BACKGROUND:Drug interactions involving immunosuppressants can compromise transplant outcomes. Although repeated ketamine administration induces hepatic enzymes in experimental models, clinical reports of induced clearance of cytochrome P450 (CYP) substrates are lacking. Continuous subcutaneous ketamine infusions are increasingly used for acute pain management. We present a case of difficult-to-maintain tacrolimus and sirolimus concentrations in the context of subcutaneous ketamine infusion for acute pain management. METHODS:A 55-year-old male heart transplant recipient received continuous subcutaneous ketamine (5.2-10.4 mg/h) for pain management following lower limb thrombectomy. Tacrolimus and sirolimus concentrations were monitored throughout hospitalization and rehabilitation. Population pharmacokinetic modeling with Bayesian estimation characterized temporal clearance changes, incorporating inter-occasion variability across six periods (pre-, during-, and weekly post-ketamine administration for 4 weeks). RESULTS:Following ketamine initiation, tacrolimus and sirolimus concentrations remained subtherapeutic despite dose escalations of 1.8-fold and 5-fold, respectively. Pharmacokinetic modeling revealed approximately 2-fold clearance increases during ketamine administration, peaking 1 week after initiation. Following ketamine discontinuation, tacrolimus and sirolimus concentrations progressively increased over 3 weeks, consistent with enzyme induction and recovery. Drug Interaction Probability Scale assessment indicated probable interaction (score + 5). Brief concomitant flucloxacillin use may have contributed to the observed changes. CONCLUSIONS:This case provides preliminary evidence of potential interaction between ketamine and CYP3A4-metabolized immunosuppressants. Clinicians should consider increased therapeutic drug monitoring when using ketamine with narrow therapeutic range medications, continuing approximately 3 weeks post-discontinuation.

Clinical trials in lung transplantation have been hindered by a lack of clarity on the formulation and significance of endpoints for evaluating therapeutic efficacy. To address this challenge, a multidisciplinary working group from the International Society for Heart and Lung Transplantation developed consensus recommendations on endpoints beyond mortality. These endpoints include primary graft dysfunction (PGD), chronic lung allograft dysfunction (CLAD), acute cellular rejection (ACR), antibody-mediated rejection (AMR), immunosuppression-related complications, patient-reported outcomes (PROs), and pediatric-specific considerations. For each endpoint, a subgroup reviewed measurement best practices, assessed links to clinical benefit, and evaluated the evidence supporting their utility in clinical trial settings. Consensus was established through a Delphi process involving three rounds of voting. This document provides practical guidance for operationalizing these endpoints and outlines their optimal use in clinical trials. By standardizing trial design, these recommendations aim to accelerate the development of urgently needed therapies to improve lung transplantation outcomes.

Most therapeutic advances in immunosuppression have occurred over the past few decades. Although modern strategies have been effective in reducing acute cellular rejection , excess immunosuppression comes at the price of toxicity, opportunistic infection , and malignancy . As our understanding of the immune system and allograft rejection becomes more nuanced, there is an opportunity to evolve immunosuppression protocols to optimize longer term outcomes while mitigating the deleterious effects of traditional protocols.

A multispecies outbreak of Nocardia occurred among heart transplant recipients (HTR), but not lung transplant recipients (LTR), in Sydney, New South Wales, Australia, during 2018-2019. We performed a retrospective review of 23 HTR and LTR who had Nocardia spp. infections during June 2015-March 2021, compared risk factors for Nocardia infection, and evaluated climate conditions before, during, and after the period of the 2018-2019 outbreak. Compared with LTR, HTR had a shorter median time from transplant to Nocardia diagnosis, higher prevalence of diabetes, greater use of induction immunosuppression with basiliximab, and increased rates of cellular rejection before Nocardia diagnosis. During the outbreak, Sydney experienced the lowest monthly precipitation and driest surface levels compared with time periods directly before and after the outbreak. Increased immunosuppression of HTR compared with LTR, coupled with extreme weather conditions during 2018-2019, may explain this outbreak of Nocardia infections in HTR.

Heart and lung procurements are multiphased processes often accompanied by an array of complex logistics. Approaches to donor evaluation and management, organ procurement, and organ preservation vary among individual procurement teams. Because early graft failure remains a major cause of mortality in contemporary thoracic organ transplant recipients, we sought to establish some standardization in the procurement process. This paper, in this vein, represents an international consensus statement on donor heart and lung procurement and is designed to serve as a guide for physicians, surgeons, and other providers who manage donors to best optimize the clinical status for the procurement of both heart and lungs for transplantation. Donation after brain death (DBD) and donation after circulatory determination death (referred to as donation after circulatory death [DCD] for the remainder of the paper) for both heart and lung transplantation will be discussed in this paper. Although the data available on DCD heart donation are limited, information regarding the surgical technique for procurement is included within this consensus statement. Furthermore, this paper will focus on adult DBD and DCD heart and lung procurement. Currently, no certification, which is either recognized and/or endorsed by the transplant community at large, exists for the training of a cardiothoracic procurement surgeon. Nevertheless, establishing a training curriculum and credentialing requirements are beyond the scope of this paper.

Introduction: The Medication Error Minimisation Scheme (MEMS) is a locally based ongoing multidisciplinary, multifaceted quality improvement (QI) project within an Australian adult tertiary level Intensive Care Unit (ICU). The project commenced in 2009. Its primary aim is to enhance medication safety within this ICU by utilising existing resources. The aim of this paper is to provide a descriptive account of the various activities, interventions and results of this project within the first three years.Methods: The research design for this project was based upon Plan-Do-Study-Act (PDSA) cycles associated with QI projects. Medication error rates and audits of: intravenous infusions, incompatible intravenous medications and incorrect documentation of withheld medications were analyzed according to simple statistical techniques. Initial and follow up medication safety surveys were compared using basic statistical analysis. Focus groups exploring barriers and enablers of medication incident reporting were analyzed according to qualitative techniques associated with focus group discussions. Other interventions included: regular education sessions; discussions within other departmental meetings such as nursing staff meetings and Morbidity and Mortality meetings; and bedside discussions and demonstrations. Promotion of medication safety occurred within a number of forums; activities and findings were advertised and displayed; a recognizable Logo for MEMS was employed; and incentives were provided for staff.Results: Reported Medication Incidents (MIs) increased from 6.2 to 14.9 MIs per 1000 patient days. Audits and chart reviews confirmed that more MIs are uncovered by employing a variety of techniques in addition to incident reporting. Staff surveys provided a rich source of information regarding medication safety. Audits of intravenous infusions revealed a reduced error rate from 38/331 (11.5%) to 15/468 (3.2%). Chart review of incorrect documentation of omitted medications decreased from 105/347 (30.3%) to 104/486 (21.4%). Focus groups provided information that was able to be used in a number of hospital forums in order to explain the impact of existing systems upon ICU staff.Conclusion: This ongoing QI project was able to achieve its targeted goals. The MI reporting rate was increased. This project demonstrated that measurable, "non-incident report" errors can be reduced by focusing upon and promoting medication safety in the ICU. These activities demonstrated a workplace that values medication safety, the discovery of shortfalls and the benefits of ongoing improvement. (C) 2012 Australian College of Critical Care Nurses Ltd. Published by Elsevier Australia (a division of Reed International Books Australia Pty Ltd). All rights reserved.