Anaesthesia and the perioperative management of hepatic resection
DR. ANUPRIYA GARGUNDERGUIDANCE OF DR. AKANKSHA DUTT
IntroductionThe liver is most unusual in that it can regenerate functionallyactive tissue. Therefore, much of the liver can be removed, followedby regeneration.The liver consists largely of hepatocytes, which areunipotent cells, in that they have the capacity to develop ordifferentiate into only one type of cell. Although there is a return to the original liver mass, theshape of the regenerated liver is not fully restored. Non-parenchymal cells such as bile duct, endothelial and Kupffercells replicate more slowly.The liver regenerates rapidly over about 1 month,but functional capacity is slower to return in the larger resections.Diabetes and cirrhosis will slow this process considerably, as willsepsis or any other major perioperative complication.
This ability of the liver led to early attempts at hepaticresection.However, initially this was fraught with difficulty. In particularhaemorrhage was a major problem, because of the difficulty insuturing or sealing hepatic tissues.However, improvements in surgical and anaesthetic techniquesgradually reduced this problem.Now perioperative mortality has fallen from 20%, forty yearsago, to around 3%.
INDICATIONSThe most common indication in the UK is the removal ofhepatic metastases from colorectal carcinoma. Overall five yearsurvival is 40%, compared to close to zero without hepatic resection.Liver resection is also important for the removal of primaryhepatictumours such as hepatocellular carcinomas or biliary tumours suchas cholangiocarcinomas and occasionally following trauma to theliver.It may also be used for removal of benign liver tumours, livercysts, although deroofing and drainage may be more appropriateand for live donor liver transplantation.Segmental resections may be required as part ofhepaticojejunostomy procedures for high bile duct injuries.
Liver anatomyThe liver is highly vascular, receiving a total blood flow of 1.5 litre min,of which 80% is supplied by the portal vein and 20% from thehepatic artery.The liver can be divided into five sectors and further sub-divided intoeight functional segments ,described by their blood supply and biliarydrainage.The portal vein divides successively to supply each liver segment,reflecting similar divisions of the hepatic artery and bile duct.Segmental portal and hepatic arterial blood supply and biliary drainageare unique, so contiguous segments can be resected without disruptingthe vascular supply to neighbouring tissue.There are few bloodless planes of dissection, and functionaldivisions are invisible on the surface of the liver
Preoperative assessmentThis combines the impact of a large upperabdominal wound with surgery to the liver. The larger the liverresection more traumatic the surgerya greater potential for blood loss, lengthy clamp times and morechances of liver failure.This can be further complicated if the tumour lies close tolarge vessels, resulting in potentially greater loss of vascular supplyto liver tissue. Therefore the nature of the surgery itself is important.Laparoscopic techniques are improving,but in general are onlysuitable for relatively accessible or small lesions or liver cysts.However, anaesthetists need to be prepared for sudden conversionto an open technique.
Little data exists on precise exercise tolerance for open hepaticresection, but less than 1 flight of stairs exercise tolerance due tobreathlessness or angina, especially if combined with arrhythmiassuch as atrial fibrillation, will produce a high risk of perioperativemortality or morbidity. Low CVP levels are needed to help reduce blood loss. Therefore,diseases that increase right sided pressures in the heart may well leadto increased inferior vena caval pressures and so will increase bloodloss. Therefore, valvular lesions, such as pulmonary stenosis mayhave so severe an impact on pressure that valve replacement isrequired prior to liver surgery.
The large abdominal incision increases the risk of postoperativelung atelectasis, therefore severe chest diseases will have majorimpact on outcome.The presence of other diseases of the liver will also increase risks.Patients with Child-Pugh scores of B or C should not receive liver resection surgery because the risk of postoperativeliver failure is very high. Clotting should be normal or very close to normal if liver resection isnot going to produce severe deteriorations in prothrombin time.Platelets may be relatively low due to hypersplenism in patients withcirrhosis and a cirrhotic liver may be more prone to bleeding becauseof the texture of the liver itself and abnormal surrounding vasculature. Patients with a severely fatty liver as for example seen in extremeobesity will also be at greater risk of liver failure.
Liver function tests needs to be checked preoperatively.A low albumin may suggest early liver impairment, thereforeconsideration needs to be given to the cause of any abnormality.Is there a degree of obstruction that can be relieved at the time of theoperation or by stenting or percutaneous radiological techniques oris their insufficient functioning liver to allow for a safe resection?
Risk stratification can be improved by using indocyanine green(ICG) retention. ICG is rapidly extracted by the liver and is excretedin the bile unchanged by a first order kinetic process and has beenused to assess graft function in liver transplantation. An indocyaninegreen retention rate of 14% or below at 15 min is consideredthe safety limit for major hepatectomy for cirrhotic patients, witha maximum of 60% of non-tumorous tissue being resected. ASA grading, age, size of resection, preoperative cholangitis, elevatedcreatinine, bilirubin (and pre-existing cirrhosis), especially if followed byhigh operative blood loss have been shown to risk factors.
Surgical considerations at preoperative assessment will firstestablish whether there is disease spread beyond the liver. Singleisolated metastases beyond the liver may be amenable to palliativesurgery, but the overall outcome will be severely downgraded andso the logic of taking preoperative risks will be reduced.Surgical assessment will also consider the involvement of major bloodlevels in the metastases and whether surgery is feasible withoutSacrificing too much of the liver blood supply, hence increasing thepercentage of liver that needs to be removed.At most, 80% of the liver can be removed, but the risks of liver failureand other complications are high.If there is doubt a laparoscopic examination can beperformed before more extensive surgery is commenced.
Patients may come to theatre following chemotherapy to shrinkmetastases, especially if they are close to important vessels. Therehave been concerns that chemotherapy might impair regeneration,especially when the liver has experienced periods of ischaemia.However, although regeneration may be delayed chemotherapydoes not prevent the use of clamping of the blood supply to theliver.Commonly patients will be seen with peripheral neuropathiesafter oxaliplatin based chemotherapy. This should be documentedto avoid later confusion with potential adverse effects ofepidural blockade.
Clinical & Biochemical POINTS SCOREDvariables 1 2 3Serum albumin (g/L) >35 28-35 <28Serum bilirubin (µmol/L) <35 35-60 >60 [Mg /dl] < 2 2 -3 >3PT (seconds) prolonged 1-4 4-10 10from control INR [ < 1 .7] INR [1.7 - INR >2.3 2.3]Ascites None Mild ModerateEncephalopathy Absent Grade I – Grade III – IV II POINTS : 5- 6 – class A [5% Mortality] , 7 -9 –Class B [10% mortality], 10 -15 –Class C [50% mortality]
Polycystic disease of the liver and kidneysOccasionally, huge numbers of liver cysts may form, sometimesin association with renal polycystic disease.As well as the risk of renal impairment, the hepatic cysts mayforce the diaphragm upwards due to positional effects andincreased intra abdominal pressure, so gradually impairingrespiration .Following surgery, the diaphragm may still be overstretched andno longer be able to use the abnormal liver as a fulcrum leading toincreased inefficiency until it is able to remodel itself. Non-invasiveventilation or even respiratory support via a temporarytracheostomy may be required until remodelling occurs.
Anaesthetic techniqueProbably the most common technique is intravenous inductionwith propofol, accompanied by a remifentanil infusion, initialparalysis for intubation with atracurium and maintenance witha volatile agent such as isoflurane or sevoflurane, which has a lowchance of producing an increase in liver enzymes, whilst adding toperipheral vasodilatation, which is helpful in attaining a low CVP.Known hepatotoxins such as halothane should be avoided.Nitrous oxide should be avoided as it causes gut distension.During resection PEEP may be reduced to zero to reduce theintrathoracic pressure, so assisting venous return and lack of backpressure on the hepatic veins.
Usually, a thoracic epidural is inserted at around T8/9 or T9/10while the patient is awake. A mixture of local anaesthetic such asbupivacaine and fentanyl is usually used (depending on the centre).An epidural infusion is then maintained for the next four to fivedays. In the postoperative period after large liver resections plainbupivacaine without fentanyl may become necessary. Someauthorities argue that the risk from epidural analgesia is too greatbecause of the risk of abnormal coagulation.However, theevidence for a high rate of complications is lacking. Transfusion of fresh frozen plasma may be necessary to cover epiduralremoval in the postoperative period.
CVP and arterial lines are sited in the anaesthetic room, togetherwith a urinary catheter with temperature probe attachment. In addition to warmed fluids, two air blanket warmers are used tohelp maintain normal body temperature in the face of a largeabdominal incision and occasionally large volumes of administrationof intravenous fluids.Liver resections have been undertaken without utilising epiduralanalgesia, by using other regional techniques such as paravertebralor transversus abdominis plane (TAP) block and by using morphinebased analgesia via PCA. This removes the potential hazard of anepidural haematoma occurring if clotting problems become excessive.
However, analgesia is rarely as effective and is less reliablyprolonged and so the potential for increased incidence of respiratoryfailure is present.In large resections where liver function is reduced, intravenousanalgesia may lead to increased drowsiness, hallucinations,respiratory depression and failure to cough.Local anaesthetic toxicity can occur, but is relatively rare.Antibiotic prophylaxis of cefuroxime or augmentin andmetronidazole is given. Local policies may vary.In large resections the disruption to Kupffer cells may add to theimportance of prophylaxis.
Intraoperative managementIn addition to standard monitoring, large bore venous accessshould be established, together with central venous pressure (CVP)and invasive arterial monitoring.Monitoring cardiac output (and stroke volume variation duringmechanical ventilation) may be helpful. The use of transoesophagealechocardiography or pulmonary artery flotation catheter has also beendescribed.The key is to understand how hypovolaemia is affecting cardiacoutput and to anticipate when filling is becoming too low or converselytoo generous. This is because a low CVP will be needed to reducebleeding during the resection. Commonly, the surgeon will clamp the hepatic artery andportal veins. The route for blood loss will then be backflow throughthe hepatic veins. Therefore, it is important to maintain a low CVP,ideally not more than 5 cm H2O.
The surgeons will resect the liver using a CUSA or ultrasonicaspirator having first removed the gallbladder and mobilised theliver. This dislodges hepatic cells leaving vessels intact, so allowingthem to be clipped.Other alternatives are the clamp crushing technique or thehydrojet.Radiofrequency heated devices to reduce blood loss are also underdevelopment.Electrical cautery with bipolar forceps is also often used. The cutsurface of the liver is often cauterised with argon beam coagulation,then sealed with fibrin glue and haemostatic pads towards the end ofthe procedure.Towards the end of the procedure it is important to adequatelyrefill the circulation to enable the detection of bleeding points..
Prior to closure it is helpful for the surgeon to guide a nasojejunal feeding tube through the pylorus and beyond, as the anaesthetist advances the tube.Once in position the surgeon can maintain the position ofthe tube as any slack or kinks are removed by the anaesthetistpulling back on the tube and then after flushing with saline,removing the central stiffening wire.The tube should then be flushed again to reduce the chance ofblockage.It is common to start low dose feeding at 10 ml/h once the patient isfully awake, later on the day of surgery. This can then be increased astolerated.A nasogastric tube is also usually positioned soon after inductiontogether with the preliminary placement of the nasojejunal tube.
In radiofrequency ablation a thin needle is inserted into themetastasis within the liver. The tip is heated to 80-100 C, resultingin destruction of tumour tissue.This can be used to control some metastases percutaneously or asan addition to surgery in difficult to access areas of the liver. This hasthe potential to cause a high degree of tissue destruction and needscareful control. It may cause a SIRS response.Patients with more than two nodules of hepatocellular carcinomaand hepatitis c have a high rate of recurrence.
Problems of a low CVPPerfusion may be compromised, especially in patients with poorleft or right ventricular function. In an effort to maintain perfusionin a reduced CVP situation, many anaesthetists use an inotrope orvasoconstrictor such as a low dose of dobutamine (2-5 ug/kg/min)or noradrenaline (0.05 ug/kg/min).In the case of dobutamine it is important to ensure heart rate doesnot rise too high because of its muscle vasodilatory and chronotropictendencies.Glyceral trinitrate infusions or diuretics have sometimes been used tolower CVP, but generally are not necessary.
When running with a low CVP, a sudden loss of blood willrapidly produce severe hypovolaemia. This is why it is vital to havethe ability to rapidly infuse warmed fluids or transfuse blood, usinga rapid infusor designed for the purpose that can protect againstinadvertent air infusion. Again it is important not to excessively compensate for fluid lossand produce a high CVP that further compromises the surgeon’sability to regain control.
Watching the cut surface of the liver from the foot end of the patientmay help with understanding how the surgeon is coping.Be aware that the surgeon or his assistant may compress the inferiorvena cava with hands, retractors or packs and seriously reduce venousreturn.Therefore it is important to watch what they are doing and avoidhaving a “blood brain barrier” that can’t be seen over.
Air embolism is a hazard of a low CVP. It is important to watch forsudden falls in cardiac output, with a fall in end-tidal CO2. If suspectedinfuse fluid rapidly, inform the surgeon, who may be able to preventfurther air entering, give 100% oxygen and aspirate from PAFC if oneis in situ.In a massive embolism it may be possible to aspirate air.Small air embolisms are seen very commonly if looked for usingtransoesophagealDoppler techniques, however major embolisms arefar less common.This is in particular a potential risk during CO2 pneumoperitoneumfor major laparoscopic liver surgery. Intrapulmonary arteriovenousshunts in cirrhosis have been described as a cause of paradoxical airembolism and in a small number of patients there may be ananatomical route from the right to left heart.
Clamping of the hepatic artery and portal veinBlood loss is reduced by hepatic arterial and portal vein occlusion.Prolonged clamping will cause warm hepatic ischaemia, with thepotential for infarction as sometimes evidenced by a sharp rise in ALTand AST seen 24 h later. Most surgeons will try to restrict clamping to15 min at a time and then will reperfuse for 5min with the hope ofallowing the liver to recover.Microcirculatory changes associated with reperfusion reduce sinusoidalblood flow and prolong hypoxic effects. Intermittent clamping up to 90min in total appears reasonably well tolerated in non-cirrhotic livers.Exactly what is happening in terms of liver reperfusion injury is unclearduring this time, but it does also allow the restoration of blood drainagefrom the gut.
During clamping and particularly after major resections regularchecking of blood sugar levels usually most conveniently fromarterial blood gases is important.It is common practice to run a background infusion of 5% glucoseduring liver resections for this reason.There is some evidence mainly from hepatic transplants that N-acetyl cysteine may reduce hepatic damage during clamping.
Postoperative care The vast majority of liver resections can be woken up fromanaesthesia and extubated at the end of surgery. Occasionalexceptions are those who have experienced heavy bleeding and arestill too cold or acidotic to awaken.Waking at the end of surgery is important to minimise additionalsedation and lung atelectasis due to prolonged ventilation.In large resections there is a risk of prolongedneuromuscular blockade, which can be reduced by usingneuromuscular blocking (NMB) drugs that are not metabolisedhepatically and by reducing the amount and frequency of use.
Reversal agents are important as is electrophysiological testingwith a nerve stimulator.It is often only necessary to use a dose to facilitate intubation andsometimes for wound closure. During the rest of surgery the effect ofthe epidural and other anaesthetic drugs is usually sufficient to relaxthe abdomen.If epidural analgesia has been employed this will cover abdominalpain, although drain sites can be problematic especially if the tissuesare too tightly stretched around the drain.Unfortunately, shoulder tip pain may occur due to referred painfrom close to the diaphragm because of the similar dermatomaldistribution. Tramadol is often used to combat this pain because ofits multimodal mechanisms of action.
Patients with 40% or smaller resections who are at low risk ofhepatic failure can be managed in a similar way to most other majorlaparotomies.Early postoperative nasojejunal feeding may help maintain gutfunction and immunocompetence.Larger hepatectomies are often cared for using protocol based care.
The possibility of hypoglycemia may necessitate a glucose infusion.Secondary hyperaldosteronism is common, which promotes retentionof sodium and water and leads to oedema. Intravascular volume expansion may be aided by salt-poor 20%albumin.Correction of electrolyte disorders is commonly needed especiallypotassium and phosphate.A proton pump inhibitor may be needed. Lactulose is normally introduced if there are any signs ofencephalopathy.
ComplicationsPostoperatively,complications are frequent. Therefore it iscommonpractice for hepatic resections to spend sometimepostoperatively ona high dependency unit.This becomes progressively more importantas the size of resection increases and the number ofcomorbiditiesrises.
Intraoperatively, the commonest complications are hypotensionand bleeding. Median blood loss for a liver resection is under 0.5 l,however, the potential for massive haemorrhage exists.This meansthat in most cases transfusion can be avoided,which has been shownto reduce the frequency of recurrence of malignancy and reduce thenumber of postoperative infections.However,if transfusion requirements are likely to exceed 4 units of blood the needfor FFP should be anticipated early to maintain clotting as close tonormal as possible, with early administration of platelets when needed.
Respiratory:Most common are-atelectasis and subsequent pneumonia. It iscommon to find basal collapse especially on the right side, whichmay be compounded by a pleural effusion, especially if there isa source of inflammation below the diaphragm. Inadequate pain relief or postoperative drowsiness secondary toanalgesic or other drug therapy will lead to failure to clear secretionsand reexpand the lungs..
Some anaesthetists will recruit the lungs at the end of surgery toreduce postoperative atelectasis. Increasing postoperative atelectasis should be treated by early CPAPand where possible the patient should sit out or even mobilise withsupport.As with all major surgery DVT formation and pulmonary embolismare possible and may necessitate use of DVT filters in the inferiorvenacava, in those already on treatment or suffering from for DVT orpulmonary embolism, because of the high risks of bleedingassociatedwith anticoagulation soon after liver surgery
Gastrointestinal: The enhanced blood supply to the regeneratinghepatic remnant is associated with increased splanchnic blood flowand cardiac output. Fifty percent of patients will develop ascitestransiently, which can add to hypovolaemia.Ileus and failure to absorb are common.If the patient can be kept stable then recovery usually occurs. Signs ofliver ischaemia as evidenced from rising liver enzymes are common inthe 24-48 h after surgery.During surgery, surgeons will normally try to remove livertissue with compromised blood supply. Sudden marked rises in liverenzymes or unexpected hypoglycemia should prompt concerns overmajor ischaemia with potential portal vein thrombosis as a diagnosis.Doppler ultrasound may clarify the situation.
Markers of liver function:As well as traditional liver functiontests such as liver enzymes or bilirubin, there are markers of liversynthetic function such as prothrombin time (extrinsic or tissuepathway of coagulation which relies on hepatic production ofclotting factors I, II, V, VII, IX, X and XI, protein C, protein S andantithrombin), albumin and urea. The urea cycle occurs in the liver where it is formed from ammonia,which itself comes from metabolism of amino acids. Unsurprisingly, ifthis five stage process does not occur it leads to accumulation ofammonia and induces hepatic encephalopathy.
A climbing lactate may indicate poorperfusion of an organ or organs in the body, but may also be a signof falling liver function.To Reduce liver damage , Reducing clamp time is an importantfactor in this.However, the administration of N acetyl cysteineappears to be beneficial even in non-paracetamol induced hepaticfailure and also acts as an antioxidant.
Renal System:Oliguria is most commonly due to hypovolaemia.Cardiovascular:either hypovolaemia or arrhythmia in thosewith pre-existing heart disease or sepsis from chest or abdomen.
CNS:Drowsiness is most commonly related to opiates or otheraccumulating drugs. However, in the face of increasing liver failure,hepatic encephalopathy is possible as is hypoglycemia. Checkingammonia and glucose levels is important.Hallucinations may be related to opiate accumulation. If opiates arebeing used these should be discontinued or removed from the epiduralmix.
In summary hepatic resection is a major operation with theadditional risk of potential hepatic failure and major bleedingand the hazards associated with a large upper abdominalincision.However, with adequate selection and adequateperioperative care, 30 day mortality can fall to around 3%.Further reductions and improvements in safety for patientswith initially reduced liver function may be possible in thefuture.