, it seems that other pathways, maybe kidney, instead of liver excretion may contribute to the continued clearance of rocuronium as concentrations continued to decrease,153, 156 and organic anion transporting polypeptides seem to take responsibility for the extra-hepatic excretion of rocuronium because of its wide expression in various organs and involvement in the absorption and elimination of rocuronium. However, obstructive jaundiced patients without renal or hepatic dysfunction had a prolonged neuromuscular effect of rocuronium caused by some other mechanisms.157, 158 The metabolism profile of rocuronium is not well understood. Further studies focusing on the hepatic function and serum jaundice respectively are needed.
4. Summary
Issues including preoperative biliary drainage, nutritional support, cardiovascular assessment, perioperative fluid therapy, and hemodynamic optimization are the main considerations for anesthesiologist and clinicians, and the corresponding treatment and monitoring concerning the perioperative management of patients with obstructive jaundice should be taken. There are still many complex pathophysiological mechanisms that require further study in obstructive jaundice. Based on current knowledge, clinicians and anesthesiologists should optimize perioperative management of the patient with obstructive jaundice.