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Background After primary maternal cytomegalovirus (CMV) infection during pregnancy, infants are at risk for disease. Methods Factors predictive of infant outcome were analyzed in a database of 304 pregnant women with primary infection. These women were enrolled between 2010 and 2017 and delivered 281 infants, of whom 108 were CMV infected. Long term follow-up occurred for 173 uninfected and 106 infected infants at age 4 years (range, 1–8 years). One hundred fifty-seven women were treated with an average of 2 doses (range, 1–6 doses) of high-dose hyperimmune globulin (HIG: 200 mg/kg/infusion). We used a regression model to define predictors of fetal infection, symptoms at birth, and long-term sequelae; 31 covariates were tested. Results Four factors predicted fetal infection: a 1.8-fold increase (30% vs 56%) in the rate of congenital infection without HIG (adjusted odds ratio [AOR], 5.2; P < .0001), a 1.8-fold increase (32% vs 56%) associated with maternal viral DNAemia prior to HIG administration (AOR, 3.0; P = .002), abnormal ultrasounds (AOR, 59; P = .0002), and diagnosis of maternal infection by seroconversion rather than avidity (AOR, 3.3; P = .007). Lack of HIG and abnormal ultrasounds also predicted symptoms (P = .001). Long-term sequelae were predicted by not receiving HIG (AOR, 13.2; P = .001), maternal infection in early gestation (odds ratio [OR], 0.9; P = .017), and abnormal ultrasounds (OR, 7.6; P < .003). Prevalence and copy/number of DNAemia declined after HIG. Conclusions Maternal viremia predicts fetal infection and neonatal outcome. This may help patient counseling. High-dose HIG may prevent fetal infection and disease and is associated with the resolution of DNAemia.

ESCULAPIO Project, funded by the Centre for Disease Prevention and Control (CCM) of the Italian Ministry of Health, for the program 2013, aims at increasing awareness on vaccine preventable infectious diseases (VPID) and vaccination in different targets of population and at spreading the culture of prevention by the development of information/training interventions on VPID. In Tuscany Region (Central Italy), educational courses on VPID in high schools were organized and students were stimulated to prepare informative materials on VPID for lower grade school pupils. Educational games for school pupils were realized in Liguria Region (Northern Italy) with the aim to increase awareness and knowledge of vaccination among primary school children, their families, and teachers. The Sicilian Operative Unit (OU) developed and validated a questionnaire to collect data on the main factors influencing vaccine uptake in a population from Southern Italy and spreading information on vaccines to the general population. Aim of the activities performed in Apulia Region (Southern Italy) was to collect, directly from the public, a set of issues to which people were more "sensitive," in order to perceive the dimension of informative needs and the misinformation in the field of vaccinations. A toll-free telephone line to answer questions on VPID was also the aim of the Apulian activities. The objective of the OU of Sardinia (Southern Italy) was to increase knowledge on VPID and adherence to immunization campaigns in health care workers (HCW) by realizing traditional and e-learning training courses and initiatives of health promotion in healthcare and hospital setting. Interventions to promote vaccinations in maternal and child health services and outreach interventions in case of parental non-compliance with vaccination schedules were performed in the Veneto Region (Northern Italy), with the aim to reach a particular subgroup of the general population: new or future parents. The activities of Veneto Region aimed also at realizing individual interviews with parents and/or home visit, if considered useful, for families not respondents to the active ordinary call.

Introduction The BMT-CTN 1204 study for Hemophagocytic Syndromes or Selected Primary Immune Deficiencies (NCT01998633) (RICHI) was a single arm study testing safety and efficacy of reduced intensity conditioning (RIC) with alemtuzumab (1mg/kg), fludarabine (150 mg/m2) and melphalan (140 mg/m2). Survival was favorable compared to historical studies, but patients experienced high rates of mixed chimerism (MC) and ultimate secondary graft failure (GF). Mechanisms for GF are not known. Expansion of recipient T cells and interferon-gamma pathway activation have been proposed as drivers for GF. However, high peri-transplant alemtuzumab levels have been associated with higher risk of MC and eventual secondary GF, suggesting an inverse relationship between GF and immune activation in the context of RIC. In order to elucidate mechanisms of GF for patients on the RICHI study, we systematically evaluated cytokine patterns and alemtuzumab levels and their association with durable engraftment. Methods Serial blood samples were collected, processed, and stored for consenting patients at day -14 (window: day -28 to -14), day -7 (+/- 1 day), day -1 (+/- 1), day +1 (+1 to +3), day +14 (+/- 2), day +28 (+/- 2), day +42 (+/- 3), day +70 (+/- 10), and day +100 (+/- 10). Alemtuzumab levels were measured using a flow cytometric assay as previously described. Comprehensive cytokine analysis was performed for over 100 analytes using the MagPix platform. Primary GF was defined as donor chimerism Results Thirty-three patients were included in this study with HLH (n=25), CAEBV (n=3), CGD (n=2), HIGM (n=2), and IPEX (n=1). All patients received bone marrow grafts and 27 (82%) patients had unrelated donors. Twenty-one grafts were 8/8 or 6/6 HLA-matched (64%) and 12 grafts were 7/8 HLA-matched (36%). Among all patients, 1 patient (3%) developed primary GF, 22 (67%) developed mixed chimerism (MC), and 11 patients (33%) developed secondary GF. Survival with sustained engraftment without DLI or second HCT was 40.0%. We first evaluated peripheral blood levels of 100+ cytokines. Analysis revealed significant differences between patients with and without GF as shown in Figure 1A. Notably, on day +14 and +28, patients with secondary GF had significantly lower CXCL9 levels than those without GF. We then estimated the cumulative incidence (CI) of secondary GF among patients with CXCL9 levels above and below the day +14 median level of 2394pg/mL. The CI of secondary GF in patients with a day +14 CXCL9 level ≤2394pg/mL was 73.6% vs 0% in patients with a level >2394pg/mL (p=0.002). The CI of secondary GF in patients with a day +28 CXCL9 level ≤2867pg/mL (day +28 median) was 64.3%, vs 0% in patients with levels >2867pg/mL (p=0.004). We then sought to correlate CXCL9 levels with alemtuzumab exposure, as high alemtuzumab levels would result in more efficient T cell depletion of donor grafts that could lead to lower CXCL9 levels. Indeed, CXCL9 levels inversely correlated with day 0 alemtuzumab levels. Patients with day 0 alemtuzumab levels >0.32µg/mL had lower CXCL9 levels compared to patients with levels ≤0.32µg/mL (Figure 1B). Finally, we examined the impact of alemtuzumab levels on MC and secondary GF. Patients with day 0 alemtuzumab levels ≤0.32µg/mL had a lower CI of MC compared to patients with levels >0.32µg/mL, 14.3% vs 90.9%, respectively (p=0.03). The CI of secondary GF was 0% in patients with day 0 alemtuzumab levels ≤0.32µg/mL compared to 54.3% in patients with levels >0.32µg/mL (p=0.08). Conclusions This study demonstrates a strong relationship between alemtuzumab levels and durable engraftment. Further, interferon gamma activity, as reflected by CXCL9, inversely correlates with peri-transplant alemtuzumab levels in this prospective cohort treated with RIC. Our findings support the paradigm that higher alemtuzumab levels drive efficient T cell depletion of the stem cell product which increases the risk of MC and secondary GF, suggesting that donor T cells promote engraftment via a graft versus hematopoiesis function. Precision alemtuzumab dosing strategies may offer an opportunity to improve outcomes for patients who undergo RIC HCT. Figure 1 Figure 1. Disclosures Pulsipher: Adaptive: Research Funding; Equillium: Membership on an entity's Board of Directors or advisory committees; Jasper Therapeutics: Honoraria. Bollard: Neximmune: Current equity holder in publicly-traded company; Catamaran Bio: Membership on an entity's Board of Directors or advisory committees; Cabaletta Bio: Current equity holder in publicly-traded company, Membership on an entity's Board of Directors or advisory committees; Mana Therapeutics: Current equity holder in publicly-traded company, Membership on an entity's Board of Directors or advisory committees, Patents & Royalties; Cellectis: Honoraria, Membership on an entity's Board of Directors or advisory committees; Repertoire Immune Medicines: Current equity holder in publicly-traded company; ROCHE: Consultancy, Honoraria; SOBI: Honoraria, Membership on an entity's Board of Directors or advisory committees. Kean: Regeneron: Research Funding; Bristol Myers Squibb: Patents & Royalties: From clinical trial data, Research Funding; Bluebird Bio: Research Funding; Gilead: Research Funding; Vertex: Consultancy; Novartis: Consultancy; EMD Serono: Consultancy. Jordan: Sobi: Consultancy. Allen: Sobi: Consultancy. OffLabel Disclosure: Alemtuzumab, humanized monoclonal antibody against CD52, used as part of allogeneic HCT conditioning

Introduction Congenital dyserythropoietic anemias (CDA) are a rare group of hereditary disorders characterized by anemia, ineffective erythropoiesis, and secondary hemochromatosis. While some CDA patients respond to interferon α therapy (type I CDA) or splenectomy (type II CDA), others are dependent on chronic red cell transfusions lifelong. Hematopoietic cell transplant (HCT), remains the only curative option for this disease. In 39 patients reviewed by the European Society for Blood and Marrow Transplant (EBMT), graft rejection (GR) was 12% (1-23%), the 3-year overall survival (OS) and event free survival (EFS) were 71% (55-87%) and 45% (45-63%) respectively1. A trend towards higher incidence of GR and severe (Grade III-IV) acute graft versus host disease (GvHD) was observed in patients with iron overload and unrelated donor HCT but these risk factors were not statistically significant1. We report the outcomes in 17 children with CDA who underwent HCT at participating Pediatric Transplantation and Cellular Therapy Consortium (PTCTC) centers. Methods Clinical information on transplant and associated outcomes were collected retrospectively after IRB approval using a common questionnaire. Data were analyzed using descriptive statistics. Comparisons between groups were made using Fisher's exact tests. Survival estimates and corresponding 95% confidence intervals were performed using the Kaplan-Meier method. Results Seventeen patients (11 males) with CDA were eligible by diagnosis and underwent HCT from 2002-2019. The median age at diagnosis was 0.7 (range: 0.2 - 14) years. A majority (n=12) of patients had CDA type II while the remainder either had CDA type I (n=2) or were unknown (n=3). Twelve (71%) patients had evidence of iron overload by biopsy or imaging and 11 received pre-HCT chelation. Three of the 12 patients had liver fibrosis confirmed by biopsy. Thirteen patients had splenomegaly and four underwent splenectomy prior to HCT. Three patients received pre-HCT immunosuppressive therapy (PTIS). Median age at the time of HCT was 5.5 (range: 0.7 - 15) years. The median interval between diagnosis and HCT was 3.8 (range 0 - 12.3) years. Most patients received myeloablative busulfan-based conditioning (n=12); however, 5 patients received nonmyeloablative (n=1) or reduced intensity (n=4) fludarabine-based conditioning regimens. Donor sources included HLA matched sibling (n=3), matched unrelated (n=9), haploidentical (n=1) and mismatched unrelated (n=4) donors. Graft source was bone marrow in all but 2 patients who received umbilical cord blood. The median total nucleated cell (TNC) dose for bone marrow grafts was 6.0 (range: 3.4- 20.6) x 108/kg. Cord blood recipients received a TNC dose of 3.8 x 107 and 4.8 x 107/kg. Five (29%) patients developed acute GvHD grade II-IV, with one patient with grade III-IV acute GvHD (5.8%). Post-HCT complications included veno-occlusive disease (n=3), acute kidney injury (n=1), congestive cardiac failure (n=1), thrombotic microangiopathy (n=1), CMV viremia requiring therapy (n=2), mucormycosis (n=1), streptococcal pneumonia (n=1), recurrent clostridium difficle colitis (n=1), and parvovirus infection (n=1). Four patients developed chronic GvHD (23.5%; 2 limited and 2 extensive). Characteristics and outcomes of the four patients (23.5%) who developed GR are shown in Table 1. With a median follow-up of 3.4 (range: 0.08 - 14) years; fourteen patients are alive. Three patients died from respiratory failure due to adenovirus, congestive cardiac failure and extensive chronic GvHD post 2nd HCT. The 2-year OS, EFS and GvHD-free-rejection-free survival of the entire cohort (95% confidence interval) were 87% (72-100%), 64% (44 -92%), and 58% (39- 88%), respectively (Figure 1). Due to limited sample size, we did not find any patient or HCT-related factors that were associated with GR, OS or GvHD. Conclusion HCT can be curative for patients with CDA. The incidence of GR and GvHD in our CDA cohort was comparable to the recent EBMT report1. Strategies such as aggressive chelation, use of PTIS and perhaps early HCT in the presence of a suitable donor before co-morbidities occur are needed to improve engraftment without increasing risk for toxicities and mortality. Not unexpectedly we observed considerable morbidities in patients who had GR and required a 2nd HCT. Disclosures Pulsipher: Novartis: Honoraria; Bellicum: Honoraria; Jasper: Honoraria; Mesoblast: Honoraria; Miltenyi: Honoraria, Research Funding; Adaptive: Research Funding.

We developed a haploidentical transplantation protocol with post-transplant cyclophosphamide (CY) for in vivo T-cell depletion using a novel adapted-dosing schedule (25 mg/kg on days +3 and +4) for Fanconi Anemia. With median follow-up of 3 years (range, 37 days to 6.2 years), all six patients engrafted. Two patients with multiple co-morbidities and late referrals to transplant died from sepsis (n=2) and chronic graft-versus-host disease (GVHD) (n=1). Four patients without pre-existing co-morbidities and early transplant referrals are alive with 100% donor chimerism and excellent performance status. We conclude that modulated-dosing post-transplant CY is effective in vivo T-cell depletion to promote full donor engraftment in patients with Fanconi anemia.

Background Identification of intensive care unit (ICU) patients who require nutrition intervention is crucial to initiating nutrition therapy. This prospective quality improvement study evaluated the Nutritional Risk Screening (NRS) 2002, Malnutrition Universal Screening Tool (MUST), and Nutrition Risk in Critically Ill (NUTRIC) score in comparison with the Veterans Administration Nutrition Status Classification (VANSC) tool to determine which best identified the need for nutrition intervention. Methods A convenience sample of 150 ICU patients was evaluated using the VANSC, NRS 2002, MUST, and the NUTRIC score. The resultant score, need for nutrition intervention, and presence of malnutrition were recorded for patients. Interventions were defined as need for enteral or parenteral nutrition, nutritional supplements, or diet change. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), Matthews Correlation Coefficient (MCC), F1 score, and accuracy to predict need for nutrition intervention were calculated for each screening tool. Results Of the 150 patients, 49 (33%) required 1 or more nutrition interventions. The NRS 2002 (0.878) and VANSC (0.816) had the highest sensitivity. The NUTRIC (0.921) and VANSC (0.911) had the highest specificity. The VANSC (0.816) and MUST (0.687) had the highest PPV. The VANSC (0.911) and NRS 2002 (0.872) had the highest NPV. The VANSC (0.727) and MUST (0.528) had the highest MCC. The VANSC (0.816) and MUST (0.680) had the highest F1 score. Conclusions Trialing several tools to identify their efficacy and reliability individual setting may help determine the most appropriate tool to utilize for your patient population and specific goals.

Background: Allogeneic hematopoietic stem cell transplantation (HSCT) is a potentially curative therapy for pediatric patients with hematologic malignancies. Historically, matched sibling donors (MSD) have been the preferred donor source given ease of availability and lower rates of graft-versus-host-disease (GVHD). However, only 30% of patients have a MSD and relapse rates are high after MSD HSCT, raising the question of best donor choice. As conditioning regimens evolve, GVHD management improves and supportive care advances, it is important to evaluate the role of donor source on short and long-term clinical outcomes to inform donor selection. We performed a single-center retrospective analysis comparing post-HSCT outcomes in a cohort of pediatric patients undergoing MSD, matched unrelated donor (MUD), and umbilical cord blood (CB) transplants from 2006 to 2018. Methods: A retrospective analysis was performed on an IRB-approved protocol through Fred Hutchinson Cancer Research Center. 232 patients were included who received MSD (n=56), MUD (n=89) or CB (n=87) transplants. Of note, 24 CB patients received expanded CB cells in addition to unmanipulated unit(s). GVHD prophylaxis in all patients consisted of a calcineurin inhibitor and MMF or methotrexate. The vast majority received a high-intensity conditioning regimen (86%, 96%, and 82% respectively for MSD, MUD and CB). Overall survival (OS) and disease-free survival (DFS) were evaluated using the Kaplan-Meier method. Probabilities of non-relapse mortality (NRM), relapse, and acute GVHD were evaluated using cumulative incidence (CI) estimates with appropriate competing risks. The Cox regression model was used for adjusted analysis for age, year of transplant, sex, CMV status, MRD status, disease risk, and conditioning regimen. Results: Patient/treatment/donor demographics are shown in Table 1. Median follow-up was 2.6, 3.7 and 3.1 years for MSD, MUD and CB respectively. Patient diagnosis, disease risk, gender, age, and CMV serology were balanced between groups. CI of engraftment was similar as well, with only one graft failure in the MUD group (Fig 1). Median time to platelet recovery was significantly faster in MUD and MSD groups as compared to the CB group (p Conclusions: Our data demonstrate no difference in unadjusted OS between MSD, MUD and CB recipients. Importantly, despite this equivalence, 5-year DFS was significantly better in the CB v. MSD group, reflecting the lower relapse rate observed in CB patients and seen previously by us and others. CB continues to be viewed as an "alternative" donor for HSCT due to the low stem cell dose in a CB graft resulting in delayed neutrophil recovery, primary graft failure and increased NRM. However, this was not observed herein, supporting the use of CB for pediatric HSCT perhaps especially in patients at high risk of post-transplant relapse. Disclosures Milano: ExCellThera: Research Funding; Amgen: Research Funding. Delaney:Nohla Therapeutics: Employment, Equity Ownership; Biolife Solutions: Membership on an entity's Board of Directors or advisory committees. Bleakley:HighPass Biotherapeutics: Equity Ownership, Membership on an entity's Board of Directors or advisory committees, Patents & Royalties, Research Funding.

For decades, it has remained challenging to achieve long-term engraftment and correction of blood counts using gene-modified hematopoietic stem cells for Fanconi anemia. Toward this goal, our group conducted preclinical studies using a safety modified lentiviral vector encoding full-length cDNA for FANCA in normal and affected patient hematopoietic progenitor cells, and in a mutant mouse model that supported the IND for a gene therapy clinical trial for Fanconi anemia, complementation group A (NCT01331018). These studies led us to incorporate methods such as addition of N-acetylcysteine and hypoxic incubation during transduction. Because of the low stem cell numbers of Fanconi patients and initial difficulty with using plerixafor off-label for mobilization, we began our study with bone marrow as the source of stem cells. Due to concerns regarding secondary cancers, no conditioning was administered prior to infusion of gene-modified cells. The US Food and Drug Administration approved adult patients initially, but later permitted pediatric patient enrollment with a minimum age of 4 years. The primary objective of our phase I trial was safety. Secondary objectives included in vitro correction of mitomycin C (MMC) sensitivity, procurement of sufficient cell numbers, and ultimately, long-term correction of blood counts in recipients. Eligibility included absolute neutrophil count ≥0.5, hemoglobin ≥8, platelet count ≥20,000, lack of matched family donor, adequate organ function, and not meeting criteria for diagnosis of MDS. Our three enrolled patients were ages 22, 10, and 5 years. All demonstrated defects in the FANCA gene, with two patients sequenced and one patient diagnosed by complementation. Due to in-process learning and the later addition of plerixafor mobilization to the protocol, three different laboratory procedures were used to prepare the gene-modified product for each patient. Cell products were CD34+ selected bone marrow, bone marrow mononuclear cells depleted of red cells by hetastarch, and G-CSF and plerixafor mobilized cells depleted of red blood cells and cells bearing lineage markers, respectively. Transduction efficiencies were 17.7, 42.7 and 26.3% of colony forming cells (CFC) in 0 nM MMC, and 80, 100, and 100% of CFC in 10 nM MMC. Growth of hematopoietic colonies in MMC indicated functional correction of the FANCA defect. The 1st patient received 6.1×10e4, the 2nd 2.9×10e5, and the 3rd 4.3×10e6 CD34+ cells/kg. Serious adverse events included cytopenias in all patients, and hospital admission for fever due to viral upper respiratory infection in one patient. The patients remain alive at 46, 38, and 12 months after receipt of gene-modified cells. Due to worsening cytopenias, the third patient underwent hematopoietic cell transplant from an unrelated donor 10 months after infusion of gene-modified cells. To date, he has done well with transplant, and no indication that prior gene therapy impacted the outcome. The blood counts for the first 2 patients who have not undergone allogeneic transplant remain stable at 1,111 and 1,077 days post infusion compared to the first blood counts when they arrived at our center. For the 1st patient, vector was detectable in white blood cells (WBC) up to 21 days, in the 2nd up to 582 days, and the 3rd up to 81 days post infusion. Thus, in these patients, despite dramatic improvement in cell dose during the study, there was lack of persistence in detection of gene-modified WBCs beyond 1.5 years. A number of factors may have contributed, including lack of conditioning, in vitro cell manipulation including cytokine exposure, inability to transduce primitive hematopoietic stem cells, and paucity of long-term repopulating cells at the ages of the patients, suggesting earlier collection may be beneficial. This study is now closed to enrollment. Valuable information gained as a result of this study will contribute to future clinical gene therapy trials. Current work focuses on how to evaluate stem cell fitness prior to attempting gene therapy, minimizing manipulation required for gene correction and/or in vivo genetic correction and non-chemotherapy-based conditioning to facilitate engraftment. We would like to personally thank each patient and their families for participating in this study, as we could not have learned these lessons without their support. Disclosures Becker: GlycoMimetics: Research Funding; Abbvie: Research Funding; Amgen: Research Funding; BMS: Research Funding; CVS Caremark: Consultancy; Trovagene: Research Funding; Rocket Pharmaceuticals: Research Funding; Novartis: Research Funding; Pfizer: Consultancy; JW Pharmaceuticals: Research Funding. Adair:Miltenyi Biotec: Honoraria; RX Partners: Honoraria; Rocket Pharmaceuticals: Patents & Royalties: PCT/US2017/037967 and PCT/US2018/029983. Kiem:Rocket Pharmaceuticals: Consultancy; Homology Medicine: Consultancy; Magenta: Consultancy.

Alarms in the operating room remain a major source of annoyance and confusion. Nearly all alarms result from a transgression of certain alarm limits. We surveyed manufacturers at a major meeting of anesthesiologists for their default alarm limits. We also conducted a mail survey of anesthesiologists in the United States, Finland, and the Netherlands, to learn their chosen alarm limits, reasons for turning off the alarms, and estimates of the number of false alarms. The surveys of medical monitoring manufacturers demonstrated a wide variety of default alarm settings. Anesthesiologists' chosen alarm limits tended to parallel the manufacturers' defaults. Fewer than 30% of anesthesiologists stated that they did not turn off the alarms. The leading reason for turning off alarms was the large number of false alarms. Estimates of the number of false alarms varied from 30% to 76%. The desired role of alarms in anesthetic practice and some suggestions for the general improvement of alarms are discussed.

Background: Since the discovery of HIV, minimizing the use of donor blood has become increasingly important in surgical activity. In Finland, however, the use of homologous red blood has grown considerably during the past years. Therefore, we found it necessary to conduct a nationwide survey of transfusion practices in elective surgery. This report deals with transfusions in coronary artery bypass (CABG) operations in all Finnish cardiac centres. Methods: The study group comprised 804 primary CABG patients operated during a 2-year period. Two reviewers retrospectively examined the data concerning the use of and indications for homologous and autologous blood in the patient charts. Results: In all, 705 (88%) of patients received homologous blood. The proportions of patients receiving blood components differed between hospitals: from 53 to 99% for red cells, 2 to 22% for fresh frozen plasma and 5 to 49% for platelets. The variation was not caused by diverse patient populations: the mean number of blood component units transfused per patient differed from 1 to 6 between centres — even after adjustment for confounding variables. Multiple blood conservation methods were used in one centre. Nevertheless, homologous blood was administered to 88% of their patients. Conclusions: A considerable proportion of CABG patients are transfused with homologous blood in Finland compared to other countries. In addition, the transfusion practices proved highly variable between hospitals and were determined largely by local opinions. This study reveals a clear demand for prospective studies and constructive discussion among anaesthesiologists to establish uniform guidelines for blood use in cardiac surgery.

This study was performed to compare the efficacy of tropisetron, droperidol, and saline in the prevention of postoperative nausea and vomiting (PONV) and to compare the possible adverse effects of these drugs in gynecologic incontinence surgery.Using a randomized, double-blind study design, we studied 150 women undergoing gynecologic incontinence surgery with standardized general anesthesia. At the end of surgery, the patients received either tropisetron 5 mg, droperidol 1.25 mg, or 0.9% saline intravenously (IV). As a rescue antiemetic, the patients received metoclopramide 10 mg IV. The episodes of nausea, retching, and vomiting; the need for rescue treatment; and the type and severity of adverse events were recorded at four occasions during the 48-h observation period. Pain, anxiety, drowsiness, and general satisfaction were also evaluated on a linear numerical scale of 0-10. Complete response (no PONV within the 48-h observation period) occurred similarly in the study groups (tropisetron 25%, droperidol 22%, and placebo 18%). Tropisetron and droperidol had no effect on the incidence of nausea and retching. However, the incidence of vomiting was significantly less in the tropisetron group than in the placebo group (tropisetron 19%, droperidol 45%, and placebo 57%). The number of emetic episodes (retching and/or vomiting) per patient within 48 h was significantly decreased under tropisetron when compared with placebo (tropisetron 2.5 +/- 3.4, droperidol 4.2 +/- 6.1, placebo 5.9 +/- 7.1). With regard to adverse events, the patients in the droperidol group had significantly more anxiety than the placebo group (2-6 h postoperatively), more drowsiness than the tropisetron and placebo groups (0-2 h postoperatively), and more dissatisfaction than the tropisetron (0-6 h postoperatively) and placebo groups (2-6 h postoperatively). We conclude that tropisetron given 5 mg IV during anesthesia in gynecologic incontinence surgery effectively prevents vomiting but not nausea and retching, while 1.25 mg IV droperidol fails to prevent any of these emetic symptoms and results in adverse events. (Anesth Analg 1997;84:662-7)

Background: Epidural opioids have been recommended for analgesia after major surgery. In this report we describe how we introduced a low-cost, on-ward, nurse-based acute pain service using epidural fentanyl after major surgery in the University Hospitals of Oulu and Kuopio. Methods: In order to evaluate the feasibility of epidural fentanyl infusion administered by ward nurses, we prospectively assessed pain and side effects during fentanyl infusion (median duration 41 h) after major surgery in 305 consecutive patients in Kuopio. Results: 92% of the patients on the ward who had received epidural fentanyl infusion at 31–54 μg h-1 reported at most three episodes of severe pain (/ Numerical Rating Scale > 3/10) during the initial postoperative days, but there were some patients (8%) who reported several episodes (>3) of more severe pain (Numerical Rating Scale > 3). Three patients (0.9%) showed a diminished respiratory rate (

Two adult patients with upper airway obstruction due to epiglottitis and infectious mononucleosis requiring urgent airway management are presented. Successful establishment of an open airway was achieved by performing a minitracheotomy using the Seldinger technique followed finally with nasotracheal fibreoptic intubation.

The clinical and pharmacokinetic properties of ropivacaine and bupivacaine, both 5 mg/mL, used in axillary plexus block were compared in 60 patients in this randomized, double-blind, parallel-group study. The axillary plexus was identified with a nerve stimulator and 30, 35, or 40 mL of drug, depending on body weight, was injected into the perivascular sheath. In 20 patients, venous blood samples for the pharmacokinetic measurement were obtained over 24 h. The median onset times for anesthesia and complete motor block were in the range of 12-48 min and 5-20 min, respectively. Thirty-eight percent of patients in the ropivacaine group and 29% in the bupivacaine group needed additional nerve block(s) or supplementary analgesia and 7% in the bupivacaine group needed general anesthesia for surgery. Anesthesia was achieved in 52%-86% of the evaluated six nerves in the ropivacaine group and in 36%-87% in the bupivacaine group; the lowest figures were seen in the musculocutaneous nerve. In the pharmacokinetic study the mean peak plasma concentrations (Cmax) were 1.28 +/- 0.21 mg/L in the ropivacaine group and 1.28 +/- 0.47 mg/L in the bupivacaine group and the median times to peak plasma concentration (tmax) were 0.86 h and 0.96 h, respectively. The median terminal half-lives (t1/2) were 7.1 h and 11.5 h in the ropivacaine group and the bupivacaine group, respectively (P = 0.07). No statistically significant differences were found between ropivacaine and bupivacaine in either the clinical or the pharmacokinetic comparisons.

Magnesium may be beneficial in the control of ventricular ectopy and supraventricular tachyarrhythmias after coronary artery bypass graft (CABG) surgery, but it is not known whether a high-dose magnesium regimen is superior to a regimen keeping the patient normomagnesemic. A prospective randomized and double-blind clinical comparison was performed in 81 elective CABG patients in order to assess the effects of two different magnesium infusion regimens on electrolyte balance and postoperative arrhythmias. Forty-one patients (high-dose group, H) received 4.2 ± 0.7 g (mean ± SD), of magnesium sulfate before cardiopulmonary bypass, followed by an infusion of 11.9 ± 2.8 g of magnesium chloride until the first postoperative (PO) morning, and a further 5.5 ± 1.0 g until the second PO morning. Forty patients (low-dose group, L) received magnesium sulfate only after bypass to a total of 2.9 ± 0.5 g at the first, and 1.4 ± 0.1 g at the second PO morning. A blood cardioplegia technique was used in both groups, including bolus doses of magnesium chloride to a total of 2.4 ± 0.6 g and 2.3 ± 0.6 g to H and L patients, respectively. Continuous Holter tape-recording was used for 12 to 15 hours preoperatively, and for 48 hours postoperatively. Serum magnesium peaked in H patients on the first PO morning at 1.60 ± 0.25 mmol/L, whereafter it declined to the normal level on the third PO morning. Patients in the L group were normomagnesemic, except after the start of bypass. Recovery to spontaneous rhythm after declamping of the aorta was better in the H patients; only one patient had ventricular fibrillation (VF), whereas in the L group, four patients had VF and five patients needed a temporary pacemaker ( p = 0.016). Atrial fibrillation (AF) was detected in 3 H (7.3%), and 10 L patients (25%) within the first 48 PO hours ( p = 0.037). Ten H (24.3%) and 18 L patients (45.0%) had a total of 19 and 41 episodes of AF during the first PO week ( p p = 0.013).

Haemostasis was studied in patients receiving diclofenac for postoperative pain relief. Intravenous diclofenac 75 mg over 60 min, followed first by an infusion of 5 mg/h for 15 h and then by 50 mg every 8 h orally was administered to 20 patients undergoing total hip replacement. Eighteen patients receiving a placebo infusion and dextropropoxyfen per os served as controls. The results showed no statistically significant differences between the groups in blood loss, bleeding time (IVY), partial activated thromboplastin time and prothrombin complex assay or in platelet count. The measurements were performed preoperatively, 3 h postoperatively and on the fourth and tenth postoperative days. Plasma concentrations were also determined in ten patients undergoing knee arthroscopy. An i.v. diclofenac infusion of 75 mg over a period of 15 min was administered either once (to half of the patients) or twice. The mean diclofenac concentrations were 28 +/- 5 nmol/ml (+/- s.d.) after 15 min and 36 +/- 12 nmol/ml after the second infusion. The bleeding time in the arthroscopy patients receiving one or two bolus infusions of 75 mg diclofenac remained at the control level. It is concluded that diclofenac given as an intravenous infusion of 75 mg in 60 min, then 5 mg/h for 15 h, followed by 50 mg every 8 h orally, is a safe as dextropropoxyfen for pain relief in patients undergoing major orthopaedic surgery as far as coagulation data are concerned.

This study compared epidural and intravenous fentanyl infusions for pain relief for the first 20 h after thoracotomy, in order to examine whether an thoracic epidural fentanyl infusion offers clinical advantage over an intravenous infusion. Forty patients were assigned randomly to receive either fentanyl epidurally and saline intravenously or fentanyl intravenously and saline epidurally in a double-blind fashion. For each patient the fentanyl infusion was titrated to a rate required for pain relief (pain score less than 3, maximum 10). Patients reported similar median pain scores, but in the epidural group the required mean fentanyl infusion rate was less (0.95 +/- 0.23 vs. 1.67 +/- 0.46 micrograms.kg-1.h-1, P = 0.0001) and plasma fentanyl concentrations were less at 4 and 18 h (4 h: 0.81 +/- 0.27 vs. 1.38 +/- 0.36 ng.ml-1, P = 0.0001; 18 h: 0.94 +/- 0.32 vs. 1.54 +/- 0.65 ng.ml-1, P = 0.0007) than those in the intravenous group. Respiratory function was better preserved and the incidence of nausea and sedation was less in the epidural group than in the intravenous group. In conclusion there appears to be a clinical advantage to the epidural infusion over the intravenous infusion of fentanyl for analgesia after thoracotomy.