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Background@#Appropriate blood component transfusion might differ between intraoperative massive bleeding and traumatic massive bleeding in the emergency department because trauma patients initially bleed undiluted blood and replacement typically lags behind blood loss. We compared these two blood loss scenarios, intraoperative and traumatic, using a computer simulation. @*Methods@#We modified the multi-compartment dynamic model developed by Hirshberg and implemented it using STELLA 9.0. In this model, blood pressure changes as blood volume fluctuates as bleeding rate and transcapillary refill rate are controlled by blood pressure. Using this simulation, we compared the intraoperative bleeding scenario with the traumatic bleeding scenario. In both scenarios, patients started to bleed at a rate of 50 ml/min. In the intraoperative bleeding scenario, fluid was administered to maintain isovolemic status; however, in the traumatic bleeding scenario, no fluid was supplied for up to 30 min and no blood was supplied for up to 50 min. Each unit of packed red blood cells (PRBC) was given when the hematocrit decreased to 27%, fresh frozen plasma (FFP) was transfused when plasma was diluted to 30%, and platelet concentrate (PC) was transfused when platelet count became 50,000/ml. @*Results@#In both scenarios, the appropriate ratio of PRBC:FFP was 1:0.47 before PC transfusion, and the ratio of PRBC:FFP:platelets was 1:0.35:0.39 after initiation of PC transfusion. @*Conclusion@#The ratio of transfused blood component did not differ between the intraoperative bleeding and traumatic bleeding scenarios.
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PURPOSE: Acute normovolemic hemodilution (ANH) is an autologous transfusion method, using blood collected during surgery, to reduce the need for allogeneic blood transfusion. ANH is controversial because it may lead to various complications. Among the possible complications, anastomotic leakage is one that would have a significant effect on the operation outcome. However, the relationship between ANH and anastomotic site healing requires additional research. Therefore, we conducted this prospective study of ANH, comparing it with standard intraoperative management, undergoing gastric anastomosis in rats. METHODS: Sixteen Sprague-Dawley rats were randomly assigned to three groups: group A, surgery with ANH; group N, surgery with standard intraoperative management; and group C, sham surgery with standard intraoperative management. ANH was performed in group A animals by, removing 5.8–6.6 mL of blood and replacing it with 3 times as much crystalloid. All rats were enthanized on postoperative day 6, and histopathologic analyses were performed. RESULTS: The mean hematocrit values, after hemodilution were 22.0% (range, 18.0%–29.0%), group A; 33.0% (29.0%–35.0%), group N; and 32.5% (29.0%–34.0%), group C. There were significant differences between groups A and N (P = 0.019, P = 0.009, P = 0.004, P = 0.039, and P = 0.027), and between groups N and C (P = 0.006, P = 0.027, P = 0.04, P = 0.008, and P = 0.009) with respect to inflammatory cell numbers, neovascularization, fibroblast numbers, edema and necrosis, respectively; there were no differences between groups A and N. CONCLUSION: In rat model, anastomotic complications did not increase in the ANH group, compared with the standard intraoperative management group.
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Animais , Ratos , Fístula Anastomótica , Transfusão de Sangue , Contagem de Células , Edema , Fibroblastos , Hematócrito , Hemodiluição , Métodos , Modelos Animais , Necrose , Estudos Prospectivos , Ratos Sprague-DawleyRESUMO
BACKGROUND: A growing body of evidence suggests that neuroinflammation, which is characterized by infiltration of immune cells, activation of mast cells and glial cells, and production of inflammatory mediators in the peripheral and central nervous systems, plays an important role in the induction and maintenance of chronic pain. Palmitoylethanolamide (PEA), which is a type of N-acylethanolamide and a lipid, has an anti-inflammatory effect. Relative to the anti-inflammatory effect, little is known about its analgesic effect in chronic pain. This study aimed to determine whether PEA relieves chronic inflammatory and neuropathic pain. METHODS: Male Sprague-Dawley rats were injured by transection of the left L5 and L6 spinal nerves to induce neuropathic pain or were injected with monoiodoacetic acid into the synovial cavity of knee joints to induce inflammatory pain. To assess the degree of pain, two kinds of stimuli - pressing von Frey filaments and wetting with acetone - were applied to the plantar surface of the rat to measure mechanical and cold sensitivity, respectively. Pain was measured by assessing behavioral responses, including paw withdrawal response threshold and paw withdrawal frequency upon stimulation. RESULTS: Neuropathic pain caused by spinal nerve transection (SNT) decreased the mechanical threshold and increased the frequency of response to acetone application. But, cold allodynia caused by SNT did not decrease the withdrawal frequency. Mechanical hyperalgesia caused by chronic inflammation was significantly reduced by both intraperitoneal and intra-articular injections of PEA. CONCLUSIONS: These outcomes revealed that PEA might be effective in relieving inflammatory and neuropathic pain, especially pain induced by mechanical hyperalgesia, but not cold allodynia.
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Animais , Humanos , Masculino , Ratos , Acetona , Sistema Nervoso Central , Dor Crônica , Hiperalgesia , Inflamação , Injeções Intra-Articulares , Ácido Iodoacético , Articulação do Joelho , Mastócitos , Neuralgia , Neuroglia , Pisum sativum , Ratos Sprague-Dawley , Nervos EspinhaisRESUMO
Postoperative visual loss (POVL) after non-ophthalmic surgery is rare, with a reported incidence ranging from 0.013 to 0.2%. Most perioperative visual loss is associated with spine operations and cardiac bypass procedures. The most common cause of POVL is ischemic optic neuropathy. However, there are no previous reports of postoperative visual loss after laparoscopic appendectomy. A 43-year-old female with no underlying disease underwent laparoscopic appendectomy; the operation was completed in one hour and her blood pressure was stable during the perioperative period. In the post-anesthetic care unit, the patient complained of nausea and headache, but she did not complain of any unusual visual symptoms. Approximately one hour after arriving at the ward, the patient complained of visual disturbance. Neurologic examination revealed left homonymous hemianopsia, and subarachnoid hemorrhage and intracerebral hemorrhage were found in the occipital area on brain MRI.
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Adulto , Feminino , Humanos , Apendicectomia , Pressão Sanguínea , Encéfalo , Hemorragia Cerebral , Cefaleia , Hemianopsia , Incidência , Imageamento por Ressonância Magnética , Náusea , Exame Neurológico , Neuropatia Óptica Isquêmica , Período Perioperatório , Coluna Vertebral , Hemorragia SubaracnóideaRESUMO
No abstract available.
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Humanos , Hipóxia , Artrite Reumatoide , Intubação , Edema PulmonarRESUMO
Aspiration pneumonitis is best defined as an acute lung injury, following the aspiration of regurgitated gastric contents. Major cause of pulmonary aspiration, during anesthesia, is gastric contents. Pulmonary aspiration can present symptoms of wheezing, coughing, dyspnea, cyanosis, pulmonary edema, hypotension, and hypoxemia, which may progress rapidly to severe acute respiratory distress syndrome (ARDS). However, there was no report of massive alveolar hemorrhage associated with aspiration pneumonitis. A 63-year-old man, who had undergone a total gastrectomy and received adjuvant chemotherapy, four months ago, was scheduled for adhesiolysis of the small bowel. The patient occurred aspiration of gastric contents, during induction of anesthesia, and subsequently, hypoxia developed during surgery. The patient moved to an intensive care unit (ICU), without extubation. Mechanical ventilation with PEEP was performed in an ICU. However, the patient died by ARDS and massive alveolar hemorrhage.
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Humanos , Pessoa de Meia-Idade , Lesão Pulmonar Aguda , Adesivos , Anestesia , Hipóxia , Quimioterapia Adjuvante , Tosse , Cianose , Dispneia , Gastrectomia , Hemorragia , Hipotensão , Unidades de Terapia Intensiva , Pneumonia , Edema Pulmonar , Respiração Artificial , Síndrome do Desconforto Respiratório , Sons RespiratóriosRESUMO
BACKGROUND: Wake-up tests may be necessary during surgery for kypho-scoliosis to ensure that spinal function remains intact. It is difficult to predict the time when patients can respond to a verbal command. We evaluated the effectiveness of the bispectral index (BIS) and its relation to patients' levels of consciousness in wake-up tests during desflurane and sevoflurane anesthesia. METHODS: Eighteen patients each were enrolled in the desflurane and sevoflurane groups for spinal correction surgery. We measured BIS values, blood pressure, heart rate, and consciousness state and time, at the points when patients responded during the wake-up test. RESULTS: The BIS values when patients made fists upon a verbal command (T3) were 86.7 +/- 7.5 for desflurane and 90.3 +/- 5.4 for sevoflurane. Patients in the desflurane group had significantly shorter wake up delays than those in the sevoflurane group (6.9 +/- 1.8 min vs. 11.8 +/- 3.6 min). However, there was no difference between the groups in the time between the response to a verbal command and the time when a patient moved their toes in response to verbal commands. No recall of the wake-up tests occurred in either group. CONCLUSIONS: The values obtained using the BIS index could to some extent predict the time of a patient's and would be informative during desflurane and sevoflurane anesthesia. Moreover, desflurane permitted faster responses to verbal commands than sevoflurane, and allowed the wake-up test to be performed sooner.
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Humanos , Anestesia , Pressão Sanguínea , Estado de Consciência , Sacarose Alimentar , Frequência Cardíaca , Isoflurano , Éteres Metílicos , Dedos do PéRESUMO
Transfusion-related acute lung injury (TRALI) is a serious complication following the transfusion of blood products. TRALI is under-diagnosed and under-reported because of a lack of awareness. TRALI occurs within 6 hours of transfusion in the majority of cases and its presentation is similar to other forms of acute lung injury. We report on the case of a 34-year-old pregnant woman who suffered from TRALI after transfusion during Cesarean section.
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Adulto , Feminino , Humanos , Gravidez , Lesão Pulmonar Aguda , Transfusão de Sangue , Cesárea , GestantesRESUMO
BACKGROUND: We studied the hemodynamic changes induced by pneumoperitoneum and a reversed Trendelenburg in elderly patients with increased cardiac risk (ASA class III; n = 30; age 70.8 +/- 4.9 years, mean +/- SD) and compared the results with elderly patients at normal risk (ASA class II; n = 30; age 69.2 +/- 4.1 years) during laparoscopic cholecystectomy. METHODS: The transesophageal Doppler monitor was performed after induction of general anesthesia (pre-incision), after onset of pneumoperitoneum (insufflation), after head-up (20degrees) and a left lateral tilt (15degrees) (reversed Trendelenburg) and after deflation and horizontal position (desufflation). Mean arterial pressure (MAP), heart rate, cardiac index (CI) and systemic vascular resistance (SVR) were measured, respectively. RESULTS: Induction of pneumoperitoneum and head-up tilt in patients with cardiac risk resulted significantly in a decrease in CI and an increase in SVR compared with patients with normal risk (P < 0.05), and that remained until deflation, but no interval changes in MAP and heart rate. The CI, MAP and heart rate decreased and SVR increased significantly in patients with cardiac risk compared with patients with normal risk before incision (P < 0.05). No complications occurred. The results indicate that pneumoperitoneum and a reversed Trendelenburg are associated with significant but relatively benign hemodynamic changes. CONCLUSIONS: Anesthesia for laparoscopic cholecystectomy in elderly patients with increased cardiac risk should be performed with an adequate hemodynamic monitoring.
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Idoso , Humanos , Anestesia , Anestesia Geral , Pressão Arterial , Colecistectomia Laparoscópica , Cardiopatias , Frequência Cardíaca , Hemodinâmica , Compostos Organotiofosforados , Pneumoperitônio , Resistência VascularRESUMO
Esmolol is a cardioselective beta-blocker with a very rapid onset of action and a short half-life. Labetalol is a combined alpha- and beta-adrenoceptor blocking agent. It is a nonselective antagonist at beta-adrenoceptors and a competitive antagonist of postsynaptic alpha 1-adrenoceptors. A 51 year old female patient was transferred to the operating room for performing spinal fusion under general anesthesia. She had no operation and medication history. The initial heart rate was 150 beats/min. Despite administering several bolus injections of esmolol, the heart rate was not decreased to under 130 beats/min. But the heart rate was decreased to 100 beats/min after the administration of labetalol 5 mg and this rate was maintained without an additional injection. The vital signs were stable until the operation was finished and the patient recovered uneventfully in the recovery room. The postoperative laboratory findings revealed that she had hyperthyroidism. We report here on an anesthetic experience of effective labetalol treatment for esmolol-resistant tachycardia in a patient who was under general anesthesia.
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Feminino , Humanos , Anestesia Geral , Meia-Vida , Frequência Cardíaca , Hipertireoidismo , Labetalol , Salas Cirúrgicas , Propanolaminas , Sala de Recuperação , Fusão Vertebral , Taquicardia , Sinais VitaisRESUMO
BACKGROUND: This study was conducted to compare the effects of remifentanil, lidocaine, nicardipine and nitroglycerin used in conjunction with thiopental-sevoflurane on hemodynamic changes induced by direct laryngoscopy and tracheal intubation. METHODS: Seventy-five ASA class I or II patients scheduled for elective surgery were randomly divided into 5 groups. After induction of anesthesia with thiopental, sevoflurane and rocuronium, they were administered an intravenous bolus of either saline (Group S), remifentanil 1microgram/kg (Group R), lidocaine 1.5 mg/kg (Group L), nicardipine 20microgram/kg (Group N) or nitroglycerin 2microgram/kg (Group G). Tracheal intubation was then conducted 90 seconds after the drug was administered. The systolic blood pressure, diastolic blood pressure and heart rate were measured prior to the administration of anesthesia, before intubation, at 1 min after intubation and at 3 min after intubation for each patient. RESULTS: The systolic blood pressure, diastolic blood pressure and heart rate at 1 min after intubation were significantly lower in Group R than in Group S. In addition, the systolic blood pressure and diastolic blood pressure prior to intubation were significantly lower in Group N than in Group S. CONCLUSIONS: Remifentanil 1microgram/kg was most effective at controlling hemodynamic changes induced by direct laryngoscopy and tracheal intubation when compared with lidocaine, nicardipine and nitroglycerin.
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Humanos , Androstanóis , Anestesia , Pressão Sanguínea , Frequência Cardíaca , Hemodinâmica , Intubação , Laringoscopia , Lidocaína , Éteres Metílicos , Nicardipino , Nitroglicerina , Piperidinas , TiopentalRESUMO
BACKGROUND: We performed a prospective, randomized, and controlled trial to evaluate the effect of an intravenous fentanyl and propofol on the variation in BIS level associated tracheal suction. METHODS: Thirty ICU patients intubated or tracheostomized were randomly allocated to control and experimental groups. Control group was received saline and experimental groups were received propofol with or without fentanyl intravenously prior to tracheal suction. And then we monitored BIS index, blood pressure, heart rate and SpO2 before, during and after tracheal suction. RESULTS: BIS index was significantly lower in propofol plus fentanyl group than others during experiment (P < 0.05). Heart rate and blood pressure in propofol plus fentanyl group also less increased than those in control or propofol group during tracheal suction (P < 0.05). CONCLUSIONS: These results suggest that co-administration of propofol and fentanyl has more effective than propofol alone in sedation and analgesia of ICU patients during tracheal suction.
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Humanos , Analgesia , Pressão Sanguínea , Fentanila , Frequência Cardíaca , Propofol , Estudos Prospectivos , SucçãoRESUMO
BACKGROUND: The hemodynamic and metabolic effects of tourniquet application undergoing knee surgery with general anesthesia in elderly patients with hypertension have been rarely reported. We evaluated the hemodynamic and metabolic effects in elderly patients compared with young adults. METHODS: Thirty elderly patients (elderly hypertension group, 71.8 +/- 3.9 years) with chronic hypertension undergoing total knee replacement and 30 young adults (normal group, 33.1 +/- 5.1 years) undergoing knee surgery were studied. Mean arterial pressure (MAP), heart rate, cardiac index (CI) by esophageal doppler method, and systemic vascular resistance index (SVRI) were measured before, during, and after tourniquet application. pH, PaO2, PaCO2, Hb and lactate blood concentrations were also measured. RESULTS: MAP increased 25% and 16% in elderly hypertension and normal groups during inflation, respectively (P < 0.05) and returned to basal values after deflation. CI increased to 30% higher than basal values in both groups after deflation (P < 0.05). SVRI decreased 31% and 19% in elderly hypertension and normal groups after deflation, respectively (P < 0.05). After deflation, PaCO2 and lactate increased (P < 0.05). CONCLUSIONS: Elderly patients with hypertension have the significant hemodynamic changes during and after tourniquet application than before, however, there are no differences compared to normal group. These elderly patients should be needed the active hemodynamic monitoring due to the lower compensatory ability.
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Idoso , Humanos , Adulto Jovem , Anestesia Geral , Pressão Arterial , Artroplastia do Joelho , Frequência Cardíaca , Hemodinâmica , Concentração de Íons de Hidrogênio , Hipertensão , Inflação , Joelho , Ácido Láctico , Torniquetes , Resistência VascularRESUMO
Severe hypoxemia is considered by many to contraindicate major surgery. Several studies have shown that dependency on oxygen, PaO2 or = 45 mmHg, FEV1 < or = 50%, and FVC < or = 75% are indicative of a high risk of morbidity and mortality following major surgical procedures. Here, we report our experience of the use of regional anesthesia in such patients. One patient was a 82-year-old female patient who was scheduled for partial hip replacement due to a fracture of the right femur. Her pulmonary function test and preoperative arterial blood gas analysis results were as follows: FVC 1.23 L (49.1%), FEV1 1.11 L (61.3%), FEV1/FVC 90.2%, a room air pH 7.423, PaCO2 43.0 mmHg, PaO2 46.4 mmHg, SaO2 84.5% and base excess 2.7 mM/L. Another patient was a 79-year-old COPD male patient scheduled for appendectomy. His immediate preoperative arterial blood gas analysis results were; room air pH 7.368, PaCO2 62.1 mmHg, PaO2 43.8 mmHg, SaO2 77.4% and base excess 7.3 mM/L. Both patients underwent and tolerated surgery safely with regional anesthesia. No permanent sequela occured postoperatively in these cases. No severe changes in room air arterial blood gas levels were observed before and after surgery. We present a review of two cases of severe hypoxemia in which a regional block was used.
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Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Anestesia por Condução , Anestesia Epidural , Raquianestesia , Hipóxia , Apendicectomia , Gasometria , Fêmur , Quadril , Concentração de Íons de Hidrogênio , Mortalidade , Oxigênio , Doença Pulmonar Obstrutiva Crônica , Testes de Função RespiratóriaRESUMO
BACKGROUND: Hemodilution is known to increase cerebral blood flow, but it is not known why it is. We tried to investigate about these question like above. METHODS: Blood flow were checked on carotid artery after hemodilution by using electromagnetic blood flow-meter in 10 rabbits. Hemodilution was induced as 15 ml of lactated Ringers solution (LR) was infused after removing 5 ml of blood. Hemodilution was done 5 times in each rabbit. At 15 minutes after each hemodilution procedure, blood flow was checked and arterial blood gas analysis, and they compared with control data. The Sigma STAT and one way repeated measured ANOVA in Bonfferoni correction and regression analysis with DBSTAT PC application were used for statical analysis. RESULTS: Hemoglobin concentration and hematocrit in blood according to each hemodilution step decreased. At the same time, carotid blood flow increased following hemodilution. Though PaO2 level was not changed, CaO2 and pH, bicarbonate, and base excess in accordance with hemodilution were decreased. Also carotid blood flow calculated as increase 2.5 ml/min whenever hematocrit decreased 1%. CONCLUSIONS: We concluded as follow. Carotid blood flow increased to 2.5 ml/min (4.7%) whenever hematocrit decreased 1% by hemodilution. Whenever 15 ml of L/R solution was infused for acute hemodilution, carotid blood flow increased, on the contrary, hematocrit and arterial oxygen content decreased. Metabolic acidosis was induced by the large amount of L/R solution and it may be affected to carotid blood flows.
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Coelhos , Equilíbrio Ácido-Base , Acidose , Gasometria , Artérias Carótidas , Hematócrito , Hemodiluição , Concentração de Íons de Hidrogênio , Imãs , OxigênioRESUMO
Laryngeal cysts, including epiglottic cysts, are rare lesions which are clinically asymptomatic in many cases. Rarely laryngeal cysts cause unexpected airway management difficultties perioperatively. We report up on a case of laryngeal cyst that caused postextubation airway obstruction and negative-pressure pulmonary edema. A 25-year-old man was admitted for brain surgery with neurofibromatosis. He did not have any specific airway problem preoperatively, and anesthesia was done uneventfully. But when he was extubated after surgery, he revealed symptoms of upper airway obstruction in the recovery room. We reintubated him easily, and then we found a laryngeal cyst. Though negative-pressure pulmonary edema occurred after reintubation, he responded to conservative treatment and was discharged without specific problems. We present a review of postextubation airway obstruction and negative-pressure pulmonary edema due to a laryngeal cyst.
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Adulto , Humanos , Manuseio das Vias Aéreas , Obstrução das Vias Respiratórias , Anestesia , Encéfalo , Neurofibromatoses , Edema Pulmonar , Sala de RecuperaçãoRESUMO
BACKGROUND: It is difficult to treat tourniquet-induced hypertension despite adequate anesthesia, and the mechanism of that is not known. And it may be possible that intraoperative continuous infusion of opioid induces preemptive analgesia postoperatively. We investigated the effect of intraoperative continuous i.v. fentanyl on tourniquet induced cardiovascular changes and postoperative preemptive analgesia in total knee replacements. METHODS: Sixty patients were randomly assigned to two groups; In study group (1.5microgram/kg loading and 0.5microgram/kg/hr continuous infusion of fentanyl before skin incision and tourniquet inflation) and control group (no treatment). Anesthesia was maintained with enflurane (1-2 MAC) and 50% nitrous oxide in oxygen. Arterial pressure and heart rate were compared between two groups. They received postoperative pain treatment with patient-controlled analgesia (PCA) with fentanyl during the postoperative 48 hours after total knee replacement. Visual analog scale (VAS) scores at either rest or movement were used to assess pain. Total fentanyl dose delivered, number of PCA requests, supplemental analgesics, overall satisfaction score and adverse events were evaluated. RESULTS: There were no significant differences between the two groups on cardiovascular changes by tourniquet induced pain effect. VAS, PCA delivered dose and PCA demands at movement in the 24-48 hour decreased in study group compared with control group (P < 0.05). But there were no significant differences between the two groups on the other time periods except 24-48 hour's patient satisfaction and adverse events. CONCLUSIONS: We suggest that intraoperative continuous i.v. fentanyl infusion dose not affect cardiovascular change by tourniquet induced pain. But it may induce preemptive analgesia postoperatively.
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Humanos , Analgesia , Analgesia Controlada pelo Paciente , Analgésicos , Anestesia , Pressão Arterial , Artroplastia do Joelho , Enflurano , Fentanila , Frequência Cardíaca , Hipertensão , Óxido Nitroso , Oxigênio , Dor Pós-Operatória , Anafilaxia Cutânea Passiva , Satisfação do Paciente , Pele , Torniquetes , Escala Visual AnalógicaRESUMO
A 22 year old male with hemophilia B was scheduled for the correction of a right subtrochanteric femur fracture. Plasma concentration of coagulation factor IX in this patient was 50% of the normal level and the partial thromboplastin time was 57 seconds on the first day of hospital administration. We started the intravenous administration of facnyne injection (factor IX) 11 days before the operation when his plasma concentration was 20%. His plasma concentration was 40% on the operation day. The operation and general anesthesia were accomplished safely without severe hemorrhage or major complication. He received facnyne injection continuously until the 5th postoperative day: 25-43% of his plasma concentrations of factor IX was maintained. He had no problem with postoperative care.
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Humanos , Masculino , Adulto Jovem , Administração Intravenosa , Anestesia Geral , Fator IX , Fêmur , Hemofilia A , Hemofilia B , Hemorragia , Administração Hospitalar , Tempo de Tromboplastina Parcial , Plasma , Cuidados Pós-OperatóriosRESUMO
Pulmonary embolism is a common medical complication following major orthopedic procedures of the lower extremities and a leading cause of morbidity and mortality. However, the clinical manifestations of pulmonary embolism are nonspecific and it may be difficult to diagnose. An 82 years old female with severe restrictive pulmonary disease received the elective operation for the fracture of left femur neck under combined spinal-epidural anesthesia. During the operation, we sometimes gave her oxygen via face mask and maintained oxygen saturation of more than 80% which was measured by a pulse oxymeter. The operation and anesthesia was performed uneventfully. On the seventh postoperative day, she showed tachycardia suddenly and cardiac arrest later on the electrocardiogram. After cardiopulmonary resuscitation, she was transferred to intensive care unit and checked by a computed tomography and echocardiography. She was diagnosed with pulmonary embolism and deep vein thrombosis and treated with heparin and urokinase. But she did not improve and died.