Serum proteomics reveals hemophagocytic lymphohistiocytosis-like phenotype in a subset of patients with multisystem inflammatory syndrome in children.

Children with Multisystem Inflammatory Syndrome in Children (MIS-C) can present with thrombocytopenia, which is a key feature of hemophagocytic lymphohistiocytosis (HLH). We hypothesized that thrombocytopenic MIS-C patients have more features of HLH. Clinical characteristics and routine laboratory parameters were collected from 228 MIS-C patients, of whom 85 (37%) were thrombocytopenic. Thrombocytopenic patients had increased ferritin levels; reduced leukocyte subsets; and elevated levels of ASAT and ALAT. Soluble IL-2RA was higher in thrombocytopenic children than in non-thrombocytopenic children. T-cell activation, TNF-alpha and IFN-gamma signaling markers were inversely correlated with thrombocyte levels, consistent with a more pronounced cytokine storm syndrome. Thrombocytopenia was not associated with severity of MIS-C and no pathogenic variants were identified in HLH-related genes. This suggests that thrombocytopenia in MIS-C is not a feature of a more severe disease phenotype, but the consequence of a distinct hyperinflammatory immunopathological process in a subset of children.

In Nordic countries 30-day mortality rate is half that estimated with EuroSCORE II in high-risk adult patients given aprotinin and undergoing mainly complex cardiac procedures.

Objectives. To describe current on- (isolated coronary arterty bypass grafting, iCABG) and off-label (non-iCABG) use of aprotinin and associated safety endpoints in adult patients undergoing high-risk cardiac surgery in Nordic countries. Design. Data come from 10 cardiac surgery centres in Finland, Norway and Sweden participating in the European Nordic aprotinin patient registry (NAPaR). Results. 486 patients were given aprotinin between 2016 and 2020. 59 patients (12.1%) underwent iCABG and 427 (87.9%) non-iCABG, including surgery for aortic dissection (16.7%) and endocarditis (36.0%). 89.9% were administered a full aprotinin dosage and 37.0% were re-sternotomies. Dual antiplatelet treatment affected 72.9% of iCABG and 7.0% of non-iCABG patients. 0.6% of patients had anaphylactic reactions associated with aprotinin. 6.4% (95 CI% 4.2%-8.6%) of patients were reoperated for bleeding. Rate of postoperative thromboembolic events, day 1 rise in creatinine >44µmol/L and new dialysis for any reason was 4.7% (95%CI 2.8%-6.6%), 16.7% (95%CI 13.4%-20.0%) and 14.0% (95%CI 10.9%-17.1%), respectively. In-hospital mortality and 30-day mortality was 4.9% (95%CI 2.8%-6.9%) and 6.3% (95%CI 3.7%-7.8%) in all patients versus mean EuroSCORE II 11.4% (95%CI 8.4%-14.0%, p < .01). 30-day mortality in patients undergoing surgery for aortic dissection and endocarditis was 6.2% (95%CI 0.9%-11.4%) and 6.3% (95%CI 2.7%-9.9%) versus mean EuroSCORE II 13.2% (95%CI 6.1%-21.0%, p = .11) and 14.5% (95%CI 12.1%-16.8%, p = .01), respectively. Conclusions. NAPaR data from Nordic countries suggest a favourable safety profile of aprotinin in adult cardiac surgery.

Use and safety of aprotinin in routine clinical practice: A European postauthorisation safety study conducted in patients undergoing cardiac surgery.

BACKGROUND: Aprotinin has been used to reduce blood loss and blood product transfusions in patients at high risk of major blood loss during cardiac surgery. Approval by the European Medicines Agency (EMA) for its current indication is limited to patients at high risk of major blood loss undergoing isolated coronary artery bypass graft surgery (iCABG). OBJECTIVE: To report current real-world data on the use and certain endpoints related to the safety of aprotinin in adult patients. DESIGN: The Nordic aprotinin patient registry (NAPaR) received data from 83 European centres in a noninterventional, postauthorisation safety study (PASS) performed at the request of the EMA. SETTING: Cardiac surgical centres committed to enrolling patients in the NAPaR. PATIENTS: Patients receiving aprotinin agreeing to participate. INTERVENTION: The decision to administer aprotinin was made by the treating physicians. MAIN OUTCOME MEASURES: Aprotinin safety endpoints were in-hospital death, thrombo-embolic events (TEEs), specifically stroke, renal impairment, re-exploration for bleeding/tamponade. RESULTS: From 2016 to 2020, 5309 patients (male 71.5%; >75 years 18.9%) were treated with aprotinin; 1363 (25.7%) underwent iCABG and 3946 (74.3%) another procedure, including a surgical treatment for aortic dissection ( n  = 660, 16.7%); 54.5% of patients received the full-dose regimen. In-hospital mortality in iCABG patients was 1.3% (95% CI, 0.66 to 1.84%) vs. 8.3% (7.21 to 8.91%) in non-iCABG patients; incidence of TEEs and postoperative rise in creatinine level greater than 44 µmol l -1 2.3% (1.48 to 3.07%) and 2.7% (1.79 to 3.49%) vs. 7.2% (6.20 to 7.79%) and 15.5% (13.84 to 16.06%); patients undergoing re-exploration for bleeding 1.4% (0.71 to 1.93%) vs. 3.0% (2.39 to 3.44%). Twelve cases of hypersensitivity/anaphylactic reaction (0.2%) were reported as Adverse Drug Reactions. CONCLUSION: The data in the NApaR indicated that in this patient population, at high risk of death or blood loss undergoing cardiac surgery, including complex cardiac surgeries other than iCABG, the incidence of adverse events is in line with data from current literature, where aprotinin was not used. TRIAL REGISTRATION: EU PAS register number: EUPAS11384.

Rotational thromboelastometry results are associated with care level in COVID-19.

High prevalence of thrombotic events in severely ill COVID-19 patients have been reported. Pulmonary embolism as well as microembolization of vital organs may in these individuals be direct causes of death. The identification of patients at high risk of developing thrombosis may lead to targeted, more effective prophylactic treatment. The primary aim of this study was to test whether rotational thromboelastometry (ROTEM) at admission indicates hypercoagulopathy and predicts the disease severity, assessed as care level, in COVID-19 patients. The study was designed as a prospective, observational study where COVID-19 patients over 18 years admitted to hospital were eligible for inclusion. Patients were divided into two groups depending on care level: (1) regular wards or (2) wards with specialized ventilation support. Conventional coagulation tests, blood type and ROTEM were taken at admission. 60 patients were included; age 61 (median), 67% men, many with comorbidities (e.g. hypertension, diabetes). The ROTEM variables Maximum Clot Firmness (EXTEM-/FIBTEM-MCF) were higher in COVID-19 patients compared with in healthy controls (p < 0.001) and higher in severely ill patients compared with in patients at regular wards (p < 0.05). Our results suggest that hypercoagulopathy is present early in patients with mild to moderate disease, and more pronounced in severe COVID-19 pneumonia. Non-O blood types were not overrepresented in COVID-19 positive patients. ROTEM variables showed hypercoagulopathy at admission and this pattern was more pronounced in patients with increased disease severity. If this feature is to be used to predict the risk of thromboembolic complications further studies are warranted.

Silicone Oil Decreases Biofilm Formation in a Capacitance-Based Automatic Urine Measurement System.

Capacitance-based automatic urine measurement is a validated technique already implemented in clinical practice. However, albuminuria and free hemoglobinuria cause progressive biofilm buildup on the capacitance sensors of the urinometers. The aim of this experimental study is to investigate the influence of albumin and free hemoglobin on the capacitance signal of an automatic urinometer with and without the addition of silicone oil. A solution of Ringer's acetate mixed with either albumin or free hemoglobin was run through an automatic urinometer containing either a water-soluble capsule with silicone oil or not. In total, around 500 capacitance measurements were retrieved from the albumin and free hemoglobin group, respectively. The mean increase in capacitance in the albumin 3 g/L group was 257 ± 100 pF without and 105 ± 30 pF with silicone oil, respectively, during 24 h. After ten hours of recording, differences between the two albumin groups reached statistical significance. For the free hemoglobin groups (0.01 g/L), the mean increase in capacitance was 190 ± 170 pF with silicone oil, and 324 ± 80 pF without, with a significant difference between the groups after 20 h and onwards. Coating of the capacitance measurement membrane of the automatic urinometer by albumin or free hemoglobin was significantly decreased by silicone oil, prolonging the functionality of the device.

Platelet function analysed by ROTEM platelet in cardiac surgery after cardiopulmonary bypass and platelet transfusion.

OBJECTIVES: The aim of this study was to investigate whether ROTEM platelet can provide additional information to the traditional ROTEM analysis to guide treatment with platelet transfusions in cardiac surgery and to identify factors triggering platelet administration. BACKGROUND: Platelets play a crucial role in coagulation and haemostasis after cardiac surgery. Excessive bleeding after cardiopulmonary bypass usually requires transfusions of blood products, including platelets. The ROTEM platelet is a novel point-of-care analysis for whole blood. MATERIALS AND METHODS: We included 23 patients scheduled for complex cardiac surgery. ROTEM (in-tem, ex-tem), ROTEM platelet (ARA-tem, ADP-tem and TRAP-tem) and platelet count were analysed before induction of anaesthesia (T0), after cardiopulmonary bypass and protamine reversal (T1) and after platelet transfusion (T2, n = 10). RESULTS: ROTEM and ROTEM platelet tests were all significantly reduced between T0 and T1. ROTEM parameters improved significantly after platelet transfusion. Regarding ROTEM platelet, only TRAP-tem increased between T1 and T2 (P = .008). Factors triggering platelet transfusion were long duration of surgery and time on cardiopulmonary bypass. CONCLUSION: ROTEM platelet with thrombin activation, TRAP-tem, improved significantly, indicating that platelet transfusion may reverse cardiopulmonary bypass-induced platelet dysfunction. Further studies are needed to evaluate whether TRAP-tem can be a valuable analysis regarding indications for transfusion of platelets after extensive cardiac surgery.

Cardiac Arrest Prior to Venoarterial Extracorporeal Membrane Oxygenation: Risk Factors for Mortality.

OBJECTIVES: Mortality after cardiac arrest remains high despite initiation of venoarterial extracorporeal membrane oxygenation. We aimed to identify pre-venoarterial extracorporeal membrane oxygenation risk factors of 90-day mortality in patients with witnessed cardiac arrest and with greater than or equal to 1 minute of cardiopulmonary resuscitation before venoarterial extracorporeal membrane oxygenation. The association between preimplant variables and all-cause mortality at 90 days was analyzed with multivariable logistic regression. DESIGN: Retrospective observational cohort study. SETTING: Tertiary medical center. PATIENTS: Seventy-two consecutive patients with cardiac arrest prior to venoarterial extracorporeal membrane oxygenation cannulation. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Median age was 56 years (interquartile range, 43-56 yr), 75% (n = 54) were men. Out-of-hospital cardiac arrest occurred in 12% (n = 9) of the patients. Initial cardiac rhythm was nonshockable in 57% (n = 41) and shockable in 43% (n = 31) of patients. Median cardiopulmonary resuscitation duration was 21 minutes (interquartile range, 10-73 min; range, 1-197 min]. No return of spontaneous circulation was present in 64% (n = 46) and postarrest cardiogenic shock in 36% (n = 26) of the patients at venoarterial extracorporeal membrane oxygenation cannulation. Median duration of venoarterial extracorporeal membrane oxygenation was 5 days (interquartile range, 2-12 d). The 90-day overall mortality and in-hospital mortality were 57% (n = 41), 53% (n = 38) died during venoarterial extracorporeal membrane oxygenation, and 43% (n = 31) were successfully weaned. All survivors had Cerebral Performance Category score 1-2 at discharge to home. Multivariable logistic regression analysis identified initial nonshockable cardiac arrest rhythm (odds ratio, 12.2; 95% CI, 2.83-52.7; p = 0.001), arterial lactate (odds ratio per unit, 1.15; 95% CI, 1.01-1.31; p = 0.041), and ischemic heart disease (7.39; 95% CI, 1.57-34.7; p = 0.011) as independent risk factors of 90-day mortality, whereas low-flow duration, return of spontaneous circulation, and age were not. CONCLUSIONS: In 72 patients with cardiac arrest before venoarterial extracorporeal membrane oxygenation initiation, nonshockable rhythm, arterial lactate, and ischemic heart disease were identified as independent pre-venoarterial extracorporeal membrane oxygenation risk factors of 90-day mortality. The novelty of this study is that the metabolic state, expressed as level of lactate just before venoarterial extracorporeal membrane oxygenation initiation seems more predictive of outcome than cardiopulmonary resuscitation duration or absence of return of spontaneous circulation.

A Pilot Evaluation of a Capacitance-Based Automatic Urinometer in a Pediatric Intensive Care Setting.

OBJECTIVES: To compare a modified capacitance-based automatic urinometer to a manual urinometer, with regard to precision of measurement and to evaluate the staff's opinion regarding the automatic urinometer. DESIGN: Prospective observational cohort study. SETTING: PICU at Astrid Lindgren's Children Hospital in Solna, Sweden. PATIENTS: Twelve children weighing up to 10 kg with an indwelling urinary catheter in place before enrollment. INTERVENTIONS: Measurement of hourly diuresis using either an automatic urinometer or manual urinometer. MEASUREMENTS AND MAIN RESULTS: Hourly diuresis was measured with an automatic urinometer (n = 127; Sippi; Observe Medical Nordic AB, Gothenburg, Sweden) or an manual urinometer (n = 83; Unometer Safeti Plus; Convatec, Lejre, Denmark) and thereafter validated with a measuring cylinder. The absolute mean bias was -1.1 mL for the automatic urinometer (CI, -0.6 to -1.5) and -0.6 mL (CI, ± 0.0 to -1.2) for the manual urinometer (p = 0.21). The SDs were 2.6 and 2.8 mL, respectively. User evaluation comparing the automatic urinometer with the manual urinometer concerning the ease of use was made with a questionnaire (n = 18). The majority of staff preferred the automatic urinometer to the manual urinometer in terms of ease of use, learning, and handling. CONCLUSIONS: The two urinometers were comparable in performance for children weighing up to 10 kg. Taking into account the overwhelming staff satisfaction with the automatic urinometer and benefits in less well-staffed wards as well as lack of temporal deviation, the modified automatic urinometer may be considered for clinical use in the PICU.

VA-ECMO Support in Nonsurgical Patients With Refractory Cardiogenic Shock: Pre-Implant Outcome Predictors.

Refractory cardiogenic shock (RCS) is associated with a high mortality. Veno-arterial extracorporeal membrane oxygenation (VA-ECMO) is increasingly used as acute cardiopulmonary support but selection of VA-ECMO candidates remains challenging. There are limited data on which pre-VA-ECMO variables that predict outcome. The aim of this study was to identify pre-VA-ECMO predictors of 90-day mortality. We retrospectively analyzed 76 consecutive patients (median age 52; interquartile range [IQR]: 37-60) supported with VA-ECMO due to RCS. The association between pre-implant variables and all-cause mortality at 90 days was analyzed with multivariable logistic regression. Main etiologies of RCS were acute myocardial infarction 51% and other AHF etiologies 49%. Cardiopulmonary resuscitation was performed in 54% of patients before initiation of VA-ECMO. Median duration of VA-ECMO was 5 days (IQR: 2-11). The 90-day overall mortality was 49% and in-hospital mortality was 50%; 46% died on VA-ECMO, 37% were successfully weaned, 13% were bridged to heart transplantation, and 4% to left ventricular assist device. Multivariable logistic regression analysis identified arterial lactate (odds ratio [OR] per mmol/L: 1.15; 95% confidence interval [CI]: 1.06-1.24; P = 0.001) and number of inotropes and vasopressors (OR per agent: 2.14; 95% CI: 1.26-3.63; P = 0.005) as independent predictors of 90-day mortality. In RCS patients arterial lactate level and number of inotropes and vasopressors were identified as independent pre-VA-ECMO predictors of 90-day mortality. Thus, the severity of cardiogenic shock expressed as levels of lactate and vasoactive agents just before start of VA-ECMO may be more predictive of outcome than the specific etiology of cardiogenic shock.

Calculation Algorithm Reduces Protamine Doses Without Increasing Blood Loss or the Transfusion Rate in Cardiac Surgery: Results of a Randomized Controlled Trial.

OBJECTIVES: The aim of the study was to investigate whether the HeProCalc algorithm affects heparin and protamine dosage, postoperative blood loss, and transfusion rate. DESIGN: Randomized controlled trial. SETTING: University hospital. PARTICIPANTS: The study comprised 210 cardiac surgery patients undergoing cardiac surgery with cardiopulmonary bypass. Twenty patients were excluded because of re-exploration for localized surgical bleeding (n = 9), violation of protocol (n = 2), aprotinin use (n = 3 and nadir body temperature <32°C (n = 6). INTERVENTIONS: Study participants were randomly assigned to either traditional heparin and protamine dosage based on body weight only (control group) or dosage based on the HeProCalc algorithm (intervention group). MEASUREMENTS AND MAIN RESULTS: The initial median heparin dose was 32,500 IU (interquartile range [IQR] 30,000-35,000) in the intervention group compared with 35,000 IU (IQR 30,000-37,500) (p = 0.025) in the control group. The total heparin dose in the intervention group was 40,000 IU (IQR 32,500-47,500) compared with 42,500 IU (IQR 35,000-50,000) in the control group (p = 0.685). The total protamine dose was 210 mg (IQR 190-240) in the intervention group compared with 350 mg (IQR 300-380) (p < 0.001) in the control group. The ratio of total protamine to initial dose of heparin in the intervention group was 0.62 compared with 1.0 (p < 0.001). The amount of chest tube bleeding after 12 postoperative hours was 320 mL (IQR 250-460) in the intervention group compared with 350 mL (IQR 250-450) (p = 0.754) in the control group. Neither the transfusion rate nor postoperative blood loss differed significantly between the 2 groups. CONCLUSION: Use of the HeProCalc algorithm reduced protamine dosage and the protamine/heparin ratio after cardiopulmonary bypass compared with conventional dosage based on weight without significant effect on postoperative blood loss or the transfusion rate.

Adjunctive interferon-γ immunotherapy in a pediatric case of Aspergillus terreus infection.

Aspergillus terreus causes invasive aspergillosis (IA) in immunocompromised patients. Treatment is complicated by intrinsic resistance to amphotericin B and thereby contributing to a high mortality. Therefore, we conducted in vitro studies to investigate the effectivity of adjunctive recombinant interferon-γ immunotherapy. We describe a pediatric patient with A. terreus IA who received adjunctive recombinant interferon-γ (rIFNγ) immunotherapy. In vitro studies were conducted to investigate the capacity of rIFNγ to improve antifungal host defense in terms of fungal killing ability and the release of pro-inflammatory cytokines in cells of the patient as well as healthy controls. An 8-year-old female pediatric patient with leukemia developed A. terreus IA. She clinically deteriorated and had high serum galactomannan levels despite broad antifungal therapy. Therefore, adjunctive immune stimulatory therapy with rIFNγ was initiated. After 3 weeks of treatment, galactomannan levels decreased and the patient clinically showed improvement. Addition of rIFNγ boosted the capacity of monocytes of healthy volunteers to mount TNFα and IL-1ß cytokine responses to Escherichia coli LPS, and increased TNFα response to both A. terreus and Aspergillus fumigatus. Monocytes isolated from the patient's blood demonstrated a similar augmented cytokine induction in response to rIFNγ. In addition, rIFNγ increased the capacity of monocytes from healthy volunteers as well as monocytes from the patient to kill A. terreus spores. Adjuvant immunotherapy with rIFNγ might be a promising additional treatment strategy that could be used to improve outcome in patients with refractory invasive A. terreus infections or other resistant invasive Aspergillus infections.

Laparotomy causes loss of peritoneal mesothelium prevented by humidified CO2 insufflation in rats.

INTRODUCTION: Avoiding tissue desiccation is a common recommendation to reduce postoperative complications following open abdominal surgery, although difficult to achieve delicately without damaging the peritoneal mesothelium. Insufflation of humidified-warm CO2 into the abdomen during open abdominal surgery is proposed as an invisible, effortless way to prevent desiccation. We hypothesized that desiccation during open abdominal surgery would cause loss of peritoneal mesothelium that would be prevented by insufflation of humidified-warm CO2. METHODS: Nine Wistar rats were assigned to 1 h of anesthesia only, laparotomy only, or laparotomy with insufflation of humidified-warm CO2. Twelve hours after treatment, rats were euthanized and tissue samples were excised. Scanning electron microscopy (SEM) and light microscopy (LM) images of visceral and parietal peritoneum were scored by two independent, blinded examiners for loss of mesothelium and other indications of inflammation, including measurement of apoptosis by detection of DNA cleavage. RESULTS: Loss of peritoneal mesothelium was found in peritoneum exposed to laparotomy only (SEM: P = 0.002; LM: P = 0.01), and mesothelial loss was reduced by humidified-warm CO2 (SEM: P < 0.001; LM P = 0.004). Similarly, DNA cleavage was significantly higher on the peritoneal surface following laparotomy only, compared with anesthesia only (P = 0.0055) and laparotomy with humidified-warm CO2 insufflation (P = 0.0003). CONCLUSIONS: In a rat model, exposing the peritoneal mesothelial to conditions that replicate minimum recommended air flow within an operating room causes inadvertent loss of mesothelium and signs of inflammation that can be prevented by insufflating humidified-warm CO2 into the open abdominal cavity.

Ticagrelor pharmacokinetics and pharmacodynamics in patients with NSTEMI after a 180-mg loading dose.

The pharmacokinetics after a 180-mg loading dose (LD) of ticagrelor has not been thoroughly investigated in NSTEMI patients. We aimed to compare the ticagrelor uptake and on-treatment platelet reactivity between non-ST-segment elevation myocardial infarction (NSTEMI) patients and a control group of patients with stable coronary artery disease (SCAD) undergoing elective percutaneous coronary intervention. We performed an observational, prospective, single-center study including 40 NSTEMI patients and 20 SCAD controls. Key exclusion criteria included ongoing opioid treatment. Both groups received a 180-mg ticagrelor LD, and blood samples were taken pre-dose and 1, 2, 3, 4, 5, and 6 hours post-LD. Plasma concentrations of ticagrelor and its active metabolite AR-C124910XX were determined by validated methods. Platelet aggregation was tested using ADP-induced multiple electrode aggregometry. The primary endpoint was the time to maximal ticagrelor concentration (Tmax). Clinical trial registration identifier number: NCT02292277. None of the pharmacokinetic variables differed significantly between the groups, including the Tmax of ticagrelor (2.0h [1.0-3.0] versus 2.0h [2.0-3.0], p = 0.393) and the active metabolite AR-C124910XX (3.0 [2.0-4.0] versus 3.0 [2.5-4.0], p = 0.289). High on-treatment platelet reactivity (HPR) was defined as > 46 aggregation units and was at one hour seen in 15% of the NSTEMI patients versus 10% of the controls (p = 1.0). At two hours post the 180-mg ticagrelor LD, 3% of the NSTEMI patients had HPR compared with none of the controls (p = 1.0). In conclusion, the uptake of ticagrelor was not significantly slower in NSTEMI patients not receiving opioids compared with the SCAD controls, leading to adequate onset of platelet inhibition in both groups.

Mobile ultra-clean unidirectional airflow screen reduces air contamination in a simulated setting for intra-vitreal injection.

The aim of this study is to determine whether the use of a mobile ultra-clean laminar airflow screen reduces the air-borne particle counts in the setting of a simulated procedure of an intra-vitreal injection. A mobile ultra-clean unidirectional airflow (UDF) screen was tested in a simulated procedure for intra-vitreal injections in a treatment room without mechanical ventilation. One UDF was passed over the instrument tray and the surgical area. The concentration of particles was measured in the background, over the instrument table, and next to the ocular area. The degree of protection was calculated at the instrument table and at the surgical site. Use of the UDF mobile screen reduced the mean particle concentration (particles > 0.3 microns) on the instrument table by a factor of at least 100.000 (p < 0.05), and over the patient's eye by at least a factor of 436 (p < 0.05), which in clinical practice translates into significantly reduced air contamination. Mobile UDF screen reduces the mean particle concentration substantially. The mobile UDF screen may therefore allow for a safer procedural environment for ambulatory care procedures such as intra-vitreal injections in treatment rooms.

In Vitro Effects of Pantoprazole on Platelet Aggregation in Blood Samples From Clopidogrel and Aspirin-treated Patients.

Platelet inhibition during treatment with the antiplatelet drug clopidogrel is prone to great interindividual variability and is believed to be affected by several factors such as genetics and drug-drug interactions. Proton pump inhibitors have been shown to interfere with the liver metabolism of clopidogrel. However, there are limited data on any direct effects proton pump inhibitors may have on clopidogrel. The aim of the study was to evaluate whether the in vitro addition of pantoprazole affects platelet aggregation in blood samples from clopidogrel and aspirin-treated patients. Blood samples were drawn from 66 patients on clopidogrel and aspirin who underwent coronary angiography. Platelet aggregation was analyzed using the bed-side Plateletworks assay before and after the addition of 2 different amounts of pantoprazole. The addition of 2.5 µL (4 mg/mL) pantoprazole, final concentration 0.01 mg/mL, was followed by a significant reduction (26%, P ≤ 0.001) of platelet aggregation, which was further reduced (39%, P ≤ 0.001) when a higher dose, 10 µL (4 mg/mL), final concentration 0.04 mg/mL, was added. In conclusion, platelet aggregation was significantly decreased by in vitro addition of pantoprazole. To explore the clinical relevance of this, future studies are needed.

An Adjusted Calculation Model Allows for Reduced Protamine Doses without Increasing Blood Loss in Cardiac Surgery.

Background Heparin dosage for anticoagulation during cardiopulmonary bypass (CPB) is commonly calculated based on the patient's body weight. The protamine-heparin ratio used for heparin reversal varies widely among institutions (0.7-1.3 mg protamine/100 IU heparin). Excess protamine may impair coagulation. With an empirically developed algorithm, the HeProCalc program, heparin, and protamine doses are calculated during the procedure. The primary aim was to investigate whether HeProCalc-based dosage of heparin could reduce protamine use compared with traditional dosages. The secondary aim was to investigate whether HeProCalc-based dosage of protamine affected postoperative bleeding. Patients and Methods We consecutively randomized 40 patients into two groups. In the control group, traditional heparin and protamine doses, based on body weight alone, were given. In the treatment group, the HeProCalc program was used, which calculated the initial heparin bolus dose from weight, height, and baseline activated clotting time and the protamine dose at termination of CPB. Results We analyzed the results from 37 patients, after exclusion of three patients. Equal doses of heparin were given in both groups, whereas significantly lower mean doses of protamine were given in the treatment group versus control group (211 ± 56 vs. 330 ± 61 mg, p < 0.001). Postoperative bleeding was less in the HeProCalc group (280 ± 229 mL) as compared with the control group (649 ± 279 mL). However, this difference was not found statistically significant (p = 0.074). Conclusion HeProCalc-based dosage of heparin and protamine allowed for reduced protamine use after CPB compared with when conventional calculations were used. Furthermore, HeProCalc-based regimen for heparin reversal suggested less postoperative bleeding, although the difference between the groups was not statistically significant.

Performance and user evaluation of a novel capacitance-based automatic urinometer compared with a manual standard urinometer after elective cardiac surgery.

INTRODUCTION: In the intensive care setting, most physiologic parameters are monitored automatically. However, urine output (UO) is still monitored hourly by manually handled urinometers. In this study, we evaluated an automatic urinometer (AU) and compared it with a manual urinometer (MU). METHODS: This prospective study was carried out in the intensive care unit of a cardiothoracic surgical clinic. In postoperative patients (n = 34) with indwelling urinary catheters and an expected stay of 24 hours or more, hourly UO samples were measured with an AU (Sippi, n = 220; Observe Medical, Gothenburg, Sweden) or an MU (UnoMeter™ 500, n = 188; Unomedical, Birkerød, Denmark) and thereafter validated by cylinder measurements. Malposition of the instrument at the time of reading excluded measurement. Data were analyzed with the Bland-Altman method. The performance of the MU was used as the minimum criterion of acceptance when the AU was evaluated. The loss of precision with the MU due to temporal deviation from fixed hourly measurements was recorded (n = 108). A questionnaire filled out by the ward staff (n = 28) was used to evaluate the ease of use of the AU compared with the MU. RESULTS: Bland-Altman analysis showed a smaller mean bias for the AU (+1.9 ml) compared with the MU (+5.3 ml) (P <0.0001). There was no statistical difference in measurement precision between the two urinometers, as defined by their limits of agreement (±15.2 ml vs. ±16.6 ml, P = 0.11). The mean temporal variation with the MU was ±7.4 minutes (±12.4%), and the limits of agreement were ±23.9 minutes (±39.8%), compared with no temporal variation with the AU (P <0.0001). The ward staff considered the AU easy to learn to use and rated it higher than the MU (P <0.0001). CONCLUSIONS: The AU was not inferior to the MU and was significantly better in terms of bias, temporal deviation and staff opinion, although the clinical relevance of these findings may be open to discussion.

Adenosine diphosphate-induced single-platelet count aggregation and bleeding in clopidogrel-treated patients undergoing coronary artery bypass grafting.

OBJECTIVES: To investigate the association between adenosine diphosphate (ADP)-induced platelet aggregation measured by single-platelet count testing and postoperative blood loss in clopidogrel-treated patients with acute coronary syndromes undergoing coronary artery bypass grafting (CABG). DESIGN: Prospective observational study. SETTING: Clinical study in one cardiac surgery center. PARTICIPANTS: Eighty-eight patients treated with clopidogrel (300-600 mg loading dose followed by 75 mg daily) within 7 days before CABG. INTERVENTIONS: Platelet function was assessed preoperatively by single-platelet count ADP-induced platelet aggregation. Postoperative blood loss and transfusion requirements were recorded. MEASUREMENTS AND MAIN RESULTS: There was no significant association between ADP-induced platelet aggregation and blood loss 12 hours postoperatively (estimate -7.51; 95% confidence interval [CI]: -16.9-1.9; p = 0.12). ADP-induced platelet aggregation was associated significantly with the number of platelet concentrates administered within 24 hours after surgery (incidence rate ratio [IRR] 0.95; 95% CI: 0.92-0.98; p<0.01), but not to the number of packed red blood cells (IRR 0.98; 95% CI: 0.95-1.01; p = 0.14). CONCLUSIONS: Preoperative ADP-induced platelet aggregation measured by single-platelet count testing in clopidogrel-treated patients with acute coronary syndromes undergoing CABG was not associated with postoperative blood loss or packed red blood cells transfused, but was associated significantly with number of platelet concentrates administered during the initial 24 postoperative hours.