Analgesia for Donor Hepatectomy: Recent Perspectives

Abstract

Background:

Donor hepatectomy is a complex surgical procedure associated with significant postoperative pain, which can impact both short-term recovery and long-term outcomes. Adequate pain management plays a crucial role in ensuring the well-being of the living liver donor and optimising their overall experience. This review aims to provide a comprehensive overview of current practices and emerging strategies in analgesic management for donor hepatectomy.

Methodology:

To find relevant material, searches were conducted on PubMed and Google Scholar. The evaluation took into consideration review articles, clinical trials, retrospective studies, observational studies, and case-control studies.

Results:

The conventional approach to pain control involves a multimodal strategy combining opioids, non-steroidal anti-inflammatory drugs, and regional anaesthesia techniques. However, concerns regarding opioid-related side effects and potential complications have prompted a re-evaluation of analgesic protocols. Alternative methods such as thoracic epidural analgesia, transversus abdominis plane blocks and continuous wound infusion systems have gained attention for their potential to minimise opioid requirements and enhance recovery. Recent advancements in the field of pain management, including the utilisation of enhanced recovery, after surgery protocols, personalised analgesic regimens, and novel pharmaceutical agents, are explored in this review. Additionally, the impact of psychological factors and patient-centred care on postoperative pain experiences is discussed.

Conclusion:

The review concludes by emphasising the importance of tailoring analgesic strategies to individual patient needs and characteristics. It highlights the potential benefits of incorporating innovative approaches to enhance pain control, reduce opioid consumption and ultimately improve the overall outcome and satisfaction of living liver donors undergoing hepatectomy. Future directions in research and clinical practice are also suggested to further refine and optimise analgesic management in the context of donor hepatectomy.

Introduction

Living donor liver transplantation (LDLT) has indeed been a ground-breaking advancement in liver transplantation, initially for paediatric cases^[1] and later extended to adults. Its integration alongside deceased donor liver transplantation has significantly expanded the donor pool, offering hope to patients in need of liver transplants. The altruistic nature of living donors underscores the importance of prioritising their safety and ensuring optimal analgesia during the donation process. This not only respects their selfless act but also contributes to fostering a positive environment for future donations.

Pain management after open donor hepatectomy involves addressing two major mechanisms: peripheral nociceptor stimulation (induced by subcostal incision,^[2] rib retraction, diaphragmatic irritation, etc.) and visceral origin transmitted by sympathetic nerves. Various perioperative strategies have been evaluated, including thoracic and lumbar epidural catheters, opiates via patient-controlled analgesia or continuous infusion, nerve blocks, intrathecal opiates, non-steroidal anti-inflammatory drugs and magnesium. However, there is no consensus on the best practice yet. Inadequate pain control can lead to increased morbidity, functional limitations, patient dissatisfaction, impaired quality of life, higher medical costs, longer hospital stays and potential for chronic pain and long-term opioid use. Hence, clinicians caring for this donor population must be aware of a wide range of perioperative multimodal analgesia strategies.

Traditionally, pain management for liver resection surgery relied on systemic opioids. However, these drugs are associated with risks of respiratory depression, nausea and constipation, prolonging hospital stay and hindering recovery. This review article emphasises the importance of a multimodal approach, combining various analgesic techniques to achieve optimal pain control while minimising opioid use.

Enhanced Recovery After Surgery in Donor Hepatectomy

The enhanced recovery after surgery (ERAS) approach has been developed to provide an evidence-based and multidisciplinary framework for perioperative care, including protocols specifically tailored for living donor hepatectomy.^[3,4] These protocols emphasise multimodal analgesia with opioid-sparing techniques such as intrathecal morphine, thoracic epidural analgesia (TEA), transversus abdominis plane (TAP) blocks, dexmedetomidine infusions and local injection of liposomal bupivacaine. Key principles of ERAS include preoperative counselling, preoperative nutrition, avoidance of perioperative fasting, carbohydrate loading preoperatively, standardised anaesthesia and analgesic regimens (mainly non-opioid analgesia), and early mobilisation. By minimising surgical stress and maintaining metabolic homeostasis, ERAS pathways aim to enhance postoperative recovery.

The management of postoperative pain in living liver donors is crucial, and ERAS protocols emphasise achieving adequate pain control while minimising opioid use and optimising analgesia. Traditional analgesic regimens relying mainly on opioids can lead to adverse effects, such as sedation, respiratory depression, postoperative nausea and vomiting (PONV), urinary retention and ileus, potentially delaying patient recovery. Therefore, ERAS protocols promote a multimodal analgesic approach to balance improved outcomes with potential risks, avoiding negative effects associated with excessive opioid use.

Laparoscopic Versus Open Hepatectomy

Laparoscopic techniques for graft resections, such as right hepatectomy, are increasingly being embraced due to their technological advancements and potential advantages.^[5,6] Living donors who undergo pure laparoscopic right hepatectomy have demonstrated enhanced postoperative results in comparison to open donor hepatectomies. These benefits encompass a decrease in postoperative pulmonary complications, lower opioid usage until postoperative day 7, and shorter hospital stays. Although perioperative complications like PONV and pruritus were comparable between laparoscopic and open procedures, laparoscopic donors encountered fewer overall postoperative pulmonary complications.

The benefits of laparoscopic procedures in diminishing pulmonary complications are linked to minimal direct harm to the diaphragm and respiratory muscles during the operation, along with decreased postoperative pain that aids in promoting deep breathing and active coughing during the recovery period. These elements contribute to a more seamless postoperative recovery and improved outcomes for living donors undergoing laparoscopic graft resections.

Modalities of Pain Management

TEA

TEA has long been considered the gold standard for pain relief in open donor hepatectomy.^[7] Numerous studies and trials have consistently shown that TEA is more effective than other methods in terms of providing analgesic relief for donors undergoing hepatectomy. However, there are concerns regarding its intraoperative use due to the potential development of coagulopathy after liver resection or intraoperative vascular clamping. These concerns have been further exacerbated by the emphasis on early postoperative mobilisation in ERAS protocols, which has led to a decrease in the use of TEA in recent years. Postoperatively, the majority of donors develop coagulopathy, with elevated international normalised ratio (INR) levels and decreased platelet counts, despite having normal liver function before surgery. These coagulation disorders pose a risk for epidural haematoma and subsequent neurological injuries, as well as unplanned delays in the removal of the epidural catheter due to concerns about coagulopathy.^[8] Additionally, the potential hemodynamic effects of vascular clamping and the need for early mobilisation in the context of ERAS have also contributed to the avoidance of TEA in liver resection patients. The risk of spinal haematoma after epidural analgesia remains a topic of debate, particularly in the presence of coagulation disorders following liver resection. Another drawback of TEA is the potential for delayed ambulation due to orthostatic hypotension or the use of cumbersome equipment. However, recent evidence and studies suggest that TEA can still be integrated into ERAS pathways. To achieve optimal recovery outcomes with TEA, careful consideration must be given to the level of epidural catheter insertion (mid-thoracic) and the doses of local anaesthetics used to ensure adequate pain coverage without causing motor blockade. Until the safety of epidural techniques can be definitively established in these patients, many anaesthesiologists prefer less invasive regional anaesthetic techniques.

Intravenous Patient-controlled Analgesia Opioids

Pain management strategies for individuals undergoing living liver donation have traditionally relied on high doses of opioid medications, particularly morphine, for perioperative pain relief. Opioids continue to be the primary approach for managing postoperative pain in patients who have undergone open donor hepatectomy. Along with the common side effects associated with opioids, such as sedation, nausea, itching and constipation, these medications are extensively metabolised by the liver. This can present challenges in adjusting the dosage accurately and may increase the risk of accidental overdose in patients with a small portion of their liver remaining after extensive hepatectomy, as required for living liver donation. Intravenous patient-controlled analgesia (IV-PCA) utilising opioids like morphine and fentanyl is also an effective method for managing pain after surgery.^[9] IV-PCA can facilitate early mobilisation, reduce respiratory complications, and minimise sedation, thereby enhancing patient satisfaction.^[10] Potential side effects of IV-PCA with opioids include PONV, and in cases of overdose, respiratory depression may occur. Combining droperidol or ondansetron with opioids in the PCA pump is an effective approach for managing PONV.

Dexmedetomidine

Dexmedetomidine (DEX), a highly selective alpha-2 receptor agonist, is increasingly utilised in anaesthesia due to its sedative, hypnotic, anxiolytic, sympatholytic and analgesic properties.^[11] It helps in reducing perioperative stress and inflammation, leading to improved clinical outcomes and decreased postoperative morbidity. DEX shows promise in being a part of multimodal analgesia strategies and aligning with the goals of ERAS protocols. A Cochrane review highlighted that perioperative use of DEX during abdominal surgery resulted in reduced opioid consumption within the first 24 hours postoperatively, although it did not significantly impact postoperative pain intensity compared to a placebo. Studies focussing on living donor hepatectomy have suggested that intraoperative administration of DEX could enhance postoperative analgesia and reduce opioid requirements. While DEX administration can protect patients from noxious stimuli, it may lead to adverse cardiovascular responses due to its mechanism of action. Research indicates that bolus injections or loading doses of DEX are associated with cardiovascular events and other side effects. Recent studies have demonstrated that omitting the loading dose and using only maintenance dose infusions (ranging from 0.2 to 0.7 mcg/kg/hr) can provide effective postoperative analgesia without cardiovascular risks.^[12]

Magnesium

Magnesium functions as an antagonist to the N-methyl-D-aspartate (NMDA) receptor, resulting in an analgesic effect.^[13] This property makes magnesium a potential alternative or adjunct to opioids for pain management. In the context of analgesia, magnesium sulphate has been utilised as part of a multimodal approach, as it has the potential to decrease opioid consumption within the initial 24 hours following surgery and alleviate postoperative pain. By targeting various receptors in the pain pathway, it is possible to optimise analgesia and minimise side effects. Magnesium acts as an antagonist to the NMDA receptor and inhibits calcium channels, thereby modulating pain and inflammatory responses. Administering magnesium perioperatively can be considered a strategy to reduce postoperative pain in patients undergoing donor hepatectomy,^[2] as it has demonstrated beneficial effects.

Ketamine

Ketamine acts as an NMDA receptor antagonist and enhances postoperative pain relief in cases of moderate-to-severe pain during surgical procedures. The utilisation of perioperative ketamine in managing pain for patients undergoing LDLT has been thoroughly investigated. Research has demonstrated that administering low doses of ketamine to donor hepatectomy patients perioperatively results in reduced opioid analgesic needs, lower pain scores and impacts various perioperative surgical factors, ultimately leading to enhanced recovery and decreased opioid requirements.^[14] Ketamine has been linked to the reversal of opioid tolerance without any documented interactions with other medications. Therefore, ketamine serves as a valuable supplement to opioids for effective pain management.

Gabapentin

The utilisation of oral preoperative gabapentin has been recognised as a supplementary measure to enhance pain management.^[15] At present, there exists no established protocol concerning the most effective dosage and duration of perioperative therapy, resulting in the adoption of various approaches. Following oral intake, gabapentin requires approximately 6 hours to achieve therapeutic levels in the cerebrospinal fluid. This process is linked to the reduction of central nervous system sensitisation, underscoring the significance of the timing of administration.

TAP Block

Ultrasound-guided regional anaesthesia through TAP block is a modern and safer approach that can be applied to patients undergoing donor hepatectomy.^[16] TAP block has been shown to offer effective postoperative pain relief following donor hepatectomy. It has the added benefit of reducing the need for opioids during the perioperative period, maintaining hemodynamic stability during surgery and facilitating a quicker recovery from anaesthesia. The blockade of sensory nerves is achieved within the neurofascial plane situated between the internal oblique and transversus abdominis muscles. This can be accomplished using either a landmark technique or ultrasound guidance. TAP block works by targeting the somatic aspect of pain while leaving the visceral component unaffected.^[17] Management of visceral pain can be achieved through the use of NSAIDs, paracetamol, tramadol and gabapentin, among other medications. TAP block is commonly performed in open or laparoscopic donor hepatectomies as part of a multimodal analgesic approach in various clinical settings.

Quadratus Lumborum Block

The quadratus lumborum (QL) block is a recently described fascial plane block that involves injecting local anaesthetic near the quadratus lumborum muscle to achieve anaesthesia and block the thoracolumbar nerves.^[18] This block can provide extensive sensory blockade from the T7 to L2 level. Numerous studies have demonstrated the successful use of the QL block in various surgical procedures, such as breast, abdomen, hip and lower extremity surgeries. In comparison to the TAP blockade, which only provides somatic anaesthesia of the abdominal wall and relies on the interfascial spread, the QL block may offer superior coverage, especially for the most cephalad aspect of a ‘J’ incision. Although there is a lack of direct comparison between these two techniques in hepatectomy, some studies have suggested the superiority of the QL block over TAP blocks.

Erector Spinae Plane Block

Erector spinae plane block (ESPB) is a novel technique for regional anaesthesia that has shown promising results in abdominal surgery. According to published reports, ESPB can effectively provide analgesia in the abdominal region when performed at lower thoracic levels, specifically T7-8. Initially, ESPB was described for thoracic analgesia at the T5 transverse process level.^[19] The technique targets a plane below the erector spinae muscle, which is superficial to the vertebral column and away from major neurovascular structures. In case of a haematoma at the ESPB^[20] injection/catheter site, it can be easily managed through compression without affecting the spinal cord, as it is protected by the vertebrae. When compared to neuraxial techniques like epidural catheters or paravertebral blocks, ESPB appears to have a lower risk of causing neurovascular injury, especially in cases where there is an elevated INR following haematoma formation. Studies have demonstrated that continuous erector spinae plane blockade, using ESPB, is an effective method for providing analgesia in living liver donors, leading to reduced opioid requirements during and after surgery. Patients who received ESPB required significantly lower amounts of opioids to achieve the same level of pain relief compared to those who did not receive the blocks.

Intrathecal Morphine

In comparison to neuraxial anaesthesia techniques,^[21] intrathecal morphine offers a simpler and faster alternative with a lower rate of technical failure. Limited trials have suggested that single-shot intrathecal morphine can effectively provide analgesia for open hepatectomy procedures.^[9] However, the primary concern with the use of intrathecal morphine is the increased risk of postoperative respiratory depression. Therefore, patients who receive intrathecal opioid analgesia require close monitoring in a post-anaesthetic care unit or intensive care unit after the operation, along with oxygen support. It is essential to have naloxone readily available to reverse opioid-induced respiratory depression.

Thoracic Paravertebral Block

Number of studies have suggested that right thoracic paravertebral block^[22] is a possible analgesia option for patients undergoing hepatectomy. It can be used in patients in whom epidural block is contraindicated. The risk of spinal haematoma is usually rare with the use of paravertebral block. Since a unilateral thoracic paravertebral block confers only ipsilateral pain relief with inconsistent block below T12, ‘rescue’ analgesic in form of morphine is usually required during the postoperative period. Since hepatic clearance might be reduced in patients with compromised liver function, continuing an infusion much beyond 48 hours after hepatectomy is not advisable till more data on local anaesthetic pharmacokinetics after thoracic paravertebral infusion is available.

Conclusion

A crucial aspect of living donor hepatectomy, which is the paramount importance to donor safety is effective pain management. Indeed, finding the optimal pain management regimen for open donor hepatectomy is a topic of ongoing discussion and research in the field of transplantation medicine. Blended multimodal approaches, which combine different analgesic modalities, have shown promise in providing effective pain relief with reduced side effects.

To achieve true clinical effectiveness in pain management for open donor hepatectomy, a standardised approach is needed. This approach should consider factors, such as the degree of pain experienced by individual donors, the invasiveness of analgesic interventions and the balance between efficacy and adverse effects. Continued research and collaboration among healthcare providers are essential in refining pain management strategies and improving outcomes for living liver donors.