Topical moistening of mastectomy wounds with diluted tranexamic acid to reduce bleeding: randomized clinical trial.

BACKGROUND: Topical administration of tranexamic acid (TXA) may be an alternative to intravenous administration to reduce bleeding with a lower risk of systemic adverse events. The aim of this study was to investigate whether moistening a surgical wound with TXA before closure, leaving a thin film of drug only, would reduce postoperative bleeding. METHODS: This was a two-centre, stratified, parallel-group, placebo-controlled, double-blind RCT. Patients undergoing mastectomy with or without axillary lymph node clearance were randomized 1 : 1 to moistening of wound surface before closure with either 25 mg/ml TXA or 0·9 per cent sodium chloride (placebo). The primary endpoint was postoperative bleeding as measured by drain production in the first 24 h. Secondary endpoints were early haematoma, total drain production, postoperative complications and late aspirations of seroma within 3 months. RESULTS: Between 1 January 2016 and 31 August 2018, 208 patients were randomized. Two patients were converted to a different surgical procedure at surgery, and four did not receive the intervention owing to technical error. Thus, 202 patients were included in the study (101 in the TXA and 101 in the placebo group). TXA reduced mean drain production at 24 h (110 versus 144 ml; mean difference 34 (95 per cent c.i. 8 to 60) ml, P = 0·011). One patient in the TXA group had early haematoma compared with seven in the placebo group (odds ratio (OR) 0·13 (95 per cent c.i. 0·02 to 1·07); P = 0·057). There was no significant difference in postoperative complications between TXA and placebo (13 versus 10; OR 1·11 (0·45 to 2·73), P = 0·824) or need for late seroma aspirations (79 versus 67 per cent; OR 1·83 (0·91 to 3·68), P = 0·089). CONCLUSION: Moistening the wound with TXA 25 mg/ml before closure reduces postoperative bleeding within the first 24 h in patients undergoing mastectomy. Registration number: NCT02627560 (https://clinicaltrials.gov).

ANTECEDENTES: La administración tópica de ácido tranexámico (tranexamic acid, TXA) puede ser una alternativa a la administración por vía intravenosa para reducir la hemorragia, con menor riesgo de eventos sistémicos adversos. El objetivo de este estudio fue investigar si humedecer la herida quirúrgica con TXA 25 mg/ml antes del cierre de la incisión dejando solo una fina película de fármaco, reducía la hemorragia postoperatoria. MÉTODOS: Se trata de un ensayo clínico aleatorizado, a doble ciego, controlado con placebo, de grupos paralelos, estratificado por dos centros. Las pacientes sometidas a mastectomía con/sin resección de los ganglios linfáticos axilares se asignaron al azar 1:1 para la humidificación de la superficie de la herida antes del cierre con TXA 25 mg/ml o con NaCl al 0,9% (placebo). El objetivo primario fue la hemorragia postoperatoria medida por el débito del drenaje durante las primeras 24 horas. Los objetivos secundarios fueron el desarrollo de hematoma precoz, el débito total del drenaje, las complicaciones postoperatorias y la necesidad de aspiración de un seroma tardío durante los primeros 3 meses tras la cirugía. RESULTADOS: Entre el 1 de enero de 2016 y el 31 de agosto de 2018, 208 pacientes fueron asignadas al azar. En dos pacientes tuvo que realizarse un procedimiento quirúrgico diferente durante el periodo perioperatorio y cuatro pacientes no recibieron la intervención por errores técnicos. Por lo tanto, se incluyeron 202 pacientes en el estudio (101 fueron tratadas con TXA y 101 con placebo). El TXA redujo el débito medio del drenaje a las 24 horas (110 versus 144 ml, diferencia media 34 ml, i.c. del 95%: 8 a 60 ml, P = 0,010). Se presentó un hematoma precoz en una paciente del grupo del TXA versus siete pacientes tratadas con placebo (razón de oportunidades, odds ratio, OR 0,13, i.c. del 95% 0,02-1,07, P = 0,057). No hubo diferencias significativas en las complicaciones postoperatorias entre TXA y placebo (13 versus 10, OR 1,11, i.c. del 95% 0,45-2,73, P = 0,824) o la necesidad de aspiración tardía de seromas (79,3 versus 66,6%, OR 1,83, i.c. del 95% 0,91-3,68, P = 0,089). CONCLUSIÓN: Humedecer la herida antes del cierre con TXA 25 mg/ml reduce la hemorragia postoperatoria durante las primeras 24 horas en pacientes sometidas a mastectomía.

Randomized clinical trial of topical tranexamic acid after reduction mammoplasty.

BACKGROUND: The antifibrinolytic drug tranexamic acid is currently being rediscovered for both trauma and major surgery. Intravenous administration reduces the need for blood transfusion and blood loss by about one-third, but routine administration in surgery is not yet advocated owing to concerns regarding thromboembolic events. The aim of this study was to investigate whether topical application of tranexamic acid to a wound surface reduces postoperative bleeding. METHODS: This was a randomized double-blind placebo-controlled trial on 30 consecutive women undergoing bilateral reduction mammoplasty. On one side the wound surfaces were moistened with 25 mg/ml tranexamic acid before closure, and placebo (saline) was used on the other side. Drain fluid production was measured for 24 h after surgery, and pain was measured after 3 and 24 h. Postoperative complications including infection, seroma, rebleeding and suture reactions were recorded. RESULTS: Topical application of tranexamic acid to the wound surface after reduction mammoplasty reduced drain fluid production by 39 per cent (median 12·5 (range 0-44) versus 20·5 (0-100) ml; P = 0·038). Adverse effects were not observed. There were no significant differences in postoperative pain scores or complications. CONCLUSION: Topical application of dilute tranexamic acid reduced bleeding in this model. The study adds to the evidence that this simple procedure may reduce wound bleeding after surgery. REGISTRATION NUMBER: NCT01964781 ( http://www.clinicaltrials.gov).

Genetic variation influences the risk of bleeding after cardiac surgery: novel associations and validation of previous findings.

BACKGROUND: Severe post-operative bleeding in cardiac surgery is associated with increased morbidity and mortality. We hypothesized that variation in genetic susceptibility contributes to post-operative bleeding in addition to clinical factors. METHODS: We included 1036 adults undergoing cardiac surgery with cardiopulmonary bypass. Two different endpoints for excessive post-operative bleeding were used, either defined as blood loss exceeding 2 ml/kg/h the first 4 h post-operatively or a composite including bleeding, transfusions, and reoperations. Twenty-two single nucleotide polymorphisms (SNPs) central in the coagulation and fibrinolysis systems or in platelet membrane receptors were genotyped, focusing on replication of earlier non-replicated findings and exploration of potential novel associations. Using logistic regression, significant SNPs were added to a model with only clinical variables to evaluate whether the genetic variables provided additional information. RESULTS: Univariate tests identified rs1799809 (located in the promoter region of the PROC gene), rs27646 and rs1062535 (in the ITGA2 gene), rs630014 (in the ABO gene), and rs6048 (in the F9 gene) as significantly associated with excessive post-operative bleeding (P < 0.05, P-values confirmed by permutation). The SNPs were significant also after adjustment with clinical variables, showing almost unchanged odds ratios except for rs1799809 (P = 0.06). Addition of the genetic covariates to a logistic regression model with clinical variables significantly improved the model (P < 0.01). CONCLUSION: We identified five SNPs associated with post-operative bleeding after cardiac surgery, of which two validated previously published associations. Addition of genetic information to models with only clinical variables improved the models. Our results indicate that common genetic variations significantly influence post-operative bleeding after cardiac surgery.

Genetic and clinical risk factors for fluid overload following open-heart surgery.

BACKGROUND: Post-operative fluid overload following cardiac surgery is associated with increased morbidity and mortality. We hypothesised that genetic variations and pre-operative clinical factors predispose some patients to post-operative fluid overload. METHODS: Perioperative variables were collected prospectively for 1026 consecutive adults undergoing open-heart surgery at St. Olavs University Hospital, Norway from 2008-2010. Post-operative fluid overload was defined as a post-operative fluid balance/kg ≥ the 90th percentile of the study population. Genotyping was performed for 31 single-nucleotide polymorphisms related to inflammatory/vascular responses or previously associated with complications following open-heart surgery. Data were analysed using logistic regression modelling, and the findings were internally validated by bootstrapping (n = 100). RESULTS: Homozygous carriers of the common G allele of rs12917707 in the UMOD gene had a 2.2 times greater risk of post-operative fluid overload (P = 0.005) after adjustment for significant clinical variables (age, duration of cardiopulmonary bypass, and intraoperative red cell transfusion). A genetic risk score including 14 single-nucleotide polymorphisms was independently associated with post-operative fluid overload (P = 0.001). The number of risk alleles was linearly associated with the frequency of fluid overload (odds ratio per risk allele 1.153, 95 % confidence interval 1.056-1.258). Nagelkerke's R(2) increased with 7.5% to a total of 25% for the combined clinical and genetic model. Hemofiltration did not reduce the risk. CONCLUSION: A common variation in the UMOD gene previously shown to be related to renal function was associated with increased risk of post-operative fluid overload following cardiac surgery. Our findings support a genetic susceptibility to disturbed fluid handling following cardiac surgery.

Pre-operative and intraoperative determinants for prolonged ventilation following adult cardiac surgery.

BACKGROUND: Prolonged ventilation is a serious complication after cardiac surgery, but few risk prediction models exist. Our objectives were to develop a specific risk prediction model based on pre-operative variables, to identify whether selected intraoperative variables could improve prediction, and to compare our model with the EuroSCORE. METHODS: Data from 5027 patients undergoing open-heart surgery in 2000-2007 were used for logistic regression model development. Internal validation was performed by bootstrapping. Discrimination and calibration were assessed with areas under the receiver operating characteristic curve (AUC) and the Hosmer-Lemeshow test. Our pre-operative model was compared with predictions based on the additive and logistic EuroSCORE. RESULTS: Age, previous cardiac surgery, peripheral arterial disease, left ventricular hypertrophy, chronic pulmonary disease, renal insufficiency, pre-operative hemoglobin concentration, urgent or emergency operation, and operation other than isolated coronary artery bypass grafting were identified as pre-operative predictors for prolonged ventilation (model I). Discrimination and accuracy were excellent (AUC: 0.848 and shrinkage factor: 94%). Calibration was good (Hosmer-Lemeshow test: P = 0.43). Inclusion of a few intraoperative variables somewhat improved the model, increasing shrinkage factors (96%) and discrimination ability (AUC model II = 0.870 and model III = 0.875 for two alternative such models). Our pre-operative model showed better performance than the logistic or additive EuroSCORE. CONCLUSIONS: The pre-operative risk prediction model for prolonged ventilation with easily obtainable variables in routine clinical work performed well and was only slightly improved by inclusion of intraoperative variables. Performance was better than with the EuroSCORE.

Mortality risk prediction in cardiac surgery: comparing a novel model with the EuroSCORE.

BACKGROUND: Several models for prediction of early mortality after open-heart surgery have been developed. Our objectives were to develop a local mortality risk prediction model, compare it with the European System for Cardiac Operative Risk Evaluation (EuroSCORE), and investigate whether the addition of intra-operative variables could enhance the accuracy of risk prediction. METHODS: All 5029 patients undergoing open-heart surgery in 2000-2007 were included in the study. Logistic regression with bootstrap methods was used to develop a pre-operative risk prediction model for in-hospital mortality. Next, several intra-operative variables were added to the pre-operative model. Calibration and discrimination were assessed, and the model was internally validated for prediction in future datasets. We thereafter compared the pre-operative model with the additive and logistic EuroSCOREs. RESULTS: Our pre-operative model included eight risk factors that are routinely registered in our department: age, gender, degree of urgency, operation type, previous cardiac surgery, and renal, cardiac, and pulmonary dysfunction. The model estimated mortality accurately throughout the dataset except in the 1% of patients at extremely high risk, in which mortality was somewhat overestimated. The estimated shrinkage factor was 0.930. The areas under the receiver operating characteristic curve for our pre-operative model and the logistic EuroSCORE were 0.857(0.823-0.891) and 0.821(0.785-0.857) (P=0.02). There was no significant difference in performance between the pre-operative and the intra-operative model (P>0.10). CONCLUSION: Our pre-operative model was simple and easy to use, and showed good predictive ability in our population. Internal validation indicated that it would accurately predict mortality in a future dataset.

Sonoclot analysis in elderly compared with younger patients undergoing coronary surgery.

BACKGROUND: The Sonoclot analyzer is a point-of-care method for assessment of the clotting mechanism in whole blood. The results are available within 20 min. The aim of the present study was to investigate whether repeated Sonoclot analyses could identify peri-operative differences in hemostatic function between elderly and younger patients undergoing coronary artery bypass grafting (CABG). In addition, we investigated whether Sonoclot analyses could identify disturbances in hemostatic function leading to post-operative bleeding. METHODS: Twenty-five elderly and 25 younger patients undergoing CABG were included. Blood samples for Sonoclot analyses were drawn pre-operatively, during surgery, and during the first 20 post-operative hours. The Sonoclot variables sonACT, clot rate, time-to-peak, amplitude of the peak, and R3 were analyzed, and the results were compared between the two groups. Post-operative blood loss volumes were recorded and correlated to the Sonoclot variables. The Sonoclot variables were also correlated to previously reported results on various hemostatic variables measured in the same patient population. RESULTS: There was a significant difference in sonACT between the two groups (P=0.018). There were no differences between the groups in any of the other Sonoclot variables. There were no significant correlations between any of the Sonoclot variables and post-operative bleeding, or between the Sonoclot variables and other hemostatic variables. CONCLUSIONS: The difference in sonACT between the two groups indicates a reduced hemostatic function in the elderly patients. However, repeated Sonoclot analyses were not able to identify more specific disturbances in hemostatic function, and did not predict increased post-operative bleeding.

Effects of autotransfusion of mediastinal shed blood on biochemical markers of myocardial damage in coronary surgery.

BACKGROUND: Previous studies have shown conflicting results regarding the effect of autotransfusion of mediastinal shed blood after coronary artery bypass grafting (CABG) on the serum levels of myocardial band (MB) isoenzymes of creatine kinase (CK-MB) and cardiac troponins. The effect of autotransfusion on serum levels of human heart fatty acid binding protein (H-FABP), another marker of myocardial necrosis, has not been studied. The aim of the present study was to investigate the effects of autotransfusion of mediastinal shed blood on the serum levels of CK-MB, cardiac troponin T (cTnT), and H-FABP after uncomplicated primary CABG. METHODS: Fifty patients were randomized to post-operative autotransfusion of mediastinal shed blood or no autotransfusion. Blood samples for the analysis of the biochemical markers of myocardial damage were drawn pre-operatively and 1, 4, 12, 24, 48, and 72 h after the termination of cardiopulmonary bypass. Samples from the mediastinal shed blood were collected after 1 and 4 h. RESULTS: The levels of the biochemical markers of myocardial injury were all markedly elevated in mediastinal shed blood. Autotransfusion did not significantly affect the serum levels of cTnT or H-FABP. However, during the early post-operative hours, there was a trend towards a higher level of cTnT and H-FABP in the autotransfusion group. During the first 24 h after surgery, the autotransfusion group had a significantly higher serum level of CK-MB. CONCLUSION: Post-operative autotransfusion of mediastinal shed blood may contribute to elevated serum levels of biochemical markers of myocardial injury.

Supplemental remifentanil during coronary artery bypass grafting is followed by a transient postoperative cardiac depression.

BACKGROUND: The pharmacokinetic properties of the short-acting micro opioid receptor-agonist remifentanil makes it possible to give cardiac surgical patients a deep intraoperative anesthesia without experiencing postoperative respiratory depression and a prolonged stay in the intensive care unit (ICU). However, previous investigations have shown that patients who received remifentanil required additional analgesia during the early postoperative period as compared to patients who received fentanyl. The aim of the present study therefore was to investigate the effects of supplementing remifentanil to a standard fentanyl-based anesthesia in coronary artery bypass grafting (CABG). METHODS: The study was prospective, randomized, double-blind, and placebo-controlled. Twenty male patients aged 55-70 years were included. All patients received a standard fentanyl and isoflurane-based anesthesia. In addition, the patients were randomized to receive either remifentanil 0.5 micro g kg(-1) min(-1) or placebo during surgery. Hemodynamic recordings and measurements of blood glucose and plasma adrenaline and noradrenaline were performed intra- and postoperatively. RESULTS: Remifentanil reduced the hemodynamic and metabolic response to surgical stress compared to the standard fentanyl-based anesthetic regimen. However, the patients in the remifentanil group had a lower cardiac output (CO), left ventricular stroke work index (LVSWI), and mixed venous oxygen saturation (SvO(2)), and a higher central venous pressure (CVP) than the patients in the placebo group during the early postoperative phase, indicating a postoperative cardiac depression in the remifentanil group. CONCLUSION: In CABG, remifentanil reduces the hemodynamic and metabolic responses during surgery but seems to give a cardiac depression in the early postoperative phase.

Gender differences in drug effects: implications for anesthesiologists.

BACKGROUND: The gender aspect in pharmacokinetics and pharmacodynamics of anesthetics has attracted little attention. Knowledge of previous work is required to decide if gender-based differences in clinical practice is justified, and to determine the need for research. METHODS: Basis for this paper was obtained by Medline searches using the key words 'human' and 'gender' or 'sex,' combined with individual drug names. The reference lists of these papers were further checked for other relevant studies. RESULTS: Females have 20-30% greater sensitivity to the muscle relaxant effects of vecuronium, pancuronium and rocuronium. When rapid onset of or short duration of action is very important, gender-modified dosing may be considered. Males are more sensitive than females to propofol. It may therefore be necessary to decrease the propofol dose by 30-40% in males compared with females in order to achieve similar recovery times. Females are more sensitive than males to opioid receptor agonists, as shown for morphine as well as for a number of kappa (OP2) receptor agonists. On this basis, males will be expected to require 30-40% higher doses of opioid analgesics than females to achieve similar pain relief. On the other hand, females may experience respiratory depression and other adverse effects more easily if they are given the same doses as males. CONCLUSION: These examples illustrate that gender should be taken into account as a factor that may be predictive for the dosage of several anesthetic drugs. Moreover, there is an obvious need for more research in this area in order to further optimize drug treatment in anesthesia.

Ventricular fibrillation related to reversal of the neuromuscular blockade in a patient with long QT syndrome.

The long QT syndrome (LQTS) is associated with syncopal attacks or even sudden death at a young age due to ventricular fibrillation. We report a patient with an undiagnosed LQTS who had an episode of cardiac arrest during the final part of general anesthesia, immediately after the drugs for reversal of the neuromuscular blockade were given. We suggest that the administration of glycopyrronium might have been the provoking factor in this patient.

Peripheral neurologic deficits in relation to subarachnoid or epidural administration of local anesthetics for surgery. A survey of 21 cases.

BACKGROUND: Recent case reports have suggested that subarachnoid or epidural administration of local anesthetics may cause peripheral neurologic deficits. METHODS: To describe the course and evaluate possible risk factors of such reactions, 21 reports in the Swedish adverse drug reactions register were reviewed. RESULTS: The reports concerned subarachnoid administration of hyperbaric lidocaine (n = 9), plain bupivacaine (n = 4), hyperbaric bupivacaine (n = 2), bupivacaine with epinephrine (n = 1) and mepivacaine (n = 1), and epidural administration of bupivacaine (n = 2) and mepivacaine (n = 2). Pain in the lower extremities was reported in 12 patients (57%) and paresthesias/hypesthesias were reported in 11 patients (52%). Seven reports (33%) concerned low back pain or abdominal pain from Th9-Th10 and downwards. Urinary incontinence was reported in 3 patients, fecal incontinence in 2 patients, and erectile dysfunction, loss of sensation of full bladder and quadriceps muscle paresis were each reported in one patient. Two clinically distinct subgroups of patients were identified, one group with reversible nerve root affection which disappeared within 2 weeks and one group with apparently irreversible nerve root affection, still persistent after 1 month to 4 years. In the group with reversible root symptoms, none had motor deficits, whereas 50% had motor deficits in the group with irreversible symptoms. Possible risk factors include concomitant peripheral neurologic disease and use of other drugs associated with neurotoxicity. CONCLUSIONS: This database study does not contain complete information for the cases reported, and a causal relationship between subarachnoid or epidural administration of local anesthetics and neurologic deficits therefore remains uncertain. The increase in the number of reports on lidocaine after the introduction of very fine-bore spinal needles is consistent with the suspicion that lidocaine at the concentration 50 mg/ml is neurotoxic and that it may not be diluted rapidly enough in the cerebrospinal fluid when injected through such needles.

[Urinary incontinence. A study of occurrence in the municipality of Sund]. / Urininkontinens. En prevalensundersøkelse fra Sund kommune.

The study describes the prevalence and severity of urinary incontinence, factors associated with incontinence, use of remedies and social consequences of incontinence among groups of the population in a small municipality in Western Norway. We sent a 35-item questionnaire by post to all men and women in Sund aged 44-45 and 74-75, total 145 persons. The answers were anonymous, and information was received from 88 persons (61%). 21% of the young males and 50% of the old males were incontinent. The corresponding figures for females were 31% for young and 27% for old females respectively.