Use Of Induction Agents Research Articles

Spectrum of Pneumonia in Renal Transplant Recipients: An Indian Experience.

Respiratory tract infections are life-threatening infections in solid-organ transplant recipients that pose risk to the graft and to the patient. This study was undertaken to examine the clinical and microbiological spectrum of pneumonia in renal transplant recipients. Of 400 consecutive renal transplant recipients, 87 recipients (21.8%) were hospitalized between November 2014 and October 2016 with pneumonia. We examined demographic profiles and clinical investigations. The median age of patients was 38 years (range, 19-72 y). The mean time of presentation after renal transplant was 18 months (range, 1-174 mo). Most patients (80.5%) were on maintenance immunosuppression with tacrolimus, mycophenolate mofetil, and steroids; 34% of patients had an induction agent. Chronic hepatitis C and hepatitis B infections were found in 12.6% and 2.2% of patients, respectively, and new-onset diabetes in 19.5% of patients. Fever (88%), cough (87%), shortness of breath (68%), and hypotension (33%) were common presenting symptoms. Diarrhea was the most frequent accompanying symptom, found in 9.2% of patients. Cytopenia and graft dysfunction were present in 38.7% and 80.4% of patients. Among infections, fungal infections were the most frequent (30%) followed by mixed infections (20.7%), tuberculosis (12.6%), bacterial (12.6%), and viral (3.5%) infections. Etiology could not be found in 27.6% patients. Mortality rate was 24.1%, with the highest rates for fungal infections (44%), followed by bacterial (25%) and mixed infections (18%). Presence of hypoxia and hypotension at presentation was associated with increased risk of death, whereas use of induction agents, new-onset diabetes posttransplant, diabetes mellitus, and acute kidney injury were not correlated with death or increased duration of hospital stay. Pneumonia carries high risk of mortality in renal transplant recipients. Fungal and bacterial infections carry high risk of mortality. Despite invasive investigations, a substantial number of patients had unidentified etiology.

The Effect of Ketamine Versus Etomidate for Rapid Sequence Intubation on Maximum Sequential Organ Failure Assessment Score: A Randomized Clinical Trial

BackgroundThe use of induction agents for rapid sequence intubation (RSI) has been associated with hypotension in critically ill patients. Choice of induction agent may be important and the most commonly used agents are etomidate and ketamine. ObjectiveThis study aimed to compare the effects of a single dose of ketamine vs. etomidate for RSI on maximum Sequential Organ Failure Assessment (SOFA) score and incidence of hypotension. MethodsThis single-center, randomized, parallel-group trial compared the use of ketamine and etomidate for RSI in critically ill adult patients in the emergency department. The study was performed under Exception from Informed Consent. The primary outcome was the maximum SOFA score within 3 days of hospitalization. ResultsA total of 143 patients were enrolled in the trial, 70 in the ketamine group and 73 in the etomidate group. Maximum median SOFA score for the ketamine group was 6.5 (interquartile range [IQR] 5–9) vs. 7 (IQR 5–9) for etomidate with no significant difference (–0.2; 95% CI –1.4 to 1.1; p = 0.79). The incidence of post-intubation hypotension was 28% in the ketamine group vs. 26% in the etomidate group (difference 2%; 95% CI –13% to 17%). There were no significant differences in intensive care unit outcomes. Thirty-day mortality rate for the ketamine group was 11% (8 deaths) and for the etomidate group was 21% (15 deaths), which was not statistically different. ConclusionsThere were no significant differences in maximum SOFA score or post-intubation hypotension between critically ill adults receiving ketamine vs. etomidate for RSI.

#3770 EBV-NEGATIVE KIDNEY TRANSPLANT RECIPIENTS AND PTLD: THE IMPACT OF INDUCTION THERAPY

Abstract Background and Aims Individuals who are most susceptible to developing PTLD are those who are EBV-negative and receive organs from EBV-positive donors (EBV R-/D+). The evidence regarding the connection between ATG induction therapy and PTLD is inconsistent. No studies have specifically examined the relationship between ATG use and PTLD in subgroups of EBV-negative transplant recipients (EBV R-). Using the UNOS database, we studied the association between the use of induction agents and PTLD in EBV R- patients. Method We analyzed data from 2007 to 2022 of EBV R- patients who underwent their first kidney-only transplant and excluded those who received induction agents other than ATG, basiliximab, or alemtuzumab. We used logistic regression to evaluate the association between induction agents and PTLD. Results Of 20,531 recipients, 50.7% received ATG, 19.13% received basiliximab, 13.42% received alemtuzumab, and 16.75% received no induction. The overall PTLD incidence was 2.14%. ATG recipients had higher rates of deceased donor transplants, higher degree of HLA mismatch, longer dialysis vintage, and were less likely to be white, compared to non-ATG recipients. Multivariate analysis showed ATG recipients had a higher risk of PTLD compared to non-ATG (odds ratio = 1.47, p<0.001). After excluding recipients who did not receive induction, ATG remained a significant independent risk factor for PTLD when compared to recipients who received either basiliximab or alemtuzumab (odds ratio = 1.35, p = 0.007). There was no statistically significant difference in PTLD risk among patients treated with basiliximab, alemtuzumab, or no induction (refer to Table 1). Conclusion The use of ATG induction in EBV-negative kidney transplant recipients is associated with a higher risk of PTLD compared to basiliximab, alemtuzumab, and no induction. The risk of PTLD should be considered when choosing induction therapy for this patient population.

Clinical Perspectives towards Improving Risk Stratification Strategy for Renal Transplantation Outcomes in Indian Patients

Graft loss and rejections (acute/chronic) continue to remain important concerns in long-term outcomes in kidney transplant despite newer immunosuppressive regimens and increased use of induction agents. Global guidelines identify the risk factors and suggest a framework for management of patients at different risk levels for rejection; however, these are better applicable to deceased donor transplants. Their applicability in Indian scenario (predominantly live donor program) could be a matter of debate. Therefore, a panel of experts discussed the current clinical practice and adaptability of global recommendations to Indian settings. They also took a survey to define risk factors in kidney transplants and provide direction toward evidence- and clinical experience-based risk stratification for donor/recipient and transplant-related characteristics, with a focus on living donor transplantations. Several recipient related factors (dialysis, comorbidities, and age, donor-specific antibodies [DSAs]), donor-related factors (age, body mass index, type – living or deceased) and transplantation related factors (cold ischemia time [CIT], number of transplantations) were assessed. The experts suggested that immunological conflict should be avoided by performing cytotoxic cross match, flow cross match in all patients and DSA-(single antigen bead) whenever considered clinically relevant. HLA mismatches, presence of DSA, along with donor/recipient age, CIT, etc., were associated with increased risk of rejection. Furthermore, the panel agreed that the risk of rejection in living donor transplant is not dissimilar to deceased donor recipients. The experts also suggested that induction immunosuppression could be individualized based on the risk stratification.

Comparison of Clinical Outcomes of Induction Regimens in Patients Undergoing Liver Transplantation for Acute Liver Failure.

Spontaneous survival rates in acute liver failure (ALF) are vastly improved by liver transplantation (LT). However, the value of induction agents beyond steroids continues to be debated. To understand the potential benefit of different induction regimens in the ALF population, we compared overall survival of recipients undergoing LT in the United States for ALF. Using the Scientific Registry of Transplant Recipients, we assessed the impact of induction immunosuppression (IS) in a cohort of 3754 first-time LT recipients with a diagnosis of ALF from 2002 to 2018. Induction IS therapy was grouped into steroid-only induction, use of antithymocyte globulin (ATG), or interleukin 2 receptor antibody. Other regimens were excluded from analysis. Survival analysis was estimated via Cox proportional hazards models and expressed as hazard ratios (HRs). In LT for ALF, the use of induction agents beyond steroids is increasingly frequent over the last 2 decades. The use of ATG is associated with worse overall survival, even after adjusting for donor and recipient factors, with HR of 1.24 (95% confidence interval, 1.00-1.53; P = 0.05). An elevated serum creatinine, recipient and donor age, and Black ethnicity, were all associated with reduced survival, whereas maintenance IS with calcineurin inhibitors (CNIs) was associated with improved survival. Although adjunct induction therapy has become more common, our analysis shows that compared with a steroid-only induction regimen, the addition of ATG is associated with worse overall survival after LT for ALF. CNI maintenance was highly protective, suggesting that an IS strategy focusing on corticosteroid-only induction followed by CNI maintenance may offer the best overall survival rate.

Comparison of drugs used for intubation of pediatric trauma patients

PurposeRapid sequence intubation (RSI) drugs, such as propofol, affect clinical outcomes, but this has not been examined in the pediatric population. This descriptive study compares the outcomes associated with intubation drugs used in pediatric traumatic brain injury (TBI) patients. MethodsA retrospective chart review and descriptive analysis of intubated TBI patients, ages 0–17, admitted to Children's Hospital London Health Sciences Centre (LHSC) from January 2006–December 2016 was performed. ResultsOut of 259 patients intubated, complete data was available for 107 cases. Average injury severity score was 28; 46 were intubated at LHSC, 55 at primary care site, and 6 on scene. Intubation attempts were recorded in 87 of 107 paper charts. First-pass intubation success rate was 88.5%. Propofol (n = 21), midazolam (n = 31), etomidate (n = 13), and ketamine (n = 7) were the most commonly used intubation drugs. Paralytics were used in 50% of patients. Following use of propofol, Pediatric Adjusted Shock Index was increased as a result of worsening hypotension. Mean total hospital length of stay was 21 days with 7.5 days in ICU. Survival was 87%. ConclusionGreat variability exists in the use of induction agents and paralytics for RSI. Propofol was commonly used and is potentially associated with poorer clinical outcomes. Type of StudyRetrospective. Level of EvidenceIV

Rapid sequence induction (RSI) in trauma patients: Insights from healthcare providers.

We aimed to describe the current practice of emergency physicians and anaesthesiologists in the selection of drugs for rapid-sequence induction (RSI) among trauma patients. A prospective survey audit was conducted based on a self-administered questionnaire among two intubating specialties. The preferred type and dose of hypnotics, opioids, and muscle relaxants used for RSI in trauma patients were sought in the questionnaire. Data were compared for the use of induction agent, opioid use and muscle relaxant among stable and unstable trauma patients by the intubating specialties. A total of 102 participants were included; 47 were anaesthetists and 55 were emergency physicians. Propofol (74.5%) and Etomidate (50.0%) were the most frequently used induction agents. Significantly higher proportion of anesthesiologist used Propofol whereas, Etomidate was commonly used by emergency physicians in stable patients (P=0.001). Emergency physicians preferred Etomidate (63.6%) and Ketamine (20.0%) in unstable patients. The two groups were comparable for opioid use for stable patients. In unstable patients, use of opioid differed significantly by intubating specialties. The relation between rocuronium and suxamethonium use did change among the anaesthetists. Emergency physicians used more suxamethonium (55.6% vs. 27.7%, P=0.01) in stable as well as unstable (43.4 % vs. 27.7%, P=0.08) patients. There is variability in the use of drugs for RSI in trauma patients amongst emergency physicians and anaesthesiologists. There is a need to develop an RSI protocol using standardized types and dose of these agents to deliver an effective airway management for trauma patients.

Utility of induction agents in living donor kidney transplantation

Aim: The outcome and long-term adverse events associated with induction agent use for living donor (LD) kidney transplantation (KT) in India were studied. Materials and Methods: Consecutive LD kidney transplant recipients (KTRs) from 2005 to 2013 were studied. They were divided based on induction agent use, into induction group and no induction group. The induction group was further subdivided into those receiving antithymocyte globulin (ATG group) and those receiving basiliximab (IL-2RB group). Study subjects were also classified into high and low immunological risk groups. Outcomes evaluated were patient and graft survival, acute rejections, infections, leucopenia, malignancy, new-onset diabetes mellitus, antibody-mediated rejections, and 1-year serum creatinine. Results: Of 605 LD-KTRs, 445 (73.6%) received induction. 403 (90.6%) received basiliximab induction. There was significant improvement in patient and graft survival in induction group (log rank P = 0.041 and 0.024, respectively), but this benefit disappeared when adjusting for immunosuppressive regimen as well as when only patients on tacrolimus-mycophenolate (Tac-MPA) were considered. There was significant reduction in acute rejections, tuberculosis (TB), and BK viremia in the induction group even in patients receiving Tac-MPA. There was no significant difference between basiliximab and ATG except for increased risk of BK viremia with ATG. Conclusions: The use of induction agents is associated with reduced incidence of acute rejections and serious infections (TB and BK viremia). The survival benefit of induction agent use is lost with the Tac-MPA-based immunosuppression. Thus, induction agent use is not essential for better survival if using Tac-MPA-based regimen.

Effect of Donor-Recipient Age Match in Expanded Criteria Deceased Donor Kidney Transplantation

PurposeOur objective was to investigate the effects of age on patient and graft survival in expanded criteria donor (ECD) renal transplantation. MethodsBetween February 2000 and December 2015, we analyzed 405 deceased donor renal transplants, including 128 grafts (31.9%) from ECDs. Based on recipient age and ECD criteria classification, the recipients were divided into four groups: Group I, non-ECD to recipient age <50 years; Group II, non-ECD to recipient age ≥50 years; Group III, ECD to recipient age <50 years; and Group IV, ECD to recipient age ≥50 years. ResultsAmong the four groups, there were significant differences in baseline characteristics (age, body mass index [BMI], cause of end-stage renal disease [ESRD], number of kidney transplantations, and use of induction agent). The mean modification of diet in renal disease (MDRD) glomerular filtration rate (GFR) level at 1 month, 6 months, 1 year, 3 years, and 5 years after transplantation was significantly lower in patients with ECDs but MDRD GFR level at 7, 9, and 10 years did not differ significantly (P = .183, .041, and .388, respectively). There were no significant differences in graft survival (P = .400) and patient survival (P = .147). ConclusionOur result shows that, regardless of recipient age, kidney transplants donated by deceased ECDs have similar graft and patient survival.

A comparison of induction of labor success rates over three time periods in 20 years at a single academic tertiary care center: are we improving vaginal delivery rates?

Objective: To compare the rates of successful induction of labor during three one-year periods over 20 years at a single institution.Methods: All women at 37 weeks or beyond with a living, singleton, cephalic fetus admitted for induction of labor in 1992, 2002, and 2012 were included. The use of induction agents and rates of successful vaginal delivery were compared.Results: A total of 627 women were evaluated, 219 in 1992, 220 in 2002, and 188 in 2012. Various induction agents were employed over the 20 year period. However, the rates of successful vaginal deliveries did not significantly vary over the three time periods, 79.5% in 1992, 72.3% in 2002, 76.1% in 2012, p = .21. In subgroup analysis, no significant differences were found among women with one or more prior vaginal delivery, no prior vaginal delivery, or after excluding those with a prior cesarean section. In multiple variable logistic regression analysis, no induction agent besides amniotomy improved successful vaginal delivery rates.Conclusions: Despite the multiple induction agents available at our tertiary care institution over the past 20 years, we were unable to demonstrate any significant improvement in successful vaginal delivery rates after induction of labor.

Immunosuppression and Post-transplant Hyperglycemia.

Post-transplant diabetes mellitus is a significant risk factor for cardiovascular disease in solid organ transplantation. The main underlying pathophysiological mechanism of PTDM is pancreatic beta cell dysfunction in the context of insulin resistance, but the relative importance of each of these important components of glycemic metabolism is under intense debate. We searched MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials to January 15, 2015. We selected systematic reviews and meta-analyses and randomized clinical trials. When no such reports were found for a given topic or drug, observational studies were included in the assessment. There are agents with known diabetogenic effects: corticosteroids, calcineurin inhibitors including tacrolimus and cyclosporine, as well as the mammalian target of rapamycin inhibitors (sirolimus and everolimus). The association between the use of induction agents and PTDM is very scarce. No diabetogenic effects have been found with the use of azathioprine, mycophenolate mofetil and its derivatives. Immunosuppression is the major modifiable risk factor for development of PTDM but risk versus benefit analysis is required to balance risk of developing PTDM versus rejection. Caution is advisable in immunosuppressant adjustments in the event that PTDM develops based on current evidence. Physicians should choose and use immunosuppression regimens shown to have the best outcome for patient and graft survival, irrespective of PTDM risk.

Everolimus With Reduced Tacrolimus in Liver Transplantation

Everolimus With Reduced Tacrolimus in Liver Transplantation

The Registry of the International Society for Heart and Lung Transplantation: Fifteenth Pediatric Heart Transplantation Report—2012

The Registry of the International Society for Heart and Lung Transplantation: Fifteenth Pediatric Heart Transplantation Report—2012

Efficacy of Anti-Interleukin-2 Receptor Antibody in Reducing the Incidence of Acute Rejection After Renal Transplantation

Dear Editor, Acute rejection (AR) in kidney transplant recipients is a major risk factor for chronic allograft failure and reduction in early and long term mean graft survival. New immunosuppressant agents have been developed to reduce the incidence of these episodes (1). Immunobiological drugs such as monoclonal anti-interleukin-2 receptor antibodies have shown promise in this direction; they have a more restrict immunosuppressive effect, are not related to interleukin release syndrome and are related to lower rates of CMV infection than polyclonal antibodies (2). In his trial Saghafi et al. (3) showed a reduction of Biopsy-Proven Acute Rejection (BPAR) episodes in non-related living donor kidney transplant recipients performing anti-interleukin-2 receptor, daclizumab, as an induction drug in addition to standard therapy with cyclosporine, mycophenolate and prednisone. The induction group had a statistically significant (20.8%) reduction in rejection episodes compared to control group using only standard therapy after a six month follow up (3). Resembling data had already been shown in previous studies, Vincent et al. showed similar reduction in incidence of BPAR in low immunologic risk deceased donor kidney recipients and the same rate of bacterial infections and/or viral infections, including CMV, malignances and adverse event as placebo group (4). Another study showed a reduction in the incidence of BPAR in deceased and living kidney recipients of about 14 % in the group that underwent induction therapy with daclizumab with no increase in infections and adverse events (1). Saghafi et al. in accordance with other authors showed daclizumab as an effective induction treatment option for low immunologic risk living donor kidney recipients. However, missing data about safety drug profile such as incidence of infection, adverse events, CMV infection, and early and late cyclosporine trough levels are not reported in the text. There are several studies confirming that induction therapy with either monoclonal or polyclonal antibodies in addition to standard therapy reduces the incidence of acute rejection but none of these studies have shown statistically significant improving in long term graft survival. New trials such as ELITE-symphony (5) study performing inteleukin-2 receptor antibody as a calcineurin inhibitor sparing agent showed promising results when comparing classical treatment protocol with standard cyclosporine dose, mycophenolate and corticosteroids with daclizumab, corticosteroids and mycophenolate and low dose cyclosporine or low dose tacrolimus or low dose sirolimus. This study found better outcomes in term of lower incidence of acute rejection, adverse events, infections and a better allograft survival rates in daclizumab and low dose tacrolimus group (5). Improving long-term outcomes in renal transplantation is still a field of challenge and numbness but the use of induction agents in adjunction with other drugs for reducing their side effects is a promising strategy for better graft and patient survival. Perhaps, most important induction therapy importance is in minimizing exposure to other immunosuppressive therapy and its side effects and this topic deserves research.

Kidney and Pancreas Transplantation in the United States, 1999-2008: The Changing Face of Living Donation

The waiting list for kidney transplantation continued to grow between 1999 and 2008, from 41 177 to 76 089 candidates. However, active candidates represented the minority of this increase (36 951-50 624, a 37% change), while inactive candidates increased over 500% (4226-25 465). There were 5966 living donor (LD) and 10 551 deceased donor (DD) kidney transplants performed in 2008. The total number of pancreas transplants peaked at 1484 in 2004 and has declined to 1273. Although the number of LD transplants increased by 26% from 1999 to 2008, the total number peaked in 2004 at 6647 before declining 10% by 2008. The rate of LD transplantation continues to vary significantly as a function of demographic and geographic factors, including waiting time for DD transplant. Posttransplant survival remains excellent, and there appears to be greater use of induction agents and reduced use of corticosteroids in LD recipients. Significant changes occurred in the pediatric population, with a dramatic reduction in the use of LD organs after passage of the Share 35 rule. Many strategies have been adopted to reverse the decline in LD transplant rates for all age groups, including expansion of kidney paired donation, adoption of laparoscopic donor nephrectomy and use of incompatible LD.

199: Use of Induction Agents and Incidence of Infection and Malignancy Following Pediatric Heart Transplantation

Previously, induction use in pediatric heart transplant (HTx) recipients was associated with an increased lymphoma risk. This study reviewed the current era incidence and risks for infection and malignancy in pediatric patients (pts) induced with cytolytic agents or IL-2R antagonists.

Induction Therapy in Renal Transplantation

An overview of the past 10 years of clinical renal transplantation would include progress in the development of new induction protocols (non-depleting versus depleting monoclonal and polyclonal antibodies, plasmapheresis and intravenous immunoglobulins) designed to reduce the incidence and severity of rejection and adverse effects as well as improve long-term graft and patient survival. These modalities have been introduced primarily to reduce the incidence of acute rejection episodes leading to early graft loss, decrease the need for higher toxic doses of maintenance immunosuppressive drugs, such as calcineurin inhibitors, and possibly aid in the pursuit of the goal of achieving immunological tolerance and the avoidance of all long-term immunosuppressive therapy. What has resulted during the past 20 years as the use of induction agents has become more popular is the concurrent improvement in detection and treatment of acute and chronic infectious (primarily viral), and opportunistic and quasi-malignant disease accompanying the use of these agents and, therefore, their increase in popularity. However, the overall cost of therapy and the long-term results of protocols in which these agents have been used have not resulted in a definitive benefit thus far, because of the lack of sufficient numbers of defined randomised, long-term studies and the continuing introduction of newer protocols based on even more recent advances. The specific agents used for induction therapy to date, and the rationale for their introduction and mechanisms of action are discussed in this review.

The use of induction agents in liver transplantation

Purpose of review Despite improvements in early graft survival, late graft loss through chronic rejection and morbidity and mortality as a result of long-term treatment with immunosuppressive medications is a major concern. New drugs have facilitated new treatment protocols with the delayed or reduced application of calcineurin inhibitors or steroid avoidance. This review focuses on recent data concerning the use of induction agents in liver transplantation. Recent findings Clinical studies using induction agents have demonstrated their safety and efficacy, and show promise for a beneficial outcome in liver transplant patients. IL-2 receptor antibodies allow a reduction of maintenance immunosuppression and reduce side effects, such as diabetes or renal impairment. Several studies using IL-2 receptor antibodies have also shown a lower incidence of acute rejection episodes in paediatric patients. Thymoglobulin has been used primarily in hepatitis C-positive patients, and studies have shown a positive effect on virus replication without significant recurrence of hepatitis C. Alemtuzumab has shown promising results regarding acute rejection episodes and renal function in a low-dose calcineurin inhibitor protocol. Summary The use of induction agents in liver transplantation is a promising strategy to reduce acute rejection episodes, maintenance immunosuppression, and prevent side effects without affecting patient and graft survival.