Analysis of exhaled breath to identify critically ill patients with ventilator-associated pneumonia.

Ventilator-associated pneumonia commonly occurs in critically ill patients. Clinical suspicion results in overuse of antibiotics, which in turn promotes antimicrobial resistance. Detection of volatile organic compounds in the exhaled breath of critically ill patients might allow earlier detection of pneumonia and avoid unnecessary antibiotic prescription. We report a proof of concept study for non-invasive diagnosis of ventilator-associated pneumonia in intensive care (the BRAVo study). Mechanically ventilated critically ill patients commenced on antibiotics for clinical suspicion of ventilator-associated pneumonia were recruited within the first 24 h of treatment. Paired exhaled breath and respiratory tract samples were collected. Exhaled breath was captured on sorbent tubes and then analysed using thermal desorption gas chromatography-mass spectrometry to detect volatile organic compounds. Microbiological culture of a pathogenic bacteria in respiratory tract samples provided confirmation of ventilator-associated pneumonia. Univariable and multivariable analyses of volatile organic compounds were performed to identify potential biomarkers for a 'rule-out' test. Ninety-six participants were enrolled in the trial, with exhaled breath available from 92. Of all compounds tested, the four highest performing candidate biomarkers were benzene, cyclohexanone, pentanol and undecanal with area under the receiver operating characteristic curve ranging from 0.67 to 0.77 and negative predictive values from 85% to 88%. Identified volatile organic compounds in the exhaled breath of mechanically ventilated critically ill patients show promise as a useful non-invasive 'rule-out' test for ventilator-associated pneumonia.

A Retrospective Observational Study of Anticoagulation Practices in Critically ill Patients with Atrial Fibrillation Admitted to the Intensive Care Unit.

BACKGROUND: Atrial Fibrillation (AF) is the most common arrhythmia in critically ill patients. AF precipitates thromboembolic (TE) events. International guidelines recommend long-term anticoagulation for AF patients dependent upon the risk of TE versus major bleeding events. The CHA2DS2VASc and HAS-BLED scores are used to calculate these risks, but have not been validated in intensive care. Little is known about the risk/benefit ratio of prescribing anticoagulation to patients with AF in the intensive care setting. METHODS: This observational study included patients who were admitted to intensive care and had AF episodes during admission. We aimed to 1) describe the anticoagulation strategies used in critically ill patients with AF, 2) determine the percentage of patients who received guideline-compliant anticoagulation and 3) compare anticoagulation strategies in patients with new onset AF (NOAF) and known AF. Demographic data was extracted from electronic health records. Therapeutic anticoagulation prescribed during AF episodes and outcomes were collected. CHA2DS2VASc and HAS-BLED scores were calculated and correlated with TE and bleeding events. RESULTS: The incidence of AF in our cohort was 13.8%. Anticoagulation was administered in 34.0% of patients. Anticoagulation use did not affect morbidity or mortality outcomes. Patients with pre-existing AF were anticoagulated more often compared to patients with NOAF. CHA2DS2VASc scores and TE events, and HAS-BLED scores and bleeding events did not correlate well. CONCLUSION: AF is common in critical care. Current guidelines on anticoagulation in AF may not be directly transferable to the critical care setting.

Retraction notice to "Does the type of volume therapy influence endothelial-related coagulation in the critically ill?" [Br J Anaesth 75 (1995) 740-6].

This article has been retracted: please see Elsevier Policy on Article Withdrawal (https://www.elsevier.com/about/our-business/policies/article-withdrawal). This article has been retracted at the request of the Editor-in-Chief, Professor Hugh Hemmings, based on the recommendations of Justus-Liebig-University Giessen following an internal review of research conducted by Joachim Boldt at the University. This is further described in 'Further Retractions of Articles by Joachim Boldt', https://doi.org/10.1016/j.bja.2020.02.024.

Performance of influenza-specific triage tools in an H1N1-positive cohort: P/F ratio better predicts the need for mechanical ventilation and critical care admission.

BACKGROUND: Pandemic influenza presents a major threat to global health and socioeconomic well-being. Future demand for critical care may outstrip supply and force clinicians to triage patients for admission. We evaluated the Simple Triage Scoring System (STSS), Ontario Health Plan for an Influenza Epidemic (OHPIP) and PaO2 /FiO2  (P/F) ratio to determine utility in predicting need for mechanical ventilation. METHODS: We conducted a retrospective case note review of patients admitted to two centres, Royal Liverpool University Hospital and Countess of Chester Hospital, during the UK influenza pandemic of 2010-11. Demand for critical care during this period forced hospitals in Cheshire and Merseyside to implement escalation policies and increase capacity. Inclusion criteria were polymerase chain reaction-confirmed H1N1 influenza and age >18 years. Exclusion criteria were no evidence of treatment for influenza, patient not admitted to hospital or the inability to locate case notes. RESULTS: One hundred and one patients were included, 29 were admitted to critical care and 23 required mechanical ventilation. The P/F ratio predicted the need for mechanical ventilation with a receiver operating characteristic area under the curve (ROC AUC) of 0.885 (CI 0.817-0.952). Predictive ability was not reduced when the P/F ratio had to be estimated using the Pandharipande tool. The STSS score predicted the need for mechanical ventilation [ROC AUC 0.798 (CI 0.704-0.891)]. The reverse triage component of the OHPIP tool was a poor predictor of patient outcome. CONCLUSIONS: The P/F ratio was a better predictor of need for mechanical ventilation than STSS. The P/F ratio is a simple and accepted determinant of hypoxaemia and should be used if secondary triaging becomes necessary during future influenza pandemics.

Pyruvate: immunonutritional effects on neutrophil intracellular amino or alpha-keto acid profiles and reactive oxygen species production.

For the first time the immunonutritional role of pyruvate on neutrophils (PMN), free α-keto and amino acid profiles, important reactive oxygen species (ROS) produced [superoxide anion (O(2) (-)), hydrogen peroxide (H(2)O(2))] as well as released myeloperoxidase (MPO) acitivity has been investigated. Exogenous pyruvate significantly increased PMN pyruvate, α-ketoglutarate, asparagine, glutamine, aspartate, glutamate, arginine, citrulline, alanine, glycine and serine in a dose as well as duration of exposure dependent manner. Moreover, increases in O(2) (-) formation, H(2)O(2)-generation and MPO acitivity in parallel with intracellular pyruvate changes have also been detected. Regarding the interesting findings presented here we believe, that pyruvate fulfils considerably the criteria for a potent immunonutritional molecule in the regulation of the PMN dynamic α-keto and amino acid pools. Moreover it also plays an important role in parallel modulation of the granulocyte-dependent innate immune regulation. Although further research is necessary to clarify pyruvate's sole therapeutical role in critically ill patients' immunonutrition, the first scientific successes seem to be very promising.

Continuous S-(+)-ketamine administration during elective coronary artery bypass graft surgery attenuates pro-inflammatory cytokine response during and after cardiopulmonary bypass.

BACKGROUND: Coronary artery bypass surgery (CABG) with cardiopulmonary bypass (CPB) leads to elevated circulating plasma cytokines. In this prospective randomized study, the effect of an S-(+)-ketamine-based anaesthetic protocol on perioperative plasma cytokine levels was compared with standard anaesthesia with propofol and sufentanil during CPB. METHODS: Patients undergoing elective on-pump CABG were randomly allocated to anaesthesia with sufentanil-propofol-midazolam (Sufentanil) or S-(+)-ketamine-propofol-midazolam (Ketamine). Blood samples were obtained before induction of anaesthesia (baseline) and also at 1, 6, and 24 h after aortic unclamping. Plasma levels of the interleukins (IL)-6, IL-8, IL-10, and tumour necrosis factor (TNF)-alpha were determined by enzyme-linked immunosorbent assay. RESULTS: One hundred and twenty-eight patients were studied (Ketamine: n=60; Sufentanil: n=68). All measured cytokines increased during and after CPB. However, the increase in the pro-inflammatory cytokines IL-6 and IL-8 6 h after aortic unclamping was significantly lower in the Ketamine group compared with the Sufentanil group [mean (sd): IL-6 56.75 (46.28) pg ml⁻¹ (Ketamine) vs 172.64 (149.93) pg ml⁻¹ (Sufentanil), P<0.01; IL-8 7.74 (14.72) pg ml⁻¹ (Ketamine) vs 26.3 (47.12) pg ml⁻¹ (Sufentanil), P<0.01]. In contrast, the anti-inflammatory cytokine IL-10 showed higher levels 1 h after unclamping in the Ketamine group compared with the Sufentanil group [mean (sd): 69.59 (78.78) vs 24.63 (37.7) pg ml⁻¹, P<0.001]. CONCLUSION: Our data demonstrate that S-(+)-ketamine possesses anti-inflammatory potential. Anaesthesia with S-(+)-ketamine may have beneficial effects in attenuating the CPB-induced systemic inflammatory response.

Effects of alpha-ketoglutarate on neutrophil intracellular amino and alpha-keto acid profiles and ROS production.

The aim of this study was to determine the effects of alpha-ketoglutarate on neutrophil (PMN), free alpha-keto and amino-acid profiles as well as important reactive oxygen species (ROS) produced [superoxide anion (O(2) (-)), hydrogen peroxide (H(2)O(2))] and released myeloperoxidase (MPO) activity. Exogenous alpha-ketoglutarate significantly increased PMN alpha-ketoglutarate, pyruvate, asparagine, glutamine, asparatate, glutamate, arginine, citrulline, alanine, glycine and serine in a dose as well as duration of exposure dependent manner. Additionally, in parallel with intracellular alpha-ketoglutarate changes, increases in O(2) (-) formation, H(2)O(2)-generation and MPO activity have also been observed. We therefore believe that alpha-ketoglutarate is important for affecting PMN "susceptible free amino- and alpha-keto acid pools" although important mechanisms and backgrounds are not yet completely explored. Moreover, our results also show very clearly that changes in intragranulocytic alpha-ketoglutarate levels are relevant metabolic determinants in PMN nutrition considerably influencing and modulating the magnitude and quality of the granulocytic host defense capability as well as production of ROS.

The whole blood phagocytosis assay: a clinically relevant test of neutrophil function and dysfunction in community-acquired pneumonia.

OBJECTIVE: To refine and validate a neutrophil function assay with clinical relevance for patients with community-acquired pneumonia (CAP). DESIGN: Two phase cross-sectional study to standardise and refine the assay in blood from healthy volunteers and test neutrophil phagocytic function in hospital patients with CAP. PARTICIPANTS: Phase one: Healthy adult volunteers (n = 30). Phase two: Critical care patients with severe CAP (n = 16), ward-level patients with moderate CAP (n = 15) and respiratory outpatients (no acute disease, n = 15). RESULTS: Our full standard operating procedure for the assay is provided. Patients with severe CAP had significantly decreased neutrophil function compared to moderate severity disease (median phagocytic index 2.8 vs. 18.0, p = 0.014). Moderate severity pneumonia neutrophil function was significantly higher than control samples (median 18.0 vs. 1.6, p = 0.015). There was no significant difference between critical care and control neutrophil function (median 2.8 vs. 1.6, p = 0.752). CONCLUSIONS: Our whole blood neutrophil assay is simple, reproducible and clinically relevant. Changes in neutrophil function measured in this pneumonia cohort is in agreement with previous studies. The assay has potential to be used to identify individuals for clinical trials of immunomodulatory therapies, to risk-stratify patients with pneumonia, and to refine our understanding of 'normal' neutrophil function in infection.

Intracellular alpha-keto acid quantification by fluorescence-HPLC.

Procedures for the analysis of free alpha-keto acids in human fluids (i.e. plasma, cerebrospinal fluid, urine, etc.) as well as for studying the dynamic free alpha-keto acid pools in differentiated tissues and organ cells have been the subject of growing clinical interest in the study of metabolic regulatory and pathophysiological phenomena. Due to the high instability and polarity of the alpha-keto acids being examined, the development of a quantitative and reproducible analysis of metabolically relevant intracellular alpha-keto acids still presents a substantial methodological challenge. The aim of small sample size, rapid, non-damaging and "metabolism-neutral" cell isolation, careful sample preparation and stability, as well as reproducible analytics technology is not often achieved. Only few of the methods described can satisfy the rigorous demands for an ultra-sensitive, comprehensive and rapid intracellular alpha-keto acid analysis.

Which mechanisms are involved in taurine-dependent granulocytic immune response or amino- and alpha-keto acid homeostasis?

We examined the effects of beta-alanine (taurine analogue and taurine transport antagonist), taurine (regarding its role in neutrophil (PMN) immunonutrition) and taurine combined either with L-NAME (inhibitor of *NO-synthase), SNAP (*NO donor), DON (glutamine-analogue and inhibitor of glutamine-requiring enzymes), DFMO (inhibitor of ornithine-decarboxylase) and beta-alanine on neutrophil amino- and alpha-keto acid profiles or important PMN immune functions in order to establish whether taurine transport-, nitric oxide-, glutamine- or ornithine-dependent mechanisms are involved in any of the taurine-induced effects. According to the present findings, the taurine-mediated effect appears to be based primarily on a modulation of important transmembraneous transport mechanisms and only secondarily on directly or indirectly induced modifications in intragranulocytic amino- and alpha-keto acid homoeostasis or metabolism. Although a direct relation to the parallel observed immunological modifications can only be presumed, these results show very clearly that compositional modifications in the free intragranulocytic amino- and alpha keto-acid pools coinciding with changes in intragranulocytic taurine levels are relevant metabolic determinants that can significantly influence the magnitude and quality of the granulocytic immune response.

Comparison of S-(+)-ketamine- with sufentanil-based anaesthesia for elective coronary artery bypass graft surgery: effect on troponin T levels.

BACKGROUND: S-(+)-ketamine anaesthesia carries potential benefits for the cardiovascularly compromised patient. However, the use of S-(+)-ketamine in ischaemic coronary artery disease is controversial. In a prospective, randomized, clinical trial, we have investigated whether an S-(+)-ketamine-based anaesthetic protocol leads to increased cardiac troponin T levels (cTnT) after coronary artery bypass grafting (CABG). METHODS: Two hundred and nine patients undergoing elective CABG were randomized to receive either i.v. anaesthesia with sufentanil-midazolam-propofol (SMP; n=108) or S-(+)-ketamine-midazolam-propofol (KMP; n=101). Haemodynamic variables were maintained within the normal range. Invasive haemodynamic monitoring was performed using a pulmonary artery catheter. Plasma cTnT levels were sampled before induction and 1, 6, and 24 h after aortic unclamping. Cardiovascular adverse events, such as electrocardiographic signs of ischaemia, perioperative myocardial infarction, and death, were recorded. RESULTS: Patient characteristics, cardiac profile, intraoperative management, and the incidence of cardiovascular adverse events were comparable between the groups. Plasma cTnT levels increased after operation in both groups. cTnT levels were significantly lower in the KMP group 6 h after aortic unclamping compared with the SMP group (P=0.004), but did not differ 24 h after aortic unclamping [median (range): SMP 0.4 (0.01-3.9) vs KMP 0.4 (0.07-6.6) microg litre(-1), P=0.338]. CONCLUSIONS: S-(+)-ketamine does not accentuate postoperative cTNT rises in haemodynamically stable elective CABG patients.

Pathways involved in alanyl-glutamine-induced changes in neutrophil amino- and alpha-keto acid homeostasis or immunocompetence.

We examined the effects of DON [glutamine-analogue and inhibitor of glutamine-requiring enzymes], alanyl-glutamine (regarding its role in neutrophil immunonutrition) and alanyl-glutamine combined with L-NAME, SNAP, DON, beta-alanine and DFMO on neutrophil amino and alpha-keto acid concentrations or important neutrophil immune functions in order to establish whether an inhibitor of *NO-synthase [L-NAME], an *NO donor [SNAP], an analogue of taurine and a taurine transport antagonist [beta-alanine], an inhibitor of ornithine-decarboxylase [DFMO] as well as DON could influence any of the alanyl-glutamine-induced effects. In summary, irrespective of which pharmacological, metabolism-inhibiting or receptor-mediated mechanisms were involved, our results showed that impairment of granulocytic glutamine uptake, modulation of intracellular glutamine metabolisation and/or de novo synthesis as well as a blockade of important glutamine-dependent metabolic processes may led to significant modifications of physiological and immunological functions of the affected cells.

Oxygen exchange and C-reactive protein predict safe discharge in patients with H1N1 influenza.

BACKGROUND: : Pandemic influenza has potential to overwhelm healthcare resources. There is uncertainty over performance of existing triage tools for hospital admission and discharge decisions. AIM: : Our aim was to identify clinical criteria that predict safe discharge from hospital and develop a pragmatic triage tool to guide physician decision-making. DESIGN: : We retrospectively examined an existing database of patients who presented to the Royal Liverpool University Hospital during the 2010-11 influenza pandemic. METHODS: Inclusion criteria: patients ≥18 years, with PCR confirmed H1N1 influenza. Exclusion criteria: died in the emergency department or case notes unavailable. Successful discharge was defined as discharge within 24 h of presentation and no readmission within 7 days. RESULTS: Eighty-six patients were included and 16 were successfully discharged. Estimated P/F ratio and C-reactive protein predicted safe discharge in a multivariable logistic regression model (AUC 0.883). A composite univariate predictor (estimated P/F minus C-reactive protein, AUC 0.877) was created to calculate specific cut off points for sensitivity and specificity. A pragmatic decision tool was created to incorporate these thresholds and relevant guidelines. Discharge: SpO 2 (in air) ≥ 94% and CRP <50. Observe: SpO 2 ≥ 94% and CRP >50 or SpO 2 ≤ 93% and CRP <50. Admit: SpO 2 ≤ 93% and CRP >50. CONCLUSIONS: We identified that oxygen exchange and CRP, a marker of acute inflammation, were the most important predictors of safe discharge. Our proposed simple triage model requires validation but has the potential to aid clinical decisions in the event of a future pandemic, and potentially for seasonal influenza.

Endogenous morphine.

It is now well accepted that endogenous morphine is present in animals, both in invertebrates and vertebrates. It is a key signaling molecule that plays an important role in downregulating physiological responses, such as those in the immune system, including immune elements in the CNS. It has been demonstrated that a specific mu-opiate-receptor subtype, mu3, mediates these downregulatory effects through release of NO. This article examines morphine as an endogenous signaling molecule, in terms of its role in neural and immune regulation.

Basal nitric oxide limits immune, nervous and cardiovascular excitation: human endothelia express a mu opiate receptor.

Nitric oxide (NO) is a major signaling molecule in the immune, cardiovascular and nervous systems. The synthesizing enzyme, nitric oxide synthase (NOS) occurs in three forms: endothelial (e), neuronal (n) and inducible (i) NOS. The first two are constitutively expressed. We surmise that in many tissues there is a basal level of NO and that the actions of several signaling molecules initiate increases in cNOS-derived NO to enhance momentary basal levels that exerts inhibitory cellular actions, via cellular conformational changes. It is our contention that much of the literature concerning the actions of NO really deal with i-NOS-derived NO. We make the case that cNOS is responsible for a basal or 'tonal' level of NO; that this NO keeps particular types of cells in a state of inhibition and that activation of these cells occurs through disinhibition. Furthermore, naturally occurring signaling molecules such as morphine, anandamide, interleukin-10 and 17-beta-estradiol appear to exert, in part, their beneficial physiological actions, i.e., immune and endothelial down regulation by the stimulation of cNOS. In regard to opiates, we demonstrate the presence of a human endothelial mu opiate receptor by RT-PCR and sequence determination, further substantiating the role of opiates in vascular coupling to NO release. Taken together, cNOS derived NO enhances basal NO actions, i.e., cellular activation state, and these actions are further enhanced by iNOS derived NO.

Cell-surface estrogen receptors mediate calcium-dependent nitric oxide release in human endothelia.

BACKGROUND: Although estrogen replacement therapy has been associated with reduction of cardiovascular events in postmenopausal women, the mechanism for this benefit remains unclear. Because nitric oxide (NO) is considered an important endothelium-derived relaxing factor and may function to protect blood vessels against atherosclerotic development, we investigated the acute effects of physiological levels of estrogen on NO release from human internal thoracic artery endothelia and human arterial endothelia in culture. METHODS AND RESULTS: We tested the hypothesis that estrogen acutely stimulates constitutive NO synthase activity in human endothelial cells by acting on a cell-surface receptor. NO release was measured in real time with an amperometric probe. 17beta-Estradiol exposure to internal thoracic artery endothelia and human arterial endothelia in culture stimulated NO release within seconds in a concentration-dependent manner. 17beta-Estradiol conjugated to bovine serum albumin also stimulated NO release, suggesting action through a cell-surface receptor. Tamoxifen, an estrogen receptor inhibitor, antagonized this action. We further showed with the use of dual emission microfluorometry that 17beta-estradiol-stimulated release of endothelial NO was dependent on the initial stimulation of intracellular calcium transients. CONCLUSIONS: Physiological doses of estrogen immediately stimulate NO release from human endothelial cells through activation of a cell-surface estrogen receptor that is coupled to increases in intracellular calcium.

Morphine suppresses complement receptor expression, phagocytosis, and respiratory burst in neutrophils by a nitric oxide and mu(3) opiate receptor-dependent mechanism.

We investigated whether morphine and fentanyl influence surface receptor expression, phagocytic activity and superoxide anion generation of neutrophils in a whole blood flow cytometric assay. Morphine suppressed complement and Fcgamma receptor expression and neutrophil function in a concentration- and time-dependent manner. Morphine-induced changes were similar to those caused by the nitric oxide (NO) donor S-nitroso-N-acetyl-penicillamine and were abolished by preincubation with the NO synthase inhibitor N-nitro-L-arginine as well as naloxone. Fentanyl had no immunosuppressive effects. These results suggest that these neutrophil functions are inhibited by morphine-stimulated NO release mediated by the mu(3) opiate receptor subtype found on immunocytes.

Normothermic versus hypothermic cardiopulmonary bypass: do changes in coagulation differ?

BACKGROUND: The differences between hypothermic and normothermic cardiopulmonary bypass (CPB) on platelet function and endothelial-related coagulation (eg, the thrombomodulin/protein C/protein S system) should be investigated. METHODS: According to a randomized sequence, 30 patients undergoing aortocoronary bypass grafting underwent either hypothermic (rectal temperature, 27 degrees C to 28 degrees C, n = 15) or normothermic CPB (rectal temperature, more than 35 degrees C, n = 15). Arterial blood samples were taken after induction of anesthesia (baseline values), before, during, and immediately after CPB, 5 hours after CPB, and on the morning of the first postoperative day. Circulating thrombomodulin, (free) protein S, protein C, and thrombin/antithrombin III complex were measured from these samples. Platelet function was assessed by aggregometry (turbidometric technique) induced by adenosine diphosphate (2 mumol/L), collagen (4 micrograms/L), and epinephrine (25 mumol/L). RESULTS: Hypothermic patients showed a significantly higher blood loss and need for homologous blood than the normothermic patients. Thrombomodulin plasma level increased more in the hypothermic (from 28 +/- 5 ng/mL to 60 +/- 10 ng/mL) than in the normothermic group (from 28 +/- 7 ng/mL to 41 ng/mL); p < 0.05). Both protein C and (free) protein S were reduced significantly in the hypothermic (protein C, from 88% +/- 25% to 60% +/- 11%; protein S, from 71% +/- 10% to 40% +/- 8%) than in the normothermic patients. Platelet aggregation was significantly more decreased in the hypothermic (adenosine diphosphate, maximum decrease by -43% relative to baseline) than in the normothermic patients (adenosine diphosphate, maximum decrease by -22% relative to baseline). In the hypothermic CPB group, platelet aggregation had recovered incompletely, whereas in the normothermic patients platelet aggregation even slightly exceeded baseline values. CONCLUSIONS: Hypothermic CPB resulted in more pronounced alterations of platelet aggregation and endothelial-related coagulation than normothermic CPB. Plasma levels of soluble thrombomodulin were more increased in hypothermic than in normothermic CPB indicating more extensive endothelial damage or activation associated with hypothermic CPB.

Thrombin generation and activation of the thrombomodulin protein C system in open heart surgery depend on the underlying cardiac disease.

The exposure of blood to foreign surfaces during extracorporeal circulation (ECC) leads to an activation of the coagulation system. In arteriosclerotic patients thrombin activation is increased and plasma fibrinogen is elevated, while protein C levels are reduced. In this study we investigated the influence of different cardiac diseases on ECC-induced thrombin generation and activation of the thrombomodulin-protein C system. Twenty-four patients undergoing either elective coronary artery bypass grafting (CABG) or elective aortic valve replacement (AVR) were included in the study. Blood samples were taken at different time intervals before, during and after ECC, and in the postoperative period. Plasma concentrations of thrombin-antithrombin III-complex (TAT), modified antithrombin (ATM), prothrombin fragment F1+2, free protein S, thrombomodulin, and protein C-antigen were determined by ELISA. Fibrinogen and antithrombin III levels were detected by nephelometry. Both groups were comparable with respect to biometric and ECC-related data. TAT concentrations were elevated in both groups after induction and increased during surgery (p<0.001). As a marker of thrombin generation levels of F1+2 were higher in the CABG group during cardiopulmonary bypass (p=0.003). In CABG patients ATM peaks were higher during ECC (p=0.0024). Significantly higher plasma thrombomodulin concentrations were found in CABG patients after induction (p<0.001), while protein S concentrations were higher in the AVR group (p=0.002). Protein C levels and antithrombin III concentrations did not differ between the groups. Patients undergoing CABG were found to have lower protein S levels and increased plasma thrombomodulin concentrations as markers of endothelial damage. In these patients contact activation and as a consequence thrombin generation takes place at a higher level, indicating a hypercoagulable state. Thromboembolic events in the perioperative period may be caused by different hemostatic changes in CABG patients.

The influence of acute preoperative plasmapheresis on coagulation tests, fibrinolysis, blood loss and transfusion requirements in cardiac surgery.

OBJECTIVE: Withdrawal of autologous plasma and reinfusion after cardiopulmonary bypass (CPB) offers the opportunity of improving patients' haemostasis and reducing homologous blood consumption in cardiac surgery. The influence of acute, preoperative plasmapheresis (APP) on coagulation tests, fibrinolysis, blood loss and transfusion requirements was investigated in elective aortocoronary bypass patients. METHODS: Forty patients were randomized to a control or pheresis group. The pheresis group had platelet-rich plasmapheresis (PRP-group, n = 20) performed before incision and the platelet-rich plasma (PRP) was returned after CPB. The control group (n = 20) was managed without pheresis. All patients had serial coagulation studies, including prothrombin split products (F1/F2), fibrinopeptide A (FPA), protein C (PC), thrombomodulin (TM), tissue-plasminogen-activator (t-PA), plasminogen-activator-inhibitor (PAI 1), fibrinopeptide B beta 15-42 (FPB beta 15-42), haemoglobin and platelet counts determined intra- and postoperatively. Chest tube drainage and transfusion requirements were recorded. RESULTS: APP had no negative effects on the quality of PRP. The platelet count of the withdrawn autologous plasma was 239 +/- 33 x 10(9)/l. From the end of the operation (after retransfusion of autologous plasma) until the first postoperative day platelet counts were significant higher in the PRP-group (P > 0.05). Plasma concentrations of modified antithrombin III (ATM), F1/F2 and FPA increased (166-290% from baseline) and PC- and TM-antigen decreased (11-49% from baseline) to a different extent for both groups throughout CPB. t-PA-activity increased intraoperatively peaking at the end of CPB (PRP-group: 4.8 +/- 0.8 IU/ml, control-group: 8.1 +/- 2.3 IU/ml)(P > 0.05). With onset of CPB PAI-1 levels decreased and were further reduced after CPB in control patients in comparison to PRP-patients (P < 0.05). FPB beta 15-42 occurred in peak concentrations after neutralisation of heparin by protamine. Only PRP-patients showed baseline values of coagulation and fibrinolytic parameters on the next morning (P < 0.05). Total postoperative blood loss during the first 24 h was 503 +/- 251 ml (PRP-group) and 937 +/- 349 ml in the control-group (P < 0.05). None of the PRP-patients received allogeneic blood, whereas five control-patients received 11 units of packed red cells (P < 0.05). CONCLUSIONS: The findings suggest that in elective cardiac surgery heparin cannot prevent generation of both thrombin and fibrin, born throughout CPB and postoperatively. The use of PRP withdrawn immediately preoperatively is an attractive technique to reduce allogeneic blood usage and preoperative blood loss, especially in patients in whom withdrawal of autologous whole blood cannot be performed.