Begin typing your search above and press return to search.
EPUB Before Print

FULL TEXT

LETTER TO EDITOR
Role of Early Extubation After Orthotopic Liver Transplant

Dear Editor:

Traditionally, a period of mechanical ventilation (MV) in the intensive care unit (ICU) after orthotopic liver transplant (OLT) has been considered a standard of care, despite a decline in routine MV after major surgery.1 Over the past 3 decades, numerous studies have demonstrated the feasibility and safety of early liberation from MV after OLT, in both adult and pediatric patients, when the individual patient is deemed appropriate for such treatment, often as part of fast-track surgery.2-10

There is some debate as to whether early extubation should be defined as immediate extubation at the end of surgery or as extubation within 4 to 8 hours after surgery, with the suggestion that immediate postsurgery extubation may have a lower incidence rate for adverse events versus the rate associated with invasive ventilation for longer periods, eg, up to 6 to 9 hours postoperatively.5,6,11,12 However, although early extubation has been established as feasible and safe, questions remain with regard to specific outcome benefits that may foster the perception of fast-track extubation as necessary or desirable.13

The rationale for not undertaking early extubation includes, among other things, preemption of some known early postoperative pulmonary complications, diaphragmatic dysfunction, respiratory insufficiency secondary to pain, and the deleterious effects of unique lung-liver pathologies (eg, hepatopulmonary syndrome). Other potential concerns include hemod-ynamic instability, as well as major metabolic abnormalities, related to massive blood product transfusion, renal dysfunction, and the inherent nature of liver surgery.13,14 Furthermore, liver transplant patients are susceptible to neurological complications of their disease, which may necessitate prolonged duration airway protection.14 These potential complications are known to occur in patients with various preoperative physiological conditions and may coincide with other surgical complications of this major procedure.15

In contrast, the rationale for early extubation includes a desire to avoid the generic risks of ongoing MV, such as muscle deconditioning, ventilator-associated pneumonia, and increased mortality, as well as other specific complications.16 The theoretical effect of positive-pressure ventilation on hepatic function, as well as the improvement with spontaneous ventilation, is well described in the literature, although the effect on graft function has not been clearly established.17,18 One systematic review and meta-analysis has sug-gested a lower incidence of graft dysfunction for patients managed with early extubation compared with patients who received standard care (0.3% vs 3.8%, respectively; P < .01).19 Certainly, prolonged MV (>96 hours) is associated with a significant reduction in patient and graft survival, but this relationship will be impacted by the underlying complexity of those patients requiring prolonged MV and not a function of a simple linear association between MV duration and outcome.20 Furthermore, there are probable institutional benefits associated with early extubation versus conventional treatment.13,21

Bhatia and colleagues have recently explored the association of early extubation after OLT with postoperative vasopressor use and acute kidney injury.22 They reported a shorter duration of vasopressor requirement (0 vs 2 days, respectively; P < .01) and less need for renal replacement therapy (3% vs 21.2%, respectively; P = .05) in patients who received fast-track extubation (defined as extubation within 4 hours after the end of surgery) compared with patients who received conventional treatment. Acute kidney injury and renal replacement therapy requirement after OLT are associated with increased mortality, liver graft failure, and development of chronic kidney disease.23 As such, Bhatia and colleagues have earned commendation for their exploration of the association of postoperative MV and outcomes beyond those purely associated with respiratory or primary graft complications.

Patient-centered outcomes with regard to fast-track policies, including those associated with ventilatory management, are worthy of further study. Scoring systems may be useful to identify suitable patients for fast-track programs and particularly for early extubation after OLT.1,24 Similarly, another proposed area of focus in pediatric patients is the identification of the risk factors for requirement of prolonged MV after OLT.25 Identification of these patients and the relevant underlying factors is crucial to facilitate successful mitigation of the risks associated with prolonged MV. Another worthy point of concern is the negative effect of extubation failure and the requirement for reintubation, which is a predictor of poor outcomes, including lower respiratory tract infection, increased ICU length of stay, and mortality.26-28 A notable single-center study has suggested a stronger association with the risk of death for requirement for reintubation versus duration of MV, although the details of this comparison are complex and warrant further study.29

Within the context of a recent liver transplant, extubation failure represents a hazardous period for patient and graft. The subsequent hypoxemia can impede the oxygen delivery to the graft, which may be exacerbated by apnea during reintubation or by poor graft perfusion during any hemodynamic instability associated with induction of anesthesia. Furthermore, overzealous manual ventilation during an emergency reintubation may have a negative effect on graft perfusion.

There is marked variation in rates of reintubation in studies of fast-track extubation after OLT in adult patients. Rates of reintubation are as high as 15% for patients extubated within 8 hours of the end of surgery, similar to the typical expectation in the setting of a general ICU.5,30,31 Studies have reported a higher rate of required reintubation for patients extubated after 24 hours versus patients extubated within 24 hours, suggesting that reintubation requirements most often are associated with the original duration of MV and are a function of the complex postoperative factors that have mandated prolonged MV.3,4,13,32 Although less extensive than for broader population studies, the published data specific to the pediatric population suggest no increased rate of reintubation after early initial extubation.8,9 An optimal failure rate balances the potential gains of early liberation from MV versus the risks of doing so when, retrospectively at least, early extubation is not appropriate. Furthermore, an important goal is to establish a balance to benefit both the patient and the institution.33 A proposed optimal failure rate of 5% to 10% has been suggested to accommodate these varying concerns.26

Central to finding this balance is a clear understanding of the potential gains of early extubation. One retrospective comparative single-center cohort study demonstrated that enhanced recovery patients were extubated an average of 6 hours earlier than conventionally treated patients. Although the fast-track group did have lower rates of postoperative pulmonary complications, as well as reduced ICU lengths of stay, many patients in the conventional group would still meet many clinicians’ definition of early extubation.34 Similar differences in duration of MV have been shown in other groups, with similar reductions in length of stay and no differences in postoperative respiratory infections.35,36 Similar benefits with regard to length of stay, hemodynamic stability, transfusion rates, and infective complications have been reported in pediatric studies.9,10 Future studies similar to those of Bhatia and colleagues may reveal potential benefits of this approach, particularly those benefits that extend beyond pulmonary complications and length of stay, including important areas such as renal dysfunction.22

Studies that examine broader patient outcomes and that include the impact on other major organ complications, and not merely focusing on graft or respiratory dysfunction, are important to fully evaluating the role of early extubation after OLT. One recent meta-analysis of 15 studies in adult patients reported only 1 prospective study, and future research may increase this number.19 While efforts continue to identify those patients who are appropriate candidates for early extubation and other enhanced recovery procedures, it is important to consider likely specific benefits, for both patient and system, as well as any potential harms. This will enable the decisions regarding this element of care to be both evidence based and more specific to patients and disease. Additional high-quality evidence is required for both adult and pediatric liver transplant patients to enhance the notably few data reported for randomized controlled trials in this area. However, in the context of much of the recent work, these answers are perhaps more likely than ever to arrive soon, and future findings are eagerly anticipated.


References:

  1. Haque ME, Badenoch AD, Orlov D, Selzner M, McCluskey SA. Predicting early extubation after liver transplantation: external validation and improved generalizability of a proposed fast-track score. Transplantation. 2021;105(9):2029-2036. doi:10.1097/TP.0000000000003452
    CrossRef - PubMed
  2. Rossaint R, Slama K, Jaeger M, et al. Fluid restriction and early extubation for successful liver transplantation. Transplant Proc. 1990;22(4):1533-1534.
    CrossRef - PubMed
  3. Glanemann M, Langrehr J, Kaisers U, et al. Postoperative tracheal extubation after orthotopic liver transplantation. Acta Anaesthesiol Scand. 2001;45(3):333-339. doi:10.1034/j.1399-6576.2001.045003333.x
    CrossRef - PubMed
  4. Biancofiore G, Bindi ML, Romanelli AM, et al. Fast track in liver transplantation: 5 years’ experience. Eur J Anaesthesiol. 2005;22(8):584-590. doi:10.1017/s0265021505000980
    CrossRef - PubMed
  5. Mandell MS, Stoner TJ, Barnett R, et al. A multicenter evaluation of safety of early extubation in liver transplant recipients. Liver Transpl. 2007;13(11):1557-1563. doi:10.1002/lt.21263
    CrossRef - PubMed
  6. Mandell MS, Hang Y. Pro: early extubation after liver transplantation. J Cardiothorac Vasc Anesth. 2007;21(5):752-755. doi:10.1053/j.jvca.2007.07.009
    CrossRef - PubMed
  7. Ulukaya S, Arikan C, Aydogdu S, Ayanoglu HO, Tokat Y. Immediate tracheal extubation of pediatric liver transplant recipients in the operating room. Pediatr Transplant. 2003;7(5):381-384. doi:10.1034/j.1399-3046.2003.00072.x
    CrossRef - PubMed
  8. Fullington NM, Cauley RP, Potanos KM, et al. Immediate extubation after pediatric liver transplantation: a single-center experience. Liver Transpl. 2015;21(1):57-62. doi:10.1002/lt.24036
    CrossRef - PubMed
  9. Gurnaney HG, Cook-Sather SD, Shaked A, et al. Extubation in the operating room after pediatric liver transplant: a retrospective cohort study. Paediatr Anaesth. 2018;28(2):174-178. doi:10.1111/pan.13313
    CrossRef - PubMed
  10. Sahinturk H, Ozdemirkan A, Yilmaz O, et al. immediate tracheal extubation after pediatric liver transplantation. Exp Clin Transplant. 2018;10.6002/ect.2018.0067. doi:10.6002/ect.2018.0067
    CrossRef - PubMed
  11. Findlay JY, Jankowski CJ, Vasdev GM, et al. Fast track anesthesia for liver transplantation reduces postoperative ventilation time but not intensive care unit stay. Liver Transpl. 2002;8(8):670-675. doi:10.1053/jlts.2002.34678
    CrossRef - PubMed
  12. Steadman RH. Con: immediate extubation for liver transplantation. J Cardiothorac Vasc Anesth. 2007;21(5):756-757. doi:10.1053/j.jvca.2007.07.003
    CrossRef - PubMed
  13. Wu J, Rastogi V, Zheng SS. Clinical practice of early extubation after liver transplantation. Hepatobiliary Pancreat Dis Int. 2012;11(6):577-585. doi:10.1016/s1499-3872(12)60228-8
    CrossRef - PubMed
  14. Feltracco P, Carollo C, Barbieri S, Pettenuzzo T, Ori C. Early respiratory complications after liver transplantation. World J Gastroenterol. 2013;19(48):9271-9281. doi:10.3748/wjg.v19.i48.9271
    CrossRef - PubMed
  15. Altun GT, Dincer PC, Arslantas MK, Birtan D, Ayanoglu HO. Early postoperative complications of liver transplantation (Abstract). Transplantation. 2017;101:S36.
    CrossRef - PubMed
  16. Razonable RR, Findlay JY, O’Riordan A, et al. Critical care issues in patients after liver transplantation. Liver Transpl. 2011;17(5):511-527. doi:10.1002/lt.22291
    CrossRef - PubMed
  17. Kaisers U, Langrehr JM, Haack M, Mohnhaupt A, Neuhaus P, Rossaint R. Hepatic venous catheterization in patients undergoing positive end-expiratory pressure ventilation after OLT: technique and clinical impact. Clin Transplant. 1995;9(4):301-306.
    CrossRef - PubMed
  18. Saner FH, Olde Damink SW, Pavlakovic G, et al. Positive end-expiratory pressure induces liver congestion in living donor liver transplant patients: myth or fact. Transplantation. 2008;85(12):1863-1866. doi:10.1097/TP.0b013e31817754dc
    CrossRef - PubMed
  19. Li J, Wang C, Jiang Y, et al. Immediate versus conventional postoperative tracheal extubation for enhanced recovery after liver transplantation: IPTE versus CTE for enhanced recovery after liver transplantation. Medicine (Baltimore). 2018;97(45):e13082. doi:10.1097/MD.0000000000013082
    CrossRef - PubMed
  20. Yuan H, Tuttle-Newhall JE, Chawa V, et al. Prognostic impact of mechanical ventilation after liver transplantation: a national database study. Am J Surg. 2014;208(4):582-590. doi:10.1016/j.amjsurg.2014.06.004
    CrossRef - PubMed
  21. Aniskevich S, Pai SL. Fast track anesthesia for liver transplantation: review of the current practice. World J Hepatol. 2015;7(20):2303-2308. doi:10.4254/wjh.v7.i20.2303
    CrossRef - PubMed
  22. Bhatia R, Fabes J, Krzanicki D, Rahman S, Spiro M. Association between fast-track extubation after orthotopic liver transplant, postoperative vasopressor requirement, and acute kidney injury. Exp Clin Transplant. 2021;19(4):339-344. doi:10.6002/ect.2020.0422
    CrossRef - PubMed
  23. Thongprayoon C, Kaewput W, Thamcharoen N, et al. Incidence and impact of acute kidney injury after liver transplantation: a meta-analysis. J Clin Med. 2019;8(3):372. doi:10.3390/jcm8030372
    CrossRef - PubMed
  24. Bulatao IG, Heckman MG, Rawal B, et al. Avoiding stay in the intensive care unit after liver transplantation: a score to assign location of care. Am J Transplant. 2014;14(9):2088-2096. doi:10.1111/ajt.12796
    CrossRef - PubMed
  25. Sahinturk H, Kundakci A, Zeyneloglu P, Torgay A, Pirat A, Haberal M. Postoperative tracheal extubation after pediatric liver transplantation (Abstract). Transplantation. 2018;102:S860.
    CrossRef - PubMed
  26. Krinsley JS, Reddy PK, Iqbal A. What is the optimal rate of failed extubation? Crit Care. 2012;16:111. doi:10.1186/cc11185
    CrossRef - PubMed
  27. Chihara Y, Egawa H, Oga T, et al. Predictive factors for reintubation following noninvasive ventilation in patients with respiratory complications after living donor liver transplantation. PLoS One. 2013;8(12):e81417. doi:10.1371/journal.pone.0081417
    CrossRef - PubMed
  28. Annamalai A, Harada MY, Chen M, et al. Predictors of mortality in the critically ill cirrhotic patient: is the model for end-stage liver disease enough? J Am Coll Surg. 2017;224(3):276-282. doi:10.1016/j.jamcollsurg.2016.11.005
    CrossRef - PubMed
  29. Ragonete Dos Anjos Agostini AP, de Fatima Santana Boin I, Marques Tonella R, et al. Mortality predictors after liver transplant in the intensive care unit. Transplant Proc. 2018;50(5):1424-1427. doi:10.1016/j.transproceed.2018.02.087
    CrossRef - PubMed
  30. Ulukaya S, Ayanoglu HO, Acar L, Tokat Y, Kilic M. Immediate tracheal extubation of the liver transplant recipients in the operating room. Transplant Proc. 2002;34(8):3334-3335. doi:10.1016/s0041-1345(02)03670-9
    CrossRef - PubMed
  31. Thille AW, Harrois A, Schortgen F, Brun-Buisson C, Brochard L. Outcomes of extubation failure in medical intensive care unit patients. Crit Care Med. 2011;39(12):2612-2618. doi:10.1097/CCM.0b013e3182282a5a
    CrossRef - PubMed
  32. Biancofiore G, Romanelli AM, Bindi ML, et al. Very early tracheal extubation without predetermined criteria in a liver transplant recipient population. Liver Transpl. 2001;7(9):777-782. doi:10.1053/jlts.2001.23785
    CrossRef - PubMed
  33. Showstack J, Katz PP, Lake JR, et al. Resource utilization in liver transplantation: effects of patient characteristics and clinical practice. NIDDK Liver Transplantation Database Group. JAMA. 1999;281(15):1381-1386. doi:10.1001/jama.281.15.1381
    CrossRef - PubMed
  34. Xu Q, Zhu M, Li Z, et al. Enhanced recovery after surgery protocols in patients undergoing liver transplantation: a retrospective comparative cohort study. Int J Surg. 2020;78:108-112. doi:10.1016/j.ijsu.2020.03.081
    CrossRef - PubMed
  35. Brustia R, Monsel A, Conti F, et al. Enhanced recovery in liver transplantation: a feasibility study. World J Surg. 2019;43(1):230-241. doi:10.1007/s00268-018-4747-y
    CrossRef - PubMed
  36. King AB, Kensinger CD, Shi Y, et al. Intensive care unit enhanced recovery pathway for patients undergoing orthotopic liver transplants recipients: a prospective, observational study. Anesth Analg. 2018;126(5):1495-1503. doi:10.1213/ANE.0000000000002851
    CrossRef - PubMed


DOI : 10.6002/ect.2021.0281


PDF VIEW [85] KB.

From the Department of Anaesthesia, King’s College Hospital, London, United Kingdom
Acknowledgements: Benjamin Milne is a Specialty Trainee in Anaesthesia and Intensive Care Medicine and recipient of a National Institute of Health Research Academic Clinical Fellowship. Other than stated, the author has not received any funding or grants in support of the presented research or for the preparation of this work and has no declarations of potential conflicts of interest.
Corresponding author: Benjamin Milne, Department of Anaesthesia, King’s College Hospital, Denmark Hill, London, UK SE5 9RS
Phone: +44 20 3299 9000
E-mail: Benjamin.milne@kcl.ac.uk