Anesthetic Concerns in Resection of Liver: Case Series

Abstract

Liver resection is a major abdominal surgical procedure with its associated complications. A multidisciplinary team approach with appropriate preoperative planning is of utmost importance. The four cases managed successfully under general anaesthesia in a tertiary government hospital put forth a protocol based management for better outcome. The case series help to find out the perioperative anaesthetic challenges in management of liver resection. A 27-years old female and 40-years old male patients were admitted to a tertiary government hospital with diagnosis of hepatocellular malignancy and a 56-years old male and 52-years old female patients with gall bladder malignancy with liver metastases were admitted in the hospital for definitive cure. All patients were posted for tumour resection under general anaesthesia. This case series highlights the optimum preoperative preparation, optimization and discussion of perioperative concerns and anaesthesia management and importance of total intravenous anaesthesia. Role of protocol-based anaesthetic management and knowledge about surgical techniques for minimization of blood loss may decrease morbidity and mortality in liver resection surgery.

INTRODUCTION

Liver resection is a major abdominal surgical procedure with its associated perioperative complications. During the 1970s, perioperative mortality for liver resection was quoted around 20% due to uncontrollable bleeding and postoperative liver failure. A multidisciplinary team approach with appropriate preoperative planning is of utmost importance. Due to advancements in surgical technique, mortality is decreased up to 3%.[1] The balance between adequate resuscitation to ensure proper end-organ perfusion while maintaining low central venous pressure (CVP) during the parenchymal transection phase to minimize hepatic venous back bleeding is unique to liver surgery. This is a case series of four cases managed successfully under general anesthesia in a tertiary government hospital in Western India.

CASES DESCRIPTION

A 27-year-old female patient with hepatocellular carcinoma of the right side of the liver was admitted to the tertiary care hospital with complaints of pain in the right side of the abdomen for 30 days. Ultrasonography (USG) evaluation of the abdomen revealed 4 cm × 4 cm × 5 cm hepatoma of the right side of the liver.

Another 40-year-old male patient with hepatocellular carcinoma of the right side was admitted with similar complaints of pain in the right side of the abdomen for 2 months. His USG of the abdomen also revealed 5 cm × 7 cm × 7 cm hepatoma.

Computerized tomography of the abdomen of both patients confirmed the mass in the right side of the liver. Her hemogram, complete blood count, coagulation profile, liver function, and renal function tests were within normal limits. The laboratory parameters of the male patient were within normal limits.

Both patients were posted for tumor excision under general anesthesia. Patients were kept nil by mouth. After proper consent, a presurgical checklist for anesthesia and operation theater was completed; a central and arterial line were secured. Noninvasive blood pressure, electrocardiogram (ECG), pulse oximeter, and bispectral index monitor were attached. The rapid infusion system was kept ready. Baseline arterial blood gases (ABGs) were obtained. Both patients were premedicated with injection glycopyrrolate 6 μg.kg⁻¹ and injection fentanyl 1 μg.kg⁻¹. Induction of general anesthesia was done with injection propofol 2 mg.kg⁻¹ and injection succinylcholine 2 mg.kg⁻¹. Endotracheal intubation was performed with 7.5 number cuffed Portex endotracheal tube under direct laryngoscopy for female and 8.5 number for male patient. The endotracheal tube was fixed after checking of air entry bilaterally and found it equal on both sides. Maintenance of anesthesia was done with oxygen 50% with isoflurane titrated as 0.2%–0.6% to maintain a minimum alveolar concentration of 1. Nitrous oxide was avoided. Prophylactic tranexamic acid was given as an intravenous bolus of 1 g, followed by 500 mg as an infusion. Intravenous fluids were given as 20 mL.kg⁻¹ crystalloids and 500 mL of colloid as pentastarch. Vital parameters were monitored along with the bispectral index during the procedure. Glyceryl trinitrate was given during the dissection phase to keep systolic blood pressure (SBP) below 90–100 mmHg. CVP was kept up to 5–6 cm of water. During the resection phase, 400 mL blood loss occurred in the first patient and 1 L blood loss occurred in the second patient. Inotropic support was initiated with injection noradrenaline with dial a flow of 50 mL.h⁻¹. Maintenance of anesthesia was done with atracurium as muscle relaxant 0.5 mg.kg⁻¹. Hypothermia was avoided with the use of a warming system. Neuromuscular junction was reversed with injection neostigmine 0.04 mg.kg⁻¹ and injection glycopyrrolate 10 μg.kg⁻¹ and the trachea was extubated in deep inspiration after suctioning. The patients were given intravenous opioid analgesia with injection tramadol 1 mg.kg⁻¹ during the postoperative period. The patients were kept in a high-dependency unit for 48 h postoperatively and then were shifted to the ward. The rest of the postoperative course was uneventful.

The two other patients were 56- and 52-year-old male patients with gallbladder malignancy who had a history of pain in the abdomen for 5 and 8 months, respectively, with associated nausea and loss of appetite in the recent weeks. The intensity of symptoms had increased over the past 8–10 days. Vitals of both patients were normal. Airway examination was within normal limits. The laboratory parameters of both patients were normal. Echocardiography revealed an ejection fraction of 60% and 50%, respectively. USG abdomen showed a 2.8 cm × 2.4 cm hypoechoic lesion in the neck of the gallbladder suspected neoplasm in the first patient and a 3 cm × 3.2 cm mass lesion in the second patient.

The operation theater and patient preparation were similar in all four patients. The patients received general anesthesia similar to earlier described cases. The blood loss was 300 mL in the third patient and 600 mL in the fourth patient. No blood transfusion was required in the third patient. These patients received intravenous tramadol analgesia postoperatively.

DISCUSSION

Liver resection is a major abdominal surgical procedure with its associated complications. A multidisciplinary team approach with appropriate preoperative planning is of utmost importance. Advancements in anesthetic and surgical new technologies and deep knowledge of pathophysiology have allowed this surgery to become safe with low morbidity and mortality.[1] The reduction in intraoperative bleeding allowed a high survival rate.[1]

Bleeding is the most common and feared complication in liver resections.[1] Blood loss in liver surgery can occur by different factors. It is the largest internal organ with large blood volume and is crossed by large vessels.[1] In 2000, a meeting of experts with the aim of creating a definitive nomenclature describing the different interventions of the liver was performed which is the most widely accepted to date.[2] The surgery of the liver can be performed according to the lobar and segmental distribution or without respecting this division. The resection of a lobe of the liver which is hepatectomy is called right or left as per the lobe removed. It is called segmentectomy when a single segment is removed. When two segments are removed it is called bisegmentectomy. Hepatic trisegmentectomy involves removal of the right or left hepatic lobe resection plus contralateral one or two segments. Atypical liver resection involves no segmental distribution.

The most common cause of liver metastasis is colorectal cancer. Indications of hepatic resection are malignant and benign hepatobiliary tumors, living donor hepatic transplantation, and trauma.[1,2] Potential risks of surgery are intraoperative hemorrhage, hypotension, coagulopathy, renal failure, and cardiac and pulmonary complications. The liver has a dual blood supply. When the portal flow decreases, it complements the hepatic artery increasing its volume. The hepatic artery maintains a self-regulating system, which maintains its constant infusion irrespective of variations in systemic pressure. Hence, the liver can function even under adverse circumstances and can sustain hypotension. Hepatic resection implies the risk of significant bleeding within minutes of the start of surgery. Hence, it is recommended to keep CVP low during preresection phase with nitroglycerine.[3] In all four cases, the CVP was kept around 0–5 cm of water. Low CVP helps to decrease blood loss and the size of the inferior vena cava (IVC). In our cases, clamping of IVC did not result in hypotensive episodes as CVP was kept low. Communication with surgeon helped for judging the timing of IVC clamping as well as judicious fluid management during this crucial step.

The Pringle maneuver described by Pringle in 1908 limits the flow of blood into the liver.[3] It involves portal triad clamping during the resection phase. This maneuver decreases blood loss but renders the liver susceptible to warm ischemia and reperfusion injury which may lead to severe liver dysfunction and liver failure in the postoperative period. This technique can be performed intermittently in cases of hepatic fibrosis and steatosis. However, this maneuver is tolerated poorly by the liver.

Hepatic vascular control methods can be inflow or outflow vascular occlusion.[1] Another technique is total vascular exclusion which is useful in the resection of tumors adjacent to large vessels[4] which can also be done intermittently. This technique leads to a compensatory increase in systemic vascular resistance. Intermittent clamping (IC) is done with intermittent short periods of reperfusion; initially, the duration of ischemia inflicted of 15 min, followed by reperfusion for 5 min is done. Safe upper limit of IC was considered to be 120 min. Preconditioning is a phenomenon in which tissues are rendered resistant to the deleterious effects of ischemia-reperfusion either by previous exposure to brief periods of vascular occlusion or by the administration of certain chemical agents. The protocol for ischemic preconditioning (IP) is to inflict 10 min of ischemia, followed by 10 min of reperfusion before more prolonged ischemia. IP results in better cardiovascular. Decrease the blood loss but do not prevent backflow bleeding from hepatic veins.[1]

Patients who received neoadjuvant chemotherapy need special mentioning as their cardiovascular reserve may be reduced. The review of the literature suggests four basic principles to be followed while managing these patients. (1) Use of anesthetic drugs that do not alter the hepatic blood flow. (2) Maintenance of CVP between 0 cm and 5 cm of water. (3) Use of vasoactive drugs whenever needed to avoid sustained hypotension. (4) No epidural analgesia in view of the risk of coagulopathy.

Cochrane analysis[5] did not find any statistically significant difference in mortality, liver failure, intraoperative blood loss, or hemodynamic changes by IP.[6] Both the techniques of IP and IC were compared in the literature. IP is proven to be a superior technique in terms of prevention of intraoperative blood loss and the number of transfusions required and hence less intensive care unit and hospital stay. Only difference found is that IC provides protection to patients beyond the age of 65 years which IP cannot provide and also can be used in patients with steatosis. The current guidelines in literature[6] recommend IC in complex liver resection cases while IP done before continuous portal triad clamping can reduce reperfusion injury after warm ischemia. Remote ischemia preconditioning is another technique which needs further clinical trials to be included as recommended technique.

As the Pringle maneuver has its own disadvantages, hepatic blood inflow occlusion without hemihepatic artery control is a safe, convenient, and feasible method for hepatic resection in patients with cirrhosis and hepatitis.[5] Pharmacological preconditioning refers to the use of pharmacological agents before the ischemic insult to the liver during hepatic surgeries, to attenuate the effects of liver injury. Isoflurane and sevoflurane pretreatment protect from ischemia-reperfusion injury in animal models.[7] Propofol inhibits lipid peroxidation in an animal model of gut ischemia-reperfusion-induced liver injury.[8] Volatile anesthetic agents and opioids have the potential of liver protection by increasing the expression of inducible nitric oxide. Other drugs which are proven to be beneficial are verapamil and lignocaine.[9,10] Ozone therapy, adenosine, methylprednisolone, glucose, and antioxidants such as Vitamin C and E are useful but not used routinely.[11] Any anesthesia drug either given by intravenous or inhalational route that does not decrease the hepatic blood flow can be an excellent alternative instead of total vascular occlusion.

General anesthesia with controlled ventilation is the commonly employed technique.[1,12] In all these patients, premedications used were injection glycopyrrolate 5 μg.kg⁻¹, injection ondensetron 4 mg, and injection midazolam 0.5–1 mg by intravenous route. Intravenous induction was done with injection propofol 2 mg.kg⁻¹ and injection atracurium 0.05 mg.kg⁻¹. Intubation was done under vision with an appropriate-sized Portex endotracheal tube 7.5 number in female and 8.5 number in male patients. Maintenance of anesthesia was done with total intravenous anesthesia (TIVA) with atracurium as a muscle relaxant. The CVP was kept between 0 cm and 5 cm of water. Anesthetic agents with minimal impact on liver blood flow should be used but no optimal agent has been identified.[1,12] Isoflurane, sevoflurane, desflurane with atracurium, and cisatracurium are other agents that can be used.[12] All patients were given TIVA with propofol.

Monitoring should be in line with the ASA practice guidelines. Minimum monitoring standards as per the ASA guidelines were followed in all four cases. Apart from routine hemodynamic monitoring, special monitoring includes invasive arterial and CVP as well as cardiac output monitoring and if available, transesophageal echocardiography may be used. As rapid blood loss remains a possibility, care was taken to prepare for this through large bore intravenous access and the availability of a rapid infuser. During the resection phase, blood pressure was kept below 100 mmHg systolic with the use of NTG and CVP below 5 cm of water and there was maximum blood loss up to 1000 mL in the second patient which was replaced effectively. Blood transfusion was not required in the third patient. Analgesia was provided with injection fentanyl 1 μg.kg⁻¹. To reduce CVP, restricted crystalloid solutions were given. When a drop of effective blood volume occurs, the body responds with compensatory mechanisms to maintain blood pressure constant. In the first phase, neurohormonal activation flow elements derived from muscle, skin, and splanchnic circulation to vital organs begin. The vasoconstrictor effect promotes blood flow to the brain, heart, and kidney. The basic monitoring included ECG, noninvasive blood pressure, capnography, oximetry, BIS, blood sugar, ABG, and coagulation.[12] Vasoactive agents may be needed together with volume loading before clamping.[12] Low CVP avoids backflow bleeding. If fluid restriction is ineffective, nitroglycerine, diuretics, inhalational agents, or TIVA can be used.[12] However, complications of low CVP such as poor organ perfusion and venous air embolism should be avoided. If low CVP cannot be used due to comorbid condition, then selective hepatic vascular exclusion should be used as a technique of choice in communication with the surgeon. During the resection phase, stroke volume variation (SVV) of 20% while maintaining SBP and cardiac index is suggested in the guidelines.

The guidelines recommend avoidance of the use of epidural catheters due to the possibility of liver failure and clotting disorders immediately after surgery and may persist for a prolonged period.[1] Hence, epidural catheters were avoided in all these cases. Postresection, fluids should be given in a goal-directed manner. The optimal choice of fluid is not recommended in the literature, but acetate buffered solutions are preferred.[12]

Recent literature has shown the usefulness of SVV and change in systolic pressure which can be used in place of CVP intraoperatively.[13,14] These two parameters help to avoid fluctuations in hemodynamic status. Fluid overload generates pressure on the endothelial surface to damage the liver and also impairs the passage of liquids and neutrophils from one side to another. Another measure used is avoidance of PEEP. As per any major surgery, measures should be taken to avoid hypothermia.[12]

Some advanced technologies used worldwide to allow bloodless hepatectomy are ultrasonic scalpel, electrocautery, and argon hemostatic fibrin material that can be placed on the surface of the liver to promote clotting. The other practical points which should be followed during liver resection surgery are avoidance of heparin and supplementation of FFP and Vitamin K in preoperative evaluation.[1] In the Western world, the surgical technique has evolved up to the use of radiofrequency method in which special needle designs are used in the metastases which destroy the malignant lesion by emitting intense heat.[15] Laparoscopic and robotic techniques have also been used to avoid larger incisions and bleeding hence less postoperative pain.

For the provision of postoperative analgesia, thoracic epidural analgesia with catheter infusion of local anesthetics is the technique of choice in abdominal and thoracic surgeries,[12] but it cannot be considered in liver resection surgery for the following reasons. (1) In precirrhotic stage epidural catheter can cause bruising and severe neurological injury postoperatively. (2) The causes of altered coagulation profile in a patient with liver malignancy in the postoperative period include intraoperative hemodilution and prolonged residual liver parenchyma ischemia. (3) In large liver resections, altered lignocaine metabolism leads to increase in its blood concentration with the possibility of reaching toxic levels.

The other analgesic techniques which can be used are intrathecal or intravenous morphine or fentanyl. Local anesthesia whenever admitted is given in low doses of 0.15%–0.2% ropivacaine or 0.125%–0.15% bupivacaine along with epidural opioids whenever epidural analgesia is used for perioperative analgesia in liver resections. Placement of an epidural catheter before surgery and administration of local anesthetics can help to reduce CVP during resection. The technique of epidural analgesia with general anesthesia has a low rate of complications and better outcomes in clinical settings.[16,17,18] Spinal analgesia with intrathecal opioids is another technique used in clinical settings which has its advantages and disadvantages.[19] The average life of action of intrathecal morphine is 18–24 h and the onset of action is between 45 min and 75 min. The spinal dose ranges from 100 μg to 500 μg.[20] When an epidural or intrathecal technique is not possible, analgesia depends on the administration of intravenous morphine or fentanyl. Even transabdominal plane and rectus sheath block have been recommended as alternative techniques.[12] Analgesia following liver surgery remains a very controversial topic and each case should be individualized based on the liver pathology and patient profile. We preferred perioperative opioid analgesia and avoided neuraxial blockade. The condition of the liver in all four patients was not that bad.

All the perioperative techniques in liver surgery also point toward enhanced recovery after surgery (ERAS).[21] Optimizing pain management to facilitate ERAS should be the goal. A recent liver resection technique practiced in clinical settings is ex vivo liver resection. From anesthesia point of view, whenever this technique is used, CVP should not be lowered as it is difficult to maintain hemodynamic stability during this technique. Postoperative kidney failure is one of the complications of this technique.[22] Another surgical technique of which an anesthesiologist should be aware is associated liver partition and portal vein ligation for staged hepatectomy which is a recently introduced surgical technique[23] which avoids liver failure. Estimated blood loss and the number of hepatic segments resected are independent predictors of both morbidity and mortality.[5]

Postoperative morbidity up to 25% and mortality up to 5% persists irrespective of advanced technology.[12] Hence, updated knowledge of surgical techniques and protocol-based anesthesia management should be followed in liver resection surgeries to decrease morbidity and mortality.

CONCLUSION

The present case series highlights the optimum preoperative preparation, optimization, and discussion of perioperative concerns and anesthesia management. We suggest:

1. Preoperative ABG, PFT, and 2D echo are must in every patient

2. Preoperative injection ethamsylate, Vitamin K, tranexamic acid, and FFP in case of coagulopathy

3. To screen patients who are at high risk of intraoperative bleeding and postoperative liver failure

4. CVP should be maintained between 0 cm and 5 cm of water. As patients are admitted keep a track of their fluid status and they should not be overhydrated

5. TIVA is the preferred technique

6. Minimum fluids to be given intraoperatively to decrease bleeding

7. A close communication with operating surgeon for the surgical step and anticipated complications plays a key role

8. Cardiac output monitoring should be done in patients with cardiac diseases

9. Blood sugar monitoring is important

10. Coagulation profile monitoring should be done in all patients

11. Avoidance of PEEP during resection phase

12. Try to extubate the patient in the operation theater

13. No epidural analgesia in view of the risk of coagulopathy

To summarize, the risk factors for complications are ASA grading, age, extent of liver resection, need for blood transfusion, and preexisting cirrhosis.

Clinical significance

The role of protocol-based anesthetic management decreases morbidity and mortality in liver resection surgery.

Declaration of patient consent

The authors declare that they have obtained consent from patients. Patients have given their consent for their images and other clinical information to be reported in the journal. Patients understand that their names will not be published and due efforts will be made to conceal their identity but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.