Anesthetic concerns in recipients of hematopoietic stem cell transplant.

Abstract

Dear Editor, Since the advent of bone marrow transplant in 1957, our understanding of the biology behind Hematopoietic Stem Cell Transplant (HSCT) has improved[1] and almost 50,000 HSCT take place globally in a year.[2] Although anesthetic concerns of patients undergoing solid organ transplantation have been addressed, there is a dearth of literature relating to HSCT, especially after the recent advancements like targeted therapy.[3,4] HSCT entails the regeneration of different blood cell lineages from donor stem cells and embarks on the interplay between recipient T lymphocytes, natural killer (NK) cells and donor antigen presenting cells (APC) and lymphocytes. Allogenic transplant brings forth graft vs. tumor effect (GVT) which helps to prevent recurrences but is shadowed by the graft vs. host disease (GVHD), necessitating chronic immunosuppression. Post HSCT patients are at increased risk of opportunistic infections, especially before engraftment and subtle signs of infections may be missed in the preoperative period as well as there may be delayed wound healing after surgery. While exaggerated increase in host immunity may enhance GVHD, overt diminution by immunosuppressant may lead to secondary infections and reactivation of cytomegalovirus. Therefore, it is prudent to delay elective surgeries before engraftment and while the patient is on immune-modulators.[5] Moreover, anesthesiologist should be aware of long-term adverse effects of chemotherapeutic drugs including potential difficult airway due to gum hypertrophy (cyclosporine) and lymph node enlargement as part of post-transplant lymphoproliferative disorder (PTLD). Acute GVHD may involve different organ systems, leading to potentially dreaded complications like acute lung injury, veno-occlusive disease of liver, thrombotic micro angiopathy (TMA) which should be evaluated during the pre-anesthetic check-up.[5] Surgical stress leads to a temporary state of immunosuppression via various mechanisms like raised catecholamines, angiogenic factors, matrix metalloproteinases (MMPs) and attenuated NK cell activity and cell mediated immunity (CMI). Volatile agents, especially isoflurane may promote tumor growth and spread by reducing NK cell activity, T cell depletion, increased angiogenesis by up-regulation of hypoxia inducible factor (HIF-1 alpha), whereas N2O causes bone marrow suppression. However, sevoflurane was found to stabilize the anti-cancer gene P38. Similar to inhaled agents, ketamine and thiopentone induces T cell apoptosis and NK cell underactivity. Propofol appears to be beneficial by reducing angiogenesis and maintaining T cell activity. Despite report showing impairment of macrophage-monocyte function, midazolam appears to be safer. Action of muscle relaxants may get prolonged due to immunomodulators like cyclosporine, as seen in renal transplant recipients.[6] Although anecdotal reports showed that IV opioids reduced NK cell, T cell and TLR (Toll like Receptor) activity on macrophage, it might enhance tumor lysis by stabilizing P53 and P38 and induce tumor death via NF-kB (nuclear factor kappa beta) and Fas-FasL pathway. Thus, immunomodulating effects of opioids are dose and concentration dependent and judicial perioperative analgesia by opioids seems logical.[7] Whenever feasible, use of regional anesthesia must be emphasized as local anesthetics increase local NK cell activity. Propofol along with paravertebral block have been found to be associated with reducing tumor burden in ER-negative breast cancer. Specific concerns of immune-modulators are provided in Table 1 and perioperative concerns are summarized in Table 2.Table 1: Side effects of commonly used agents and their concernsTable 2: Perioperative concerns in a nutshellInduction by propofol/etomidate, followed by maintenance with total intravenous anesthesia (TIVA) with propofol, intermediate acting muscle relaxants with minimal organ dependent metabolism (e.g., atrcurium, cisatracurium) and use of regional anesthesia may be considered as preferred techniques of choice. With the growing number of HSCTs, the authors feel the need for renewed interest and good quality research in this area. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.