Marcin Wasowicz

Platelet transfusions are not associated with increased morbidity or mortality in cardiac surgery.

PurposeTo determine the independent relationship between leukoreduced platelet transfusions and adverse events in cardiac surgery.MethodsIn this observational study, detailed baseline and perioperative data were prospectively collected on consecutive patients who underwent cardiac surgery at a single institution from 1999 to 2004. The independent associations of platelet transfusion with clinical outcomes (low output syndrome, myocardial infarction, stroke, renal failure, sepsis, and death) were determined by multivariable logistic regression analysis and propensity score case-control analysis.ResultsOf the 11,459 patients analyzed, 2,174 (19%) received (leukoreduced) platelets -1,408 received 5 U, 471 received 10 U, 140 received 15 U, and 155 received 20 or more units. Although all measured adverse event rates were higher in those who received platelets, in neither the logistic regression analyses nor the propensity score analyses was there any association between platelet transfusion and any of the adverse events.ConclusionsTransfusion of leukoreduced platelets in cardiac surgery is not associated with adverse clinical outcomes when adjustments are made for important confounders.RésuméObjectifDéterminer la relation indépendante entre la transfusion de plaquettes réduites en leucocytes et les événements indésirables en cardiochirurgie.MéthodeDans une étude par observation, la cueillette prospective des données initiales et périopératoires détaillées a été faite pour des patients successivement opérés en cardiochirurgie dans un seul établissement entre 1999 et 2004. Les associations indépendantes entre transfusion plaquettaire et résultat clinique (syndrome de bas débit, infarctus du myocarde, accident vasculaire, insuffisance rénale, septicémie et mort) ont été déterminées par une analyse multivariée de régression logistique et une analyse cas-témoins du score de propension.RésultatsDes 11 459 patients analysés, 2 174 (19 %) ont reçu des plaquettes réduites en leucocytes -1 408 ont eu 5 U, 471 ont eu 10 U, 140 ont eu 15 U et 155 ont eu 20 unités ou plus. Tous les taux ďévénements indésirables mesurés étaient plus élevés chez ceux qui avaient reçu des plaquettes, mais ni éanalyse de régression logistique ni éanalyse du score de propension n’ont montré ďassociation entre la transfusion de plaquettes et éun des événements indésirables.ConclusionEn cardiochirurgie, la transfusion de plaquettes réduites en leucocytes n’est pas associée à des complications cliniques quand ďimportants facteurs de confusion sont corrigés.Objectif Determiner la relation independante entre la transfusion de plaquettes reduites en leucocytes et les evenements indesirables en cardiochirurgie.

Determinants of complications with recombinant factor VIIa for refractory blood loss in cardiac surgery

PurposeRecombinant factor VIIa (rFVIIa) is being used for refractory, excessive blood loss (EBL) after cardiac surgery, but its safety for this indication is not known.MethodsThe unadjusted and risk-adjusted adverse event (AE) rates were compared between 114 consecutive cardiac surgical patients who received rFVIIa for refractory EBL and 541 concurrent patients who developed EBL but did not receive rFVIIa. Similarly, timing of rFVIIa therapy was assessed by dichotomizing rFVIIa patients based on median number of red blood cell (RBC) units received before therapy. The measured AE was a composite of death, stroke, renal failure, myocardial infarction, and major vein thrombosis. For risk adjustment, logistic regression models for this outcome were constructed using known predictors of AEs.ResultsThe median RBC units transfused before rFVIIa therapy was eight. The AE rates in the untreated, early (≤ 8 U), and late (> 8 U) treated patients were 24% (129/541), 30% (20/66), and 60% (29/48). The risk-adjustment model included total RBC units, pump time, weaning difficulty, gender, weight, and age. The unadjusted and adjusted AE odds ratios (OR) in the treatedvs untreated groups were 2.41 [confidence interval (CI) 1.58 -3.67;P < 0.0001 ] and 1.04 (CI 0.60 — 1.81 ;P = 0.9). In the rFVIIa group, the adjusted AE OR was lower in the early treated group (OR 0.41; CI 0.18 — 0.92;P = 0.03).ConclusionIn cardiac surgical patients with refractory hemorrhage, rFVIIa therapy is not associated with increased risk of AEs, and early treatment may be associated with better outcomes.RésuméObjectifLe facteur VIIa recombinant (rFVIIa) est utilisé pour traiter les pertes sanguines excessives (PSE) réfractaires après une opération cardiaque sans qu’on en connaisse l’innocuité.MéthodeLes taux d’événements indésirables (EI) non ajustés et ajustés en fonction des risques ont été comparés entre 114 patients consécutifs de cardiochirurgie ayant reçu le rFVIIa pour des PSE et 541 patients consécutifs qui ont eu des PSE mais pas de rFVIIa. De même, la programmation du traitement au rFVIIa a été étudiée par une division dichotomique des patients, recevant le rFVIIa, fondée sur le nombre médian d’unités de culots globulaires (CG) reçues avant le traitement. Les EI étaient la mort, l’accident vasculaire, l’insuffisance rénale, l’infarctus du myocarde et la thrombose veineuse majeure. Des modèles de régression logistique ont été construits pour ajuster le risque en utilisant les prédicteurs connus d’EI.RésultatsLa médiane des unités de CG transfusées avant le traitement au rFVIIa a été de huit. Les taux d’EI chez les patients non traités, traités tôt (≤ 8 U) et tard (> 8 U) ont été de 24 % (129/541), 30 % (20/66) et 60 % (29/48). Le modèle d’ajustement du risque comprenait le nombre total d’unités de CG, le temps de perfusion, les difficultés de sevrage, le sexe, le poids et l’âge. Les risques relatifs (RR) d’EI non ajustés et ajustés chez les patients traités vs non traités ont été de 2,41 [intervalle de confiance (IC) de 1,58 -3,67 ;P< 0,0001] et 1,04 (IC 0,60-1,81 ;P = 0,9). Dans le groupe rFVIIa, le RR d’EI ajusté a été plus bas chez les patients traités tôt (RR 0,41 ; IC 0,18 — 0,92 ; P = 0,03).ConclusionChez les patients de cardiochirurgie victimes d’hémorragie réfractaire, le traitement au rFVIIa n’est pas associé

The role of point-of-care platelet function testing in predicting postoperative bleeding following cardiac surgery: a systematic review and meta-analysis†

This systematic review and meta‐analysis appraises the utility of point‐of‐care platelet function tests for predicting blood loss and transfusion requirements in cardiac surgical patients, and analyses whether their use within a transfusion management algorithm is associated with improved patient outcomes. We included 30 observational studies incorporating 3044 patients in the qualitative assessment, and nine randomised controlled trials including 1057 patients in the meta‐analysis. Platelet function tests demonstrated significant variability in their ability to predict blood loss and transfusion requirements. Their use within a blood transfusion algorithm demonstrated a reduction in blood loss at longest follow‐up (mean difference −102.9 ml (95% CI −149.9 to −56.1 ml), p < 0.001), and transfusion of packed red cells (RR 0.86 (95% CI 0.78−0.94), p = 0.001) and fresh frozen plasma (RR 0.42 (95% CI 0.30−0.59), p < 0.001). Viscoelastic methods used in combination with other platelet function tests achieved greater reduction in blood loss (mean difference −111.8 ml (95% CI −174.9 to −49.1 ml), p = 0.0005) compared with their use alone (mean difference −90.6 ml (95% CI 166.1−15.0 ml), p = 0.02). We conclude that incorporation of point‐of‐care platelet function tests into transfusion management algorithms is associated with a reduction in blood loss and transfusion requirements in cardiac surgery patients.

La transfusion de plaquettes n’est pas associée à une hausse de la morbidité ou de la mortalité en cardiochirurgie

PurposeTo determine the independent relationship between leukoreduced platelet transfusions and adverse events in cardiac surgery.MethodsIn this observational study, detailed baseline and perioperative data were prospectively collected on consecutive patients who underwent cardiac surgery at a single institution from 1999 to 2004. The independent associations of platelet transfusion with clinical outcomes (low output syndrome, myocardial infarction, stroke, renal failure, sepsis, and death) were determined by multivariable logistic regression analysis and propensity score case-control analysis.ResultsOf the 11,459 patients analyzed, 2,174 (19%) received (leukoreduced) platelets -1,408 received 5 U, 471 received 10 U, 140 received 15 U, and 155 received 20 or more units. Although all measured adverse event rates were higher in those who received platelets, in neither the logistic regression analyses nor the propensity score analyses was there any association between platelet transfusion and any of the adverse events.ConclusionsTransfusion of leukoreduced platelets in cardiac surgery is not associated with adverse clinical outcomes when adjustments are made for important confounders.RésuméObjectifDéterminer la relation indépendante entre la transfusion de plaquettes réduites en leucocytes et les événements indésirables en cardiochirurgie.MéthodeDans une étude par observation, la cueillette prospective des données initiales et périopératoires détaillées a été faite pour des patients successivement opérés en cardiochirurgie dans un seul établissement entre 1999 et 2004. Les associations indépendantes entre transfusion plaquettaire et résultat clinique (syndrome de bas débit, infarctus du myocarde, accident vasculaire, insuffisance rénale, septicémie et mort) ont été déterminées par une analyse multivariée de régression logistique et une analyse cas-témoins du score de propension.RésultatsDes 11 459 patients analysés, 2 174 (19 %) ont reçu des plaquettes réduites en leucocytes -1 408 ont eu 5 U, 471 ont eu 10 U, 140 ont eu 15 U et 155 ont eu 20 unités ou plus. Tous les taux ďévénements indésirables mesurés étaient plus élevés chez ceux qui avaient reçu des plaquettes, mais ni éanalyse de régression logistique ni éanalyse du score de propension n’ont montré ďassociation entre la transfusion de plaquettes et éun des événements indésirables.ConclusionEn cardiochirurgie, la transfusion de plaquettes réduites en leucocytes n’est pas associée à des complications cliniques quand ďimportants facteurs de confusion sont corrigés.Objectif Determiner la relation independante entre la transfusion de plaquettes reduites en leucocytes et les evenements indesirables en cardiochirurgie.

Technical report: Analysis of citrated blood with thromboelastography: comparison with fresh blood samples

Purpose: Thromboelastography (TEG) evaluates the viscoelastic properties of whole blood to assess clot formation and hemostasis. When blood cannot be analyzed immediately, it is stored in citrated tubes to be analyzed after recalcification. In this study, we evaluated the results of TEG analysis performed on citrated blood and compared these results to values obtained from activated (kaolin and tissue factor) and non activated, fresh blood samples, obtained at various time intervals (one, two, and three hours).Methods: Four blood samples were collected from each of ten healthy volunteers. The following TEG analyses were performed on each sample: reaction time (r), k time (k), alpha angle (α), and maximum amplitude (MA). Studies were done using fresh, non citrated blood, obtained within five minutes of collection, and using citrated blood, one, two, and three hours after collection. Samples were analyzed, with and without activation, using kaolin and tissue factor.Results: Tissue factor activated and non activated, citrated samples had shorter r and k times (P=0.03,P=0.008,P<0.0001, andP<0.0001, respectively) and higher alpha angle and MA values (P<0.0001,P<0.0001,P=0.79, andP=0.03, respectively) compared to fresh, non citrated samples. These findings were consistent with a hypercoagulable state. Conversely, citrated samples, activated with kaolin, yielded results similar to those obtained from fresh, non citrated samples. The TEG measurements were similar among citrated samples stored from one to three hours.Conclusions: Our results demonstrate that TEG measures, performed on citrated blood samples, yield results that are consistent with a hyperocoagulable state. Using kaolin to activate citrated samples, on the other hand, yields results similar to those obtained from non citrated, fresh blood samples.RésuméObjectif: La thromboélastographie (TEG) évalue les propriétés viscoélastiques du sang complet afin d’évaluer la formation de caillots et l’hémostase. Lorsque le sang ne peut pas être immédiatement analysé, il est stocké dans des tubes citratés afin d’être analysé après recalcification. Dans cette étude, nous avons évalué les résultats d’analyse TEG obtenus sur des échantillons de sang citraté et avons comparé ces résultats aux valeurs obtenues à partir d’échantillons de sang frais, activé (kaolin et facteur tissulaire) et non activé, lesquels avaient été obtenus à différents intervalles de temps (une, deux et trois heures).Méthode: Dix volontaires sains ont chacun donné quatre échantillons de sang. Les analyses TEG suivantes ont été effectuées sur chaque échantillon : temps de réaction (r), temps k (k), angle alpha (α) et amplitude maximale (MA). Des études ont été faites avec du sang frais et non citraté dans les cinq minutes suivant son obtention, ainsi qu’avec du sang citraté une, deux et trois heures après la collecte. Les échantillons ont été analysés avec ou sans activation à l’aide de kaolin et de facteur tissulaire.Résultats: Les échantillons citratés activés et non activés avec le facteur tissulaire ont présenté des temps r et k (P=0,03, P=0,008, P<0,0001, et P<0,0001, respectivement) plus courts ainsi qu’un angle alpha et des valeurs MA plus élevés (P<0,0001, P<0,0001, P=0,79, et P=0,03, respectivement) que les échantillons frais et non citratés. Ces résultats coïncident avec un état hypercoagulable. En revanche, les échantillons citratés activés avec kaolin ont donné des résultats similaires à ceux obtenus à partir d’échantillons frais non citratés. Les mesures TEG étaient semblables pour les échantillons citratés stockés de une à trois heures.Conclusion: Nos résultats démontrent que les mesures TEG, effectuées sur des échantillons de sang citratés, donnent des résultats qui coïncident avec un état hypercoagulable. L’utilisation de kaolin pour activer des échantillons citratés, en revanche, donne des résultats similaires à ceux obtenus d’échantillons de sang frais non citraté.

The association between tranexamic acid and convulsive seizures after cardiac surgery: a multivariate analysis in 11 529 patients

Because of a lack of contemporary data regarding seizures after cardiac surgery, we undertook a retrospective analysis of prospectively collected data from 11 529 patients in whom cardiopulmonary bypass was used from January 2004 to December 2010. A convulsive seizure was defined as a transient episode of disturbed brain function characterised by abnormal involuntary motor movements. Multivariate regression analysis was performed to identify independent predictors of postoperative seizures. A total of 100 (0.9%) patients developed postoperative convulsive seizures. Generalised and focal seizures were identified in 68 and 32 patients, respectively. The median (IQR [range]) time after surgery when the seizure occurred was 7 (6–12 [1–216]) h and 8 (6–11 [4–18]) h, respectively. Epileptiform findings on electroencephalography were seen in 19 patients. Independent predictors of postoperative seizures included age, female sex, redo cardiac surgery, calcification of ascending aorta, congestive heart failure, deep hypothermic circulatory arrest, duration of aortic cross‐clamp and tranexamic acid. When tested in a multivariate regression analysis, tranexamic acid was a strong independent predictor of seizures (OR 14.3, 95% CI 5.5–36.7; p < 0.001). Patients with convulsive seizures had 2.5 times higher in‐hospital mortality rates and twice the length of hospital stay compared with patients without convulsive seizures. Mean (IQR [range]) length of stay in the intensive care unit was 115 (49–228 [32–481]) h in patients with convulsive seizures compared with 26 (22–69 [14–1080]) h in patients without seizures (p < 0.001). Convulsive seizures are a serious postoperative complication after cardiac surgery. As tranexamic acid is the only modifiable factor, its administration, particularly in doses exceeding 80 mg.kg−1, should be weighed against the risk of postoperative seizures.

The interaction of carbon dioxide and hypoxia in the control of cerebral blood flow.

Both hypoxia and carbon dioxide increase cerebral blood flow (CBF), and their effective interaction is currently thought to be additive. Our objective was to test this hypothesis. Eight healthy subjects breathed a series of progressively hypoxic gases at three levels of carbon dioxide. Middle cerebral artery velocity, as an index of CBF; partial pressures of carbon dioxide and oxygen and concentration of oxygen in arterial blood; and mean arterial blood pressure were monitored. The product of middle cerebral artery velocity and arterial concentration of oxygen was used as an index of cerebral oxygen delivery. Two-way repeated measures analyses of variance (rmANOVA) found a significant interaction of carbon dioxide and hypoxia factors for both CBF and cerebral oxygen delivery. Regression models using sigmoidal dependence on carbon dioxide and a rectangular hyperbolic dependence on hypoxia were fitted to the data to illustrate this interaction. We concluded that carbon dioxide and hypoxia act synergistically in their control of CBF so that the delivery of oxygen to the brain is enhanced during hypoxic hypercapnia and, although reduced during normoxic hypocapnia, can be restored to normal levels with progressive hypoxia.

The incremental value of thrombelastography for prediction of excessive blood loss after cardiac surgery: an observational study.

BACKGROUND: Accurate risk stratification may help reduce the burden of excessive blood loss after cardiac surgery. We measured the incremental value of thrombelastography to an existing risk prediction model for excessive blood loss in cardiac surgery. METHODS: This observational study included 434 patients who underwent cardiac surgery with cardiopulmonary bypass (CPB) and had thrombelastographic measures before and during CPB, their risk of excessive blood loss could be calculated with an existing risk prediction model and they had not received clopidogrel or warfarin within 5 days of surgery. Excessive blood loss was defined as transfusion of ≥5 U of red blood cells from termination of CPB to 1 day after surgery. Logistic regression models including an existing risk prediction model without and with thrombelastographic measures were constructed. Improvement in risk prediction was measured by the area under the curve and net reclassification improvement. RESULTS: Excessive blood loss occurred in 59 of 434 patients (13.6%). The only thrombelastographic measure that improved risk stratification was maximum amplitude during CPB, which reflects maximum clot strength. Although the addition of this variable to the existing prediction model did not have a material effect on the area under the curve (increased from 0.780 to 0.784; P = 0.8), it did improve the net reclassification improvement by 12% (P = 0.05), primarily by improving the detection of high-risk cases. CONCLUSIONS: Risk stratification for excessive blood loss after cardiac surgery is improved when on-CPB thrombelastography is added to an existing risk prediction model that incorporates readily available patient- and surgery-related variables, but large, multicenter trials are needed to verify this finding and create a new risk prediction model.

Tranexamic acid: a clinical review

Blood loss and subsequent transfusions are associated with major morbidity and mortality. The use of antifibrinolytics can reduce blood loss in cardiac surgery, trauma, orthopedic surgery, liver surgery and solid organ transplantation, obstetrics and gynecology, neurosurgery and non-surgical diseases. The evidence of their efficacy has been mounting for years. Tranexamic acid (TXA), a synthetic lysine-analogue antifibrinolytic, was first patented in 1957 and its use has been increasing in contrast to aprotinin, a serine protease inhibitor antifibrinolytic. This review aims to help acute care physicians navigate through the clinical evidence available for TXA therapy, develop appropriate dose regimens whilst minimizing harm, as well as understand its broadening scope of applications. Many questions remain unanswered regarding other clinical effects of TXA such as anti-inflammatory response to cardiopulmonary bypass, the risk of thromboembolic events, adverse neurological effects such as seizures, and its morbidity and mortality, all of which necessitate further clinical trials on its usage and safety in various clinical settings.

Bivalirudin anticoagulation for cardiopulmonary bypass in a patient with heparin-induced thrombocytopenia.

PurposeTo describe the perioperative management in a heparin-induced thrombocytopenia (HIT) positive patient who had prosthetic valve endocarditis and an aortic root abscess. The patient underwent high-risk cardiac re-operation with the use of the alternative anticoagulant, bivalirudin.Clinical featuresA 62-yr-old patient who underwent stentless tissue aortic valve replacement with a Toronto-SPV valve in 1998, was admitted to hospital with symptoms of stroke. A heparin infusion was started and further investigation revealed positive blood cultures. The patient developed HIT which was confirmed by laboratory tests. Echocardiographic examination performed one month later showed vegetations on the aortic tissue valve and a small aortic root abscess. The patient still tested positively for the presence of HIT antibodies and was treated conservatively with antibiotics. A repeat echocardiographic examination showed progression of the aortic root abscess and it was decided to proceed with urgent redo aortic valve surgery. Anticoagulation for cardiopulmonary bypass (CPB) was achieved with the use of a direct thrombin inhibitor (DTI), bivalirudin. Following an uneventful wean from CPB, hemostasis was achieved within 40 min. The postoperative course was uncomplicated and the patient was discharged from hospital on the seventh postoperative day.ConclusionBivalirudin is a DTI, which can be used as an alternative anticoagulant for CPB in HIT positive patients. This case report showed a favourable outcome with bivalirudin for urgent complex redo cardiac surgery requiring CPB.RésuméObjectifDécrire la prise en charge périopératoire ďun patient atteint de TIH, victime ďune endocardite sur prothèse valvulaire et ďun abcès à la racine de ľaorte. Le patient a subi une réopération cardiaque à haut risque avec ľusage ďanticoagulant de remplacement, la bivalirudine.Éléments cliniquesUn patient de 62 ans chez qui on a remplacé le tissu de la valve aortique, sans endoprothèse, par une valve Toronto-SPV en 1998 a été admis à ľhôpital pour des symptômes ďaccident vasculaire cérébral. Une perfusion ďhéparine a été amorcée et un examen ultérieur a révélé des cultures sanguines positives. Une TIH s’est développée et a été confirmée par les tests de laboratoire. Ľéchocardiographie, réalisée un mois plus tard, a montré des végétations sur la valve tissulaire aortique et un petit abcès à la racine de ľaorte. Les résultats aux tests indiquant toujours la présence ďanticorps de TIH, le patient a reçu une antibiothérapie conservatrice. Une nouvelle échocardiographie a montré la progression de ľabcès aortique, ce qui a conduit à répéter ďurgence ľopération de la valve aortique. Ľanticoagulation pour la circulation extracorporelle (CEC) a été réalisée avec un inhibiteur direct de la thrombine (IDT), la bivalirudine. Après un sevrage sans incident de la CEC, ľhémostase a été atteinte en moins de 40 min. Aucune complication n’est survenue par la suite et le patient a quitté ľhôpital au septième jour postopératoire.ConclusionLa bivalirudine est un IDT qui peut être utilisé comme anticoagulant de remplacement pendant la CEC chez des patients victimes de TIH.