Dose-ranging effect of systemic diphenhydramine on postoperative quality of recovery after ambulatory laparoscopic surgery: a randomized, placebo-controlled, double-blinded, clinical trial.

STUDY OBJECTIVE: Diphenhydramine is an antihistamine with previously demonstrated analgesic and antiemetic properties. However, it is unknown if the beneficial perioperative properties of diphenhydramine can translate to a better quality of postsurgical recovery. The main objective of the current investigation was to investigate dose-ranging effects of diphenhydramine on quality of recovery after surgery. SETTING: Tertiary hospital in the United States. DESIGN: A prospective, randomized, double-blind trial. INTERVENTION: Saline, diphenhydramine 25 >mg, or diphenhydramine 50 mg given intravenously before induction. MEASUREMENTS: The primary outcome was global Quality of Recovery-40 at 24hours. Postoperative pain, nausea, opioid consumption, and discharge time were also evaluated. MAIN RESULTS: Ninety subjects were randomized, and 75 completed the study. The median (interquartile range) Quality of Recovery-40 scores were not different among study groups: 164 (151-189), 169 (159-181), and 172 (157-185) for the saline, 25-mg diphenhydramine, and 50-mg diphenhydramine groups, respectively (P=.74). Postoperative nausea was decreased in the 50-mg group, 3 of 24 (12.5%), compared with the saline group, 12 of 27 (44%), P=.01. There was an inverse linear association between postoperative opioid consumption and quality of recovery (R(2)=0.37, P<.001). CONCLUSIONS: Diphenhydramine does not provide dose-ranging improvements on postoperative quality of recovery after ambulatory laparoscopic gynecologic surgery. Our results support a recent concept that not all postoperative nausea and vomiting symptoms are clinically important. Future studies evaluating postoperative nausea and vomiting should include patient-centered outcomes to validate the clinical importance of the examined interventions.

Alemtuzumab induction and antibody-mediated rejection in kidney transplantation.

BACKGROUND: Induction therapy improves graft outcomes in kidney transplant recipients (KTRs). We aimed to compare the incidences of antibody-mediated rejection (AMR) and acute cellular rejection (ACR) as well as graft and patient outcomes in KTRs who underwent induction with alemtuzumab versus rabbit-antithymocyte globulin (r-ATG). METHODS: This was a single-center retrospective study involving patients who underwent kidney transplantation between January 2009 and December 2011 after receiving induction therapy with either alemtuzumab or r-ATG. Maintenance immunosuppression included tacrolimus and mycophenolate mofetil with early steroid withdrawal. Acute rejection was diagnosed using allograft biopsy. RESULTS: Among the 108 study patients, 68 received alemtuzumab and 40 got r-ATG. There was a significantly higher incidence of AMR (15% vs 2.5%; P = .008) and similar incidence of ACR (4.4% vs 10%; P = .69) for alemtuzumab versus r-ATG groups. One-year serum creatinine levels (l.68 ± 0.8 mg/dL vs 1.79 ± 1.8 mg/dL; P = .66) as well as graft (91.1 ± 3.5% vs 94.5 ± 3.8%; P = .48) and patient (93.8 ± 3.0% vs 96.4 ± 3.5%; P = .92) survivals were similar for the alemtuzumab versus the r-ATG groups. CONCLUSION: Our study showed a higher incidence of AMR and similar incidence of ACR in KTRs who underwent induction with alemtuzumab compared with those who received r-ATG and were maintained on tacrolimus and MMF. This was despite a lower HLA mismatch in the alemtuzumab group. One-year graft survival, patient survival, and allograft function were similar. Inadequate B-cell suppression by alemtuzumab as well as altered phenotypic and functional properties of repopulating B cells could be contributing to heightened risk of AMR in these patients.

Outcomes of paired-exchange live-donor kidney transplantation: a single-center experience.

INTRODUCTION: Paired-exchange kidney transplantation (PEKT) enables recipients with willing but incompatible donors to find potential matches from a larger pool of donors. It involves transportation of donor kidneys to the intended recipient with a consequent increase in the cold ischemia time (CIT). PATIENTS AND METHODS: Our single-center study compared the outcomes of PEKT versus traditional in-center live-donor kidney transplants (ICKT). Retrospective chart review of adult patients who underwent PEKT and ICKT from January 2009 to February 2012 at our institution was performed. Delayed graft function, acute rejection rates, incidence of proteinuria, trends in serum creatinine, and graft and patient survival rates were compared between groups. RESULTS: Baseline demographic data were similar between the PEKT group (n = 15) and the ICKT group (n = 30) except that CIT (13.1 vs 3.8 hours; P < .001) and panel reactive antibody titers (12.6% ± 22.9% vs 0.9% ± 4.9%; P = .01) were significantly higher in the PEKT group. No patient developed delayed graft function. At a median follow-up of 12.4 months (range: 2-27.5 months), graft and patient survival rates were 100% in both groups. Serial creatinine levels were similar between the groups. There were no significant differences between groups in acute rejection rates (3 of 15 vs 3 of 30) and development of proteinuria posttransplantation (8 of 15 vs 22 of 30). CONCLUSIONS: Our study found similar outcomes between the PEKT and ICKT groups despite longer CIT and higher panel reactive antibody titers in the PEKT group. These findings support the current practice of PEKT with transporting of donor kidneys, with the resultant increase in the chances of living-donor kidney transplantation.

Influence of steroid maintenance on the outcomes in deceased donor kidney transplant recipients experiencing delayed graft function.

Delayed graft function (DGF) is a risk factor for poor long-term graft and patient survival after kidney transplantation. The aim of our study was to explore the beneficial effect of steroid maintenance on outcomes in deceased donor kidney (DDK) transplant recipients with DGF. Using organ procurement and transplant network/United network of organ sharing (OPTN/UNOS) database, we identified adult patients who developed DGF following DDK transplantation performed between January 2000 and December 2008. They received induction with rabbit antithymocyte globulin (r-ATG), alemtuzumab or an interluekin-2 receptor blocker (IL-2B) and were discharged on a calcineurin inhibitor (CNI)/mycophenolate (MMF) based immunosuppression with or without steroids. Adjusted graft and patient survivals were compared between steroid versus no steroid groups for each induction modality. Median follow-up was 29.6 months for the 10,058 patients who developed DGF. There were 5624 patients in r-ATG (steroid, n = 4569, no steroid, n = 1055), 819 in alemtuzumab (steroid, n = 301, no steroid, n = 518) and 3615 in IL-2B (steroid, n = 3380, no steroid, n = 235) groups. Adjusted graft survivals were similar for steroid versus no-steroid groups in patients who received r-ATG (HR: 0.98, 95% CI 0.85-1.13, P = 0.75), alemtuzumab (HR 0.88, 95% CI 0.65-1.19, P = 0.41), and IL-2B (HR 1.01, 95%CI 0.78-1.30, P = 0.96) inductions. The adjusted patient survivals were also similar in r-ATG (HR: 1.19, 95% CI 0.96-1.46, P = 0.19), alemtuzumab (HR: 0.89, 95% CI: 0.57-1.39, P = 0.96), and IL-2R (HR: 1.07, 95% CI: 0.77-1.49, P = 0.96) groups. Our study failed to show any significant graft or patient survival benefits associated with steroid addition to CNI/MMF regimen in DDK recipients with DGF. This may be related to the early immunogenic and non-immunogenic allograft damage from DGF with long-term consequences that are unaltered by steroids.

Influence of maintenance steroids on the outcomes in deceased-donor kidney transplant recipients exposed to prolonged pretransplantation dialysis.

BACKGROUND: Pre-transplant dialysis duration exerts a graded negative influence on outcomes after kidney transplantation. Higher immune reactivity associated with prolonged dialysis with consequent increased acute rejection could be contributory. METHODS: Using the Organ Procurement and Transplant Network/United Network of Organ Sharing database, we identified patients ≥ 18 years of age who received deceased-donor kidney (DDK) transplants from 2000 to 2008 after being on maintenance dialysis for ≥ 4 years. Patients received induction therapy with rabbit antithymocyte globulin (r-ATG), alemtuzumab, or an interleukin-2 receptor blocker (IL-2B) and were discharged on calcineurin inhibitor (CNI)/mycophenolate mofetil (MMF)-based immunosuppression with or without steroid. Unadjusted and adjusted graft/patient survivals were compared in steroid versus no-steroid groups by induction type. RESULTS: A total of 14,459 patients were identified, of which 7,684 received r-ATG (steroid, 6,098; no-steroid, 1,586), 1,292 alemtuzumab (steroid, 362; no-steroid, 930), and 5,483 an IL-2B agent (steroid, 5,107; no-steroid, 376). Adjusted graft survivals were similar for steroid versus no-steroid groups in r-ATG (hazard ratio [HR] 1.10, 95% confidence interval (CI) 0.96-1.26, P = .16), alemtuzumab (HR 0.88, 95% CI 0.65-1.19; P = .40), and IL-2B (HR 0.91, 95% CI 0.73-1.13; P = .38) groups. Adjusted patient survival for steroid versus no-steroid groups was inferior in r-ATG (HR 1.41, 95% CI 1.17-1.71; P < .001) but similar in alemtuzumab (HR 1.05, 95% CI 0.70-1.59; P = .80) and IL-2B (HR 1.17, 95% CI 0.86-1.58; P = .32) groups. CONCLUSIONS: Our analysis failed to show a graft survival benefit for the addition of steroid to a CNI/MMF-based immunosuppression after induction with r-ATG, alemtuzumab, or an IL-2B agent in DDK recipients exposed to prolonged pretransplantation dialysis.

Effect of induction agent on posttransplant outcomes in deceased donor kidney transplant recipients: influence of race.

BACKGROUND: The effect of induction agents on kidney transplant outcomes with respect to race is not well studied. We aimed to compare the outcomes of deceased donor kidney (DDK) transplants in African American (AA) and non-African American (non-AA) recipients who underwent induction therapy with rabbit-antithymoglobulin (rATG), alemtuzumab (ALE), or interleukin (IL)-2 receptor blocker (IL-2B) and were maintained on a calcineurin inhibitor, (CNI)/mycophenolate mofetil (MMF)-based regimen with/without steroid. METHODS: Using OPTN/UNOS database, we identified patients (≥18 years) who underwent DDK transplants from January 2000 to December 2008 and received rATG (n = 21,506), ALE (n = 3476), or IL- 2B (n = 17,869) and were maintained on a CNI/MMF-based regimen with/without steroids. Multivariate analysis was performed adjusting for steroid use and factors known to adversely impact graft outcome. RESULTS: The median follow up was 29.6 months (range, 10.7-60.1). ALE induction as compared to rATG had inferior adjusted graft (P < .001) and patient (P = .003) survivals in non-AA recipients but similar in AA recipients. In non-AA recipients, IL-2 induction as compared with rATG had similar adjusted graft but inferior patient survival (P = .04), and in AA recipients had inferior graft (P = .002) but similar patient survival. CONCLUSION: Our study shows racial differences in renal transplant outcomes with regard to induction modality.

Kidney transplantation in hepatitis C-positive recipients: does type of induction influence outcomes?

BACKGROUND: Kidney transplantation in hepatitis C virus-seropositive (HCV+) recipients improves survival compared to staying on the waiting list. A concern for using depleting (versus nondepleting) induction agent during kidney transplantation in HCV+ recipients is the possibility that the associated enhanced immunosuppression might favor the progression of hepatitis C infection, leading to adverse outcomes. METHODS: Utilizing data from the Organ Procurement and Transplant Network, we identified HCV+ patients ≥ 18 years of age who underwent deceased donor kidney (DDK) transplants from either HCV+ or HCV- donors between 1998 and 2008. Patients were divided into two groups based on the induction type they received during the transplant: depleting agent (rabbit-antithymocyte globulin or alemtuzumab) or nondepleting agent (basiliximab or daclizumab) groups. Unadjusted and adjusted graft and patient survivals (Cox regression) between the groups were compared. RESULTS: A total of 3490 HCV+ DDK recipients were identified (1859 in the depleting and 1631 in the nondepleting groups). When compared to nondepleting agent, adjusted graft (hazard ratio [HR] 1.11, 95% confidence interval [CI] 0.96-1.28, P = .16) and patient (HR 1.15, 95% CI 0.93-1.42, P = .2) survivals were similar with depleting agent induction. HCV donor seropositivity did not adversely impact either graft (HR 1.11, 95% CI 0.96-1.29, P = .17) or patient (HR 1.15, 95% CI 0.93-1.42, P = .2) outcomes. CONCLUSIONS: Our analysis supports the practice of transplanting HCV+ donor kidneys into HCV+ recipients to alleviate waiting list burden. Recipient HCV positivity should not influence selection of induction agent.

Does delayed graft function in the first kidney transplant influence graft outcome in a subsequent transplant?

BACKGROUND: In kidney transplantation, delayed graft function (DGF) portends adverse graft and patient outcomes. It is unclear whether DGF in the first kidney transplant would adversely impact the outcome of a subsequent transplant. METHODS: Utilizing data from the Organ Procurement and Transplant Network, we identified patients ≥ 18 years of age who underwent at least two deceased donor kidney transplantation (DDKT) between 1987 and 2010. Patients were then divided into two groups based on whether or not they developed DGF in the first transplant (1st TXP DGF group and 1st TXP no-DGF group). Unadjusted and adjusted graft survivals (Cox regression) between the groups were compared. RESULTS: A total of 10,628 patients were identified who received more than one DDKT (3672 patients in the 1st TXP DGF group and 6956 patients in the 1st TXP no-DGF group). A higher incidence of DGF was observed with the second transplant in patients who had DGF in the first transplant (34% vs 26%, P = .001). Unadjusted graft survival for the second transplant was superior in the 1st TXP no-DGF group (P = .002). After correction for confounding variables, DGF in the first transplant did not have significant adverse impact on the graft survival of the second transplant (hazard ratio 1.2 with 95% confidence interval 0.96-1.09, P = .44). CONCLUSIONS: In patients undergoing more than one DDKT, DGF in the first transplant is associated with higher incidence of DGF in the subsequent transplant but did not have independent adverse influence on the outcome of that graft.

Dose ranging study on the effect of preoperative dexamethasone on postoperative quality of recovery and opioid consumption after ambulatory gynaecological surgery.

BACKGROUND: Glucocorticoids are commonly administered before ambulatory surgery, although their effects on quality of recovery are not well characterized. The purpose of this study was to evaluate the dose-dependent effects of dexamethasone on patient recovery using the Quality of Recovery 40 questionnaire (QoR-40) after ambulatory surgery. METHODS: This prospective, double-blind trial studied 106 female subjects undergoing outpatient gynaecological laparoscopy. Subjects were randomized to receive saline, dexamethasone 0.05 mg kg(-1) or dexamethasone 0.1 mg kg(-1) before induction. The primary outcome was global QoR-40 at 24 h. Postoperative pain, analgesic consumption, side-effects, and discharge time were also evaluated. RESULTS: Global median (IQR) QoR-40 after dexamethasone 0.1 mg kg(-1) 193 (192-195) was greater than dexamethasone 0.05 mg kg(-1) 179 (175-185) (P=0.004) or saline, 171 (160-182) (P<0.005). Median (IQR) morphine equivalents administered before discharge were 2.7 (0-6.3) mg after dexamethasone 0.1 mg kg(-1) compared with 5.3 (2.4-8.8) mg and 5.3 (2.7-7.8) mg after dexamethasone 0.05 mg kg(-1) and saline (P=0.02). Time to meet discharge criteria was 30 min shorter after dexamethasone 0.1 mg kg(-1) compared with saline (P=0.005). At 24 h, subjects receiving dexamethasone 0.1 mg kg(-1) had consumed less opioid analgesics, reported less sore throat, muscle pain, confusion, difficulty in falling asleep, and nausea compared with dexamethasone 0.05 mg kg(-1) and saline. CONCLUSIONS: Dexamethasone demonstrated dose-dependent effects on quality of recovery. Dexamethasone 0.1 mg kg(-1) reduced opioid consumption compared with dexamethasone 0.05 mg kg(-1), which may be beneficial for improving recovery after ambulatory gynaecological surgery.

When is it reasonable to split pediatric en bloc kidneys for transplantation into two adults?

BACKGROUND: Traditionally, kidneys from donors ≥60 years old and pediatric kidneys are considered marginal organs for transplantation. Pediatric donor kidneys are underutilized for transplantation into adult recipients due to concern for poor outcomes. METHODS: Using data from the Organ Procurement and Transplant Network, we analyzed patterns of pediatric kidney use (single vs en bloc) in the United States from 1987 to 2007. Using the Cox proportional hazards model, graft outcomes of pediatric donor kidneys transplanted as single vs en bloc grafts from different donor weight groups were compared with renal transplantation from donors ≥60 years old in an attempt to define a pediatric donor weight at which kidneys can be justifiably split to expand the donor pool. RESULTS: Compared with older donor kidneys, graft failure risk of pediatric single kidneys was consistently lower when the donor weight exceeded 10 kg. On the other hand, graft survival benefit for pediatric en bloc kidneys was evident starting at donor weight ≤10 kg in comparison to older donor kidneys. Pediatric en bloc kidneys performed consistently better than pediatric single kidneys for all donor weight groups. CONCLUSIONS: Splitting of pediatric donor en bloc kidneys for transplantation into 2 adults when the donor weight exceeds 10 kg was associated with acceptable graft outcomes. This practice, along with increased use of small pediatric donor kidneys, may help to alleviate the waiting list burden in renal transplantation.

Cardiac magnetic resonance imaging in hemodialysis patients.

BACKGROUND: The anatomy of left ventricular hypertrophy (LVH) in dialysis patients was studied with magnetic resonance imaging (MRI). Potential benefits of spironolactone were examined in a subset of patients. METHODS: This was a prospective case series of 30 hemodialysis patients in whom cardiac MRI was performed. Repeat MRI was done in a subset of 13 patients after 9 months of daily oral spironolactone 25 mg. RESULTS: Subjects exhibited a characteristic cardiac morphology, distinct from both concentric LVH (cLVH) and eccentric LVH (eLVH). Compared with normal controls, LV mass index was increased, end-diastolic volume index was increased, and ejection fraction was reduced, but sphericity indices did not differ. No significant changes were seen after spironolactone. CONCLUSIONS: LVH in dialysis patients has a unique MRI appearance which is distinct from either cLVH or eLVH, with profound LV thickening and moderate dilation of the ventricular cavity. A 9-month course of spironolactone therapy did not affect morphology.

Pulmonary embolism following successful thrombectomy of an arteriovenous dialysis fistula.

A hemodialysis patient was diagnosed with pulmonary embolism, shortly after successful thrombectomy of an autogenous arteriovenous fistula. Diagnostic testing revealed no alternative source for thromboembolism. Increased recognition of hypercoagulability as a common consequence of end-stage renal disease would suggest that dialysis patients would be at risk for thromboembolic events. A fully developed dialysis fistula may have sufficient luminal diameter to harbor subclinical or clinically significant venous thrombi. Clinicians should be alert to the possibility of venous emboli after fistula manipulation.

Renal replacement therapy in the critical care unit.

Acute renal failure is common in critically ill patients. Many intensive care unit patients require renal replacement therapy (RRT). Hemodialysis can be performed as intermittent treatments or as continuous RRT, which can be customized to clinical goals by the use of carefully designed replacement fluids and hemodialysates. The available forms of RRT are reviewed, with emphasis on the clinical indications that contribute to the choice and design of therapy. Practical issues and troubleshooting are discussed, as are available options for anticoagulation during RRT. Consideration is given to modality choice, hemodynamic issues, costs, and physiologic outcomes.

Safety of paracentesis in inpatients.

INTRODUCTION: Prior research has suggested that paracentesis is free from complications such as acute renal failure (ARF) providing albumin is administered. Actual safety of paracentesis > 1,000 ml was assessed at a tertiary care hospital. METHODS: 300 inpatient paracenteses performed between 12/99 and 4/04 were identified by coding records, of which 40 procedures were excluded due to lack of pre- or post-procedure lab values. Charts were reviewed for serum creatinine (Scr) before and after procedures, ascites volume, and clinical outcomes. RESULTS: 44 deaths occurred after 260 paracenteses (16.9%). Among 33 patients with ARF, 13 (39.4%) died. Only 31/227 patients without ARF (13.7%) died (p < 0.001). Serum creatinine (Scr) > 1.6 mg/dl prior to paracentesis predicted a 22.5% rate of ARF, compared to 8% for Scr < 1.0 (p = 0.002). ARF increased as volume increased (9.9%, 12.4%, and 14.9%, for volumes of < 2,300, 2,300 - 3,200, and > 3,200 ml) but this trend did not have statistical significance (p = 0.426). ARF occurred in 11/69 (15.9%) of patients receiving albumin, compared to 22/191 (11.5%) of patients who did not (p = 0.462). CONCLUSIONS: Paracentesis in inpatients has significant rates of ARF and death. Scr > 1.6 prior to paracentesis predicts an increased rate of ARF. Development of ARF is associated with an increased rate of death. No advantage was demonstrated with administration of albumin. Pre- and post-paracentesis labwork should be routine in inpatients.

Long-term outcomes of a fistula initiative: sustaining "fistula culture".

From 1998 to 2003, a low cost fistula initiative at Allegheny General Hospital increased the rate of AV fistulas from 32% to 72%. We present an additional 25 months of vascular access data, with stratification of results by gender and long-term patient survival data. These data show the self-sustaining nature of 'fistula culture' in an urban hemodialysis unit, and the survival benefits that result from increased fistula rates.

Collateralization of the palmar arch by a failing radiocephalic fistula: an underappreciated complication of Cimino fistula anatomy.

Stenosis at the anastomosis of an arteriovenous dialysis fistula can cause fistula failure due to venous thrombosis. Three cases are presented in which anastomotic stenosis in radiocephalic fistulas resulted in radial artery occlusion with collateralization of ulnar artery flow across the palmar arch. Hand ischemia did not occur, and reductions in fistula efficiency were clinically subtle. Urea kinetics were compromised, and a characteristic palmar bruit was heard.

The cost of steroid-free protocols in primary cadaver kidney transplantation.

Steroid-free immunosuppression regimens have been enjoying recent success in clinical transplantation. The use of antibodies required for such protocols can be an economic burden. We proposed to study their cost in our center. This retrospective study involved 147 consecutive patients subjected to 4 protocols of immunosuppression. The first received triple therapy. The second group received induction with basiliximab, whereas the third received Basiliximab plus cyclosporine (CSA) plus mycophenolate mofetil (MMF), and the fourth received Thymoglobulin plus CSA plus MMF in conjuction with only 4 days of steroid. Rejection episodes were treated with Solumedrol. Six-month charges were obtained from computerized records of the finance department, the in-house laboratories, and the transplantation service registry. All charges were expressed in 2004 dollars. Statistical analyses were obtained using chi-square, analysis of variance (ANOVA) and Kaplan-Meier tests. The 4 groups were similar with regard to donor and/or recipient gender, race, panel reactive antibodies, cold ischemia, dialysis requirements length of stay and readmission, graft survival, and function. Charges were significantly higher in the last 2 groups as compared with triple therapy.

AV fistula rates: changing the culture of vascular access.

PURPOSE: Data from the United States Renal Data System show about 30% of prevailing hemodialysis (HD) patients use arteriovenous fistulae (AVF), which falls far short of the Kidney Disease Outcomes Quality Initiative (K/DOQI) goals of 40-50%. Recent initiatives to increase the use of AVF in HD patients have been criticized as unachievable under realistic practice conditions. METHODS: A multidisciplinary effort to increase AVF use was undertaken at an outpatient HD center beginning in 1998. Strategies focused on education and recruitment of patients in both inpatient and outpatient settings, preservation of veins, pre-operative vein mapping, and education of staff. RESULTS: AVF rates increased from 32%, to 72% over 6 years. The percentage of prosthetic grafts decreased from 40% to 13%. Central venous catheters fell from 28% to 15%. Among residual patients with catheters, 77% had maturing fistulae, as well. Infection rates in the dialysis unit decreased by 39%. Bacteremia declined by 47%. These improvements have been sustainable over the past 12 months. CONCLUSIONS: Adherence to a strategic program similar to the Fistula First Initiative can increase fistula rates under ordinary practice conditions. High fistula rates can be achieved in male and female patients. Unanimous commitment among all members of the health care team is needed. Reduction in the risks of infection, bacteremia, endocarditis, and death may be derived from achievable changes in practice.