1 Introduction

Liver transplantation (LT) since its inception has undergone a paradigm shift not only in terms of technique and perioperative patient management, but also in terms of recipient outcomes following transplant. While deceased donor liver transplantation (DDLT) is the predominant form of LT performed in the West, lack of adequate number of deceased donations, fueled the need for living donor liver transplantation (LDLT) in the East [1]. Today, Asia leads the world in terms of numbers of LDLTs, technical innovations, and success with LDLT, with some centers performing more than 200 LTs annually [2].

With the increasing feasibility and acceptable outcomes with LT in patients with end-stage liver disease (ESLD), the focus has now shifted from just “good” postoperative recovery to “rapid” recovery, and early discharge from hospital. The concept of “fast tracking” liver transplant recipients has thus emerged.

Traditionally, all liver transplant recipients have been subjected to a certain mandatory period of mechanical ventilation in ICU, with gradual weaning off. This practice of mandatory mechanical ventilation in patients after a major surgery was first challenged in cardiac anesthesia by Prakash et al. [3], and then expanded to other surgical disciplines, and major surgical procedures including LT.

The multisystem effect of ESLD, associated comorbidities typically seen in these patients like diabetes mellitus, obesity, cirrhotic cardiomyopathy, and sometimes a poor performance status makes immediate extubation difficult after LT. However, with evolution of the surgical and anesthetic practices successful early extubation and fast tracking in liver transplantation has indeed become a reality, and its implementation can be further expanded, especially in experienced and high volume centers.

2 Definition and Evolution of Fast Tracking in LT

“Fast tracking (FT)” aims at rapid progress from preoperative preparation to surgery and early discharge. There are varying definitions of FT in LT. While some authors have restricted it to on-table (in the operating room) extubation [4], others have broadened the use of the term to include tracheal extubation within 3 h of surgery [5]. Recently, complete avoidance of ICU has also been incorporated in the concept of fast tracking [6].

Prakash et al. [3] first demonstrated that early extubation either immediately or within 3 h of a major surgical procedure was possible. His team successfully extubated 123 out of 142 adult patients within 3 h of open heart surgery.

The concept of early extubation with its attendant benefits was then further extrapolated to other major surgeries including liver transplant recipients [4]. Rossaint et al. [7] reported that they were successful in extubating 5 out of 36 recipients immediately after LT, and the rest was extubated within an average of 6 h after LT. There were no pre-defined selection criteria in their study for immediate extubation. Based on their findings, they proposed that use of minimal fluids during the surgery was one of the keys to early extubation. Fluid management in their patients was based upon fall in cardiac index and ventricular filling pressures.

Mandell et al. [4] further evaluated the feasibility and cost effectiveness of fast tracking in liver transplant recipients in two institutions, University of Colorado (UC) and University of California at San Francisco (UCSF). At UC, pre- and intraoperative criteria, derived from retrospective analysis of patients who were successfully extubated within 8 h of surgery, were established. UNOS status 3/4, absence of comorbidities, age <50 years, and no hepatic encephalopathy were preoperative criteria; whereas, good donor liver function, <10 units of packed RBC transfusion during surgery, no vasoactive support at the end of surgery and alveolar-arterial oxygen gradient <150 mmHg were the intra operative criteria, which could predict planned extubation in the OR and FT. At UCSF, patients were given trial of extubation without any pre-structured criteria, based on clinical judgment of the attending anesthesiologist. Sixteen of 67 patients at UC, and 25 of 106 patients at UCSF, were immediately extubated. Retrospective comparison of the results between two universities also proved the cost effectiveness and feasibility of successful immediate extubation.

These initial studies were then followed by attempts at early extubation in other LT centers around the world. Two of the largest published series included those reported by Baincofiore et al. (211/365 recipients extubated on table) and Skurzak et al. (575/652 recipients extubated on table) [8, 9]. In their experience over 5 years, Biancofiore et al. [8] noted a progressive increase in the fraction of patients who were immediately extubated in OR as the study period progressed, and towards the end of the study period, 82.5% of recipients were extubated on table. Only 2 of the 211 immediately extubated patients needed re-intubation. Their study showed that the MELD score of 11 had the best predictive value for rapid extubation. Skurzak et al. [9] generated a prognostic score for safe operating room extubation after liver transplantation (SORELT) score (Table 37.1) based upon the data from 597/652 patients extubated on table.

Table 37.1 Proposed clinical criteria for operating room extubation after liver transplantation
Full size table

With the success of early extubation in the OR, the concept of fast tracking was given a further impetus by Mandell et al. [11] publishing their successful attempt to directly shift the extubated patients to surgical ward, thereby completely bypassing the ICU. Out of 147 patients enrolled in the study, 111 were extubated immediately post-surgery. 83 patients /111(74.7%) and 28/111 (25.3%) were successfully transferred to surgical ward and IMCU respectively, without intervening ICU care.

3 To Fast Track or Not? That’s the Question

3.1 Be Careful Before You Fast Track

Historically, LT recipients have been electively ventilated for 48 h with the rationale that positive pressure ventilation with sedation may decrease surgical stress, improve hemodynamic stability, and facilitate early recovery [14]. Although there is evidence in favor of early extubation protocols, still a section of clinicians prefer the traditional approach of a certain mandatory period of postoperative mechanical ventilation followed by gradual weaning off.

Liver transplant being a complex procedure is associated with extreme hemodynamic alterations often putting the recipients and their cardiopulmonary system under varying degrees of stress, and the practice of early extubation may not provide the required time for the patient to recuperate.

A period of mechanical ventilation and gradual weaning off allows optimization of the cardiopulmonary system and promotes recovery from the stress of surgery. The possible need for re-explorations also adds to the reluctance in early extubation.

3.2 Benefits of the Fast Track Approach

Proponents of early extubation often argue in favor of avoiding the complications associated with mechanical ventilation. Kaiser et al. [15] reported the negative impact of PEEP on liver graft hemodynamics. This was, however, challenged by Saner et al. [16] who proposed that a PEEP of up to 10 mbar did not influence hepatic arterial and venous flow. Although controversial, positive pressure ventilation can alter the liver hemodynamics adversely, thereby early extubation helps in preventing graft dysfunction from impaired hepatic hemodynamics. Apart from decreasing the complications of positive pressure ventilation, early extubation is definitely associated with increased patient comfort and compliance.

Immunosuppressed post-LT recipients may also be particularly vulnerable to ventilator-associated pneumonia with prolonged ventilation. Prolonged mechanical ventilation may also increase right ventricular afterload and even induce venous congestion of the liver graft, especially in those with pre-existing tricuspid regurgitation and raised pulmonary artery pressures (which is not uncommon in end-stage liver disease patients). Furthermore, hepatic venous drainage is better in spontaneously breathing patients as it reduces intrapleural pressure, thereby increasing cardiac end-diastolic volume, which in turn increases cardiac output and hepatic blood flow. Improved donor graft circulation could aid in early liver graft recovery and regeneration.

In terms of cost effective practices, early extubation definitely scores higher as it decreases the cost incurred during the ICU stay, and also a reduced cost due to the shorter length of hospital stay. This improved utilization of resources is especially pertinent in developing nations with limited resources at their disposal. In a systematic review by Rando et al. [17] in 2011, practice of early extubation was shown to be associated with decreased ICU stay and overall shorter hospital stay, thereby decreasing the overall economic burden. It was therefore recommended that early extubation could be carefully applied in new programs, as it helps in reducing cost of ICU stay without subjecting the patients to increased risks. Similarly, Loh et al. [18] found a decrease in 2.5–3 days in the length of hospital stay following a fast tracking protocol post-LT, with significant savings in health care cost.

4 Anesthesia For Fast Tracking

Advances in balanced anesthesia techniques and monitoring systems allowing rapid arousal from anesthesia, like use of remifentanil (due to its rapid elimination), may aid in FT [19].

Some of the principles to guide anesthesia for FT include the following:

  1. (a)

    Balanced anesthesia using barbiturates/propofol combined with opioids at induction, followed by maintenance with inhalational agents along with narcotic infusion. Anesthesia is typically maintained with continuous infusion of rocuronium/cis-atracurium and fentanyl infusion with Isoflurane in air/O2 gas mixture.

  2. (b)

    Monitoring includes electrocardiography, pulse oximetry, invasive arterial pressure, central venous and advanced venous access, and continuous cardiac output monitoring.

  3. (c)

    Dose regulation of inhalational agents: requirements of various drugs, including inhalational agents decrease significantly during anhepatic phase. Similarly, higher MELD score is also associated with decreased requirement of inhalational agents.

  4. (d)

    Careful titration of anesthetic agents to prevent over dosage and delayed emergence. Bispectral index monitoring thereby plays a significant role in patients planned for early extubation.

  5. (e)

    Neuromuscular blockade using different NMDAs ranging from vecuronium and rocuronium to atracurium and cis-atracurium. Since, different NMDAs undergo variable hepatic metabolism, neuromuscular monitoring becomes an essential tool to monitor the degree of muscle strength prior to trial of extubation.

  6. (f)

    Adequate titration of the total dosage of opioids used in the perioperative period to ensure adequate analgesia and anesthetic depth, without causing excessive sedation and respiratory depression. Liver transplant recipients have reported to have reduced opioid requirement in the perioperative period when compared with patients undergoing other major abdominal surgeries. Another option is to use fentanyl-free periods intermittently during the surgery, instead of continuous fentanyl since it has a long context-sensitive time.

  7. (g)

    In possible candidates of immediate extubation, muscle relaxant and opioid infusion can be discontinued upon ensuring good flow on Doppler ultrasound on completion of all vascular anastomoses and adequate graft function. Prior to extubation, adequate hemostasis by the surgeon should be confirmed and required correction of abnormal TEG values, if any, should be ensured. Patients, thereafter, meeting the extubation criteria can be safely given a trial of immediate extubation.

5 Fast Tracking in the LDLT Setting

Most of the studies that have reported on feasibility and safety of fast tracking have been in the DDLT setting. There is a difference though between the DDLT and LDLT recipients. In adult-to-adult LDLT, the partial graft (right or left lobe) usually takes time to regenerate and attain optimal function. Higher incidence of vascular complications leading to re-exploration is a possibility owing to small size and stumps of vessels in the harvested graft. In addition, surgical duration, and consequently total anesthesia time for the recipient, is also more in LDLT compared to DDLT. Hence, experience with only a few cases of FT LDLT recipients has been published so far [10, 20, 21]. Bhangui et al. [21] reported successful extubation in OR in 15 LDLT recipients, which comprised only 2% of LDLTs performed during the study period, this confirms the difficulty in fast tracking LDLT recipients even in high volume, and experienced LDLT center. Fast-tracked patients were young, had a low BMI, most were CTP class A or B, had a low MELD score, METs’ score of 4–6, and no significant comorbidities. Also, most fast-tracked patients had no need for major BT. None of the patients in this subgroup required immediate re-intubation, all recovered well with short ICU and hospital stay and there were no major complications. Chae et al. [13] based upon a relatively large number of subset of LDLT recipients proposed preoperative psoas muscle index to positively correlate with successful immediate extubation.

LDLT is an opportunity for an “elective” procedure, hence adequate patient and donor preparation, as well as planning for immediate postoperative care is possible in the LDLT setting. Thus, experienced anesthesia teams in high volume LDLT centers should try and fast track more recipients in the near future.

6 Criteria For Fast Tracking

The search for ideal criteria for planned on table extubation, and fast tracking in the recipients is still on. Predetermined criteria could help streamline the perioperative course of the patients and increase the number of patients who can be given the trial of early extubation. Each institution has indeed defined criteria for patient selection based upon their unique patient profile, often influenced by their national selection policy for organ allocation.

However, in general, extubation criteria employed in various studies till date have broadly remained similar. Parameters used to assess the adequacy of neuromuscular reversal are - patient breathing spontaneously, awake, able to follow simple commands, respiratory rate ≤35 breaths/min, tidal volume ≥5 mL/kg and heart rate ≤20% above baseline.

Table 37.1 summarizes the various clinical criteria for operating room extubation after liver transplantation, as proposed by several authors.

7 Future Prospects

An optimal utilization of resources by reducing ICU and overall hospital stay, without any apparent increase in adverse effects as a direct consequence, should encourage more anesthetists to attempt fast tracking in a well selected group of recipients.

One of the arguments often stated for reluctance in adopting the concept fast tracking is the lack of evidence based on comparable patient data with different national policies in selection criteria of patients. As a consequence, results of these studies cannot be extrapolated to local institutions dealing with sicker or a different profile of patients.

Fast tracking can be viewed as a component of an enhanced recovery program after surgery (ERAS) but it lacks the definite end goals as described in different stages of ERAS program [12]. Thereby, the lack of required multimodal and multidisciplinary approach towards a common goal has been a hurdle in the wider acceptance of FT in LT. Incorporation of multidisciplinary team approach in the care of liver transplant recipients can be a step in the required direction. Different multispecialty teams should be involved in preoperative optimization of the patients with effective plan of care tailored to meet and address the uniqueness of each patient and their disease process. With the commitment on part of surgeons, anesthesiologists, and other disciplines, in conjunction with dynamic interactions between them at various stages of perioperative care can help us achieve the desired results.

Key Points

  • Fast tracking in liver transplantation is feasible and is cost effective.

  • Early extubation is one of the ingredients of fast tracking.

  • Possible fast tracking patients should be identified before transplantation.

  • There is a difference between DDLT and LDLT recipient for fast tracking as surgical duration much longer in LDLT.

  • There should be pre-defined criteria for extubating patient in operating theater.

  • Acute liver failure patient are ineligible for on table extubation.