losartan-potassium and Craniosynostoses

Pediatric craniosynostosis surgery is associated with significant blood loss often requiring allogenic blood transfusion (ABT). This study explores the clinical effectiveness of preoperative erythropoietin (EPO) administration in pediatric craniosynostosis surgery in reducing transfusion requirements.. A systematic review and meta-analysis of the literature was performed for studies published in English language between 1946 and 2015. Inclusion criteria included original studies in the pediatric population (0-8 years of age) involving preoperative use of EPO in craniofacial procedures with quantitative reporting of perioperative blood transfusion. Extracted data included demographics, hematocrit, hemoglobin, estimated blood loss, number of patients transfused, and amount of ABT.. Four studies met the inclusion criteria with a total of 117 patients. Patients were divided into 2 groups: EPO versus control. No statistical differences were found in the demographics between the 2 groups. Mean preoperative hematocrit level was higher in the EPO group compared with control (43% vs 35%). The percentage of patients who required ABT and the volume of transfused blood were less in the EPO group (54% vs 98% and 84 vs 283 mL, respectively). Meta-analysis of 3 comparable studies showed a lower proportion of patients who needed blood transfusion in the EPO group.. The present meta-analysis demonstrated that preoperative administration of EPO in pediatric craniosynostosis surgery decreased the proportion of patients requiring ABT. In addition, the volume of transfusion was reduced in patients who received EPO. Future randomized studies are needed to establish the cost-effectiveness of routine preoperative EPO administration in craniosynostosis surgery.

Topics: Blood Loss, Surgical; Blood Transfusion; Child; Child, Preschool; Craniosynostoses; Erythropoietin; Hematocrit; Hemoglobins; Humans; Infant; Infant, Newborn; Preoperative Care; Treatment Outcome

Children with craniosynostosis may require cranial vault remodeling to prevent or relieve elevated intracranial pressure and to correct the underlying craniofacial abnormalities. The procedure is typically associated with significant blood loss and high transfusion rates. The risks associated with transfusions are well documented and include transmission of infectious agents, bacterial contamination, acute hemolytic reactions, transfusion-related lung injury, and transfusion-related immune modulation. This study presents the Children's Hospital of Richmond (CHoR) protocol, which was developed to reduce the rate of blood transfusion in infants undergoing primary craniosynostosis repair.. A retrospective chart review of pediatric patients treated between January 2003 and Febuary 2012 was performed. The CHoR protocol was instituted in November 2008, with the following 3 components; 1) the use of preoperative erythropoietin and iron therapy, 2) the use of an intraoperative blood recycling device, and 3) acceptance of a lower level of hemoglobin as a trigger for transfusion (< 7 g/dl). Patients who underwent surgery prior to the protocol implementation served as controls.. A total of 60 children were included in the study, 32 of whom were treated with the CHoR protocol. The control (C) and protocol (P) groups were comparable with respect to patient age (7 vs 8.4 months, p = 0.145). Recombinant erythropoietin effectively raised the mean preoperative hemoglobin level in the P group (12 vs 9.7 g/dl, p < 0.001). Although adoption of more aggressive surgical vault remodeling in 2008 resulted in a higher estimated blood loss (212 vs 114.5 ml, p = 0.004) and length of surgery (4 vs 2.8 hours, p < 0.001), transfusion was performed in significantly fewer cases in the P group (56% vs 96%, p < 0.001). The mean length of stay in the hospital was shorter for the P group (2.6 vs 3.4 days, p < 0.001).. A protocol that includes preoperative administration of recombinant erythropoietin, intraoperative autologous blood recycling, and accepting a lower transfusion trigger significantly decreased transfusion utilization (p < 0.001). A decreased length of stay (p < 0.001) was seen, although the authors did not investigate whether composite transfusion complication reductions led to better outcomes.

Topics: Blood Loss, Surgical; Blood Transfusion; Blood Transfusion, Autologous; Craniosynostoses; Epoetin Alfa; Erythropoietin; Female; Hematinics; Hemoglobins; Humans; Infant; Intraoperative Period; Male; Medical Records; Recombinant Proteins; Retrospective Studies; Sample Size

Surgical correction of craniosynostosis in children is associated with substantial intraoperative bleeding. Tranexamic acid (TXA) decreases intraoperative blood loss during cardiac or orthopedic surgery in children. We hypothesized that intraoperative TXA would reduce blood transfusion relative to placebo in patients pretreated with erythropoietin.. Forty consecutive children, American Society of Anesthesiologists status 1 or 2, scheduled to undergo surgical correction of craniosynostosis were randomly assigned to receive either intravenous TXA or saline, 0.9%, intraoperatively. All children received preoperative erythropoietin (600 U/kg once a week for 3 weeks before surgery). Perioperative blood loss, number and volume of transfusions, percentage of children who underwent transfusion, and side effects were noted after surgery and at the end of the study. Surgeon satisfaction and cost of treatment were also recorded.. There was no significant difference between groups in demographic or surgical data. In the TXA group, the volume of packed erythrocytes transfused was significantly reduced by 85% (from 11 to 1.6 ml/kg) intraoperatively and by 57% (from 16.6 to 7.2 ml/kg) throughout the study period (P < 0.05). Compared with the placebo group, the percentage of children requiring blood transfusion was lower in the TXA group during surgery (9 [45%] of 20 vs. 2 [11%] of 19 children; P < 0.05) and during the whole study period (14 [70%] of 20 vs. 7 [37%] of 19; P < 0.05). Preoperative and postoperative hematologic parameters were comparable in both groups. There were no adverse events.. In children undergoing surgical correction of craniosynostosis and pretreated with erythropoietin, intraoperative TXA reduces the transfusion requirement.

Topics: Adolescent; Antifibrinolytic Agents; Blood Loss, Surgical; Blood Transfusion; Child; Child, Preschool; Craniosynostoses; Double-Blind Method; Erythropoietin; Female; Humans; Intraoperative Care; Male; Tranexamic Acid; Treatment Outcome

Craniosynostotic correction typically performed around infant physiologic nadir of hemoglobin (approximately 3-6 months of age) is associated with high transfusion rates of packed red blood cells and other blood products. As a blood conserving strategy, we studied the use of 1) recombinant human erythropoietin or Procrit (to optimize preoperative hematocrit) and 2) Cell Saver (to recycle the slow, constant ooze of blood during the prolonged case).. UCLA Patients with craniosynostosis from 2003-2005 were divided into 1) the study group (Procrit and Cell Saver) or 2) the control group (n = 79). The study group 1) received recombinant human erythropoietin at 3 weeks, 2 weeks, and 1 week preoperatively and 2) used Cell Saver intraoperatively. Outcomes were based on morbidities and transfusion rate comparisons.. The 2 groups were comparable with regards to age (5.66 and 5.71 months), and operative times (3.11 vs 2.59 hours). In the study group there was a marked increase in preoperative hematocrit (56.2%). The study group had significantly lower transfusions rates (5% vs 100% control group) and lower volumes transfused than in the control group (0.05 pediatric units vs 1.74 pediatric units). Additionally, of the 80% of patients in the study group who received Cell Saver blood at the end of the case, approximately 31% would have needed a transfusion if the recycled blood were unavailable.. Our data showed that for elective craniosynostotic correction, successful blood conserving dual therapy with Procrit and Cell Saver might be used to decrease transfusion rates and the need for any blood products.

Topics: Blood Loss, Surgical; Blood Transfusion; Blood Transfusion, Autologous; Craniosynostoses; Craniotomy; Elective Surgical Procedures; Epoetin Alfa; Erythropoietin; Hematinics; Hematocrit; Hemoglobins; Humans; Infant; Injections, Subcutaneous; Intraoperative Care; Plastic Surgery Procedures; Postoperative Complications; Premedication; Recombinant Proteins; Time Factors; Treatment Outcome

The vast majority of infants and children undergoing craniosynostosis correction receive a blood transfusion. The risks of blood transfusion include, but are not limited to, acute hemolytic reactions (approximately 1 of 250,000), human immunodeficiency virus (approximately 1 of 200,000), hepatitis B and C (approximately 1 of 30,000 each), and transfusion-related lung injuries (approximately 1 of 5000). This prospective, single-blinded, randomized study was undertaken to examine the safety and efficacy of preoperative single weekly dosing with erythropoietin (epoetin alfa) in reducing the rate of transfusion in infants and small children undergoing craniosynostosis repair. A total of 29 patients (<8 years) undergoing craniosynostosis repair were randomized into two groups: one received preoperative erythropoietin (600 U/kg) weekly for 3 weeks, and the other served as a control. All caregivers responsible for blood transfusions were blinded, and strict criteria for transfusion were established. A pediatric hematologist monitored both groups, and all patients received supplemental iron (4 mg/kg). Fourteen patients were randomized to receive erythropoietin, and eight of these 14 patients (57 percent) required transfusion (mean age, 17 months; mean weight, 10.1 kg). Of the six patients not requiring transfusion, three were younger than 12 months old (mean, 6 months). Fourteen of 15 patients (93 percent) in the control group (mean age, 13 months; mean weight, 9.3 kg) required a blood transfusion during the study. The only control patient not requiring transfusion was the eldest (5 years old). The difference between the two groups was statistically significant (Fisher's exact test = 0.03). The control group showed no change in hemoglobin levels from baseline to preoperative levels, but the erythropoietin group increased their average hemoglobin levels from 12.1 to 13.1 g/dl. There were no adverse effects noted among children receiving erythropoietin, nor were there any surgical complications. The authors conclude that the preoperative administration of erythropoietin significantly raised hemoglobin levels and reduced the need for a blood transfusion with craniosynostosis correction. More suggestions are made that may further reduce the need for blood transfusions, and a cost-benefit analysis is discussed.

Topics: Administration, Oral; Blood Loss, Surgical; Blood Transfusion; Child; Child, Preschool; Craniosynostoses; Erythropoietin; Hemoglobins; Humans; Infant; Iron; Preoperative Care; Prospective Studies; Recombinant Proteins; Single-Blind Method

Topics: Blood Transfusion; Child; Craniosynostoses; Erythropoietin; Humans; Preoperative Period; Skull

Assess the effect of a protocol of preoperative erythropoietin (EPO) and ferrous sulfate in addition to perioperative tranexamic acid (TXA) on blood transfusions in patients with coronal or metopic craniosynostosis undergoing cranial vault remodeling (CVR) with fronto-orbital advancement (FOA).. Retrospective review of all coronal and metopic craniosynostosis patients undergoing CVR and FOA from March 2010 to June 2019 was performed. Before 2014 ("Control group"), all patients received blood transfusion at the start of surgery. In 2014, a protocol of preoperative EPO and ferrous sulfate with perioperative TXA and non-automatic transfusion was instituted ("Study group"). Patient demographics and anthropometrics, perioperative hemoglobin (Hb) levels, and transfusion details were collected and compared.. Thirty-six patients met inclusion criteria. Twenty-one patients were in the control group, and 15 in the Study group. Nineteen patients had metopic synostosis, 11 had unicoronal synostosis, and 6 had bicoronal synostosis. There were no significant differences between groups in demographics, operative time, intraoperative crystalloid volume, craniofacial syndromes, or sutures affected. The Study group had higher preoperative Hb (13.9 ± 1.0 vs. 12.6 ± 0.8 g/dL, p < 0.001), lower intraoperative Hb nadir (7.4 ± 1.8 vs. 9.2 ± 1.2 g/dL) lower intraoperative transfusion rate (66.7% vs. 100%, p = 0.008), lower postoperative transfusion rate (0% vs 28.6%, p = 0.03), and exposure to fewer unique units of packed red blood cells (0.7 ± 0.6 vs. 1.5 ± 0.9 units).. Our protocol resulted in decreased transfusion needs. These results add valuable information to the growing body of work on transfusion reduction in craniosynostosis surgery.

Topics: Blood Loss, Surgical; Blood Transfusion; Craniosynostoses; Erythropoietin; Humans; Infant; Retrospective Studies; Tranexamic Acid

Approximately one in 2000 babies are born with craniosynostosis, and primary open repair is typically performed before 1 year of age. Historically, the procedure has been associated with nearly 100 percent transfusion rates. To decrease the rates of transfusion, the authors' center has developed a novel multimodal blood conservation protocol.. The authors administered their standard of care to children aged 1 year or younger undergoing primary repair of craniosynostosis between 2008 and 2014. In 2014, the authors implemented the following protocol: (1) preoperative erythropoietin and ferrous sulfate, (2) local anesthetic with epinephrine infiltration of the incision, (3) PlasmaBlade incision and subgaleal dissection, (4) hypervolemic hemodilution, and (5) intravenous tranexamic acid. Procedures performed before the protocol implementation served as controls. The authors performed classic fronto-orbital advancement with anterior cranial vault remodeling for coronal and metopic craniosynostosis. For lambdoid and sagittal craniosynostosis, barrel stave osteotomies, cranial base outfracture, and interposition bone grafting were performed.. A total of 279 children with a mean age of 6 months who had craniosynostosis repairs were included. One hundred forty-five underwent repair before the authors' protocol, and 134 had repairs during the authors' blood conservation protocol. Both groups were similar in demographics. Overall blood loss and operative times were significantly reduced by 73 percent and 11 percent, respectively. Blood transfusion rate decreased 92 percent (p < 0.001).. These results show a strong association between the authors' blood conservation protocol and significantly reduced transfusion rates. The authors believe this is a significant step forward and can be safely applied in the great majority of children undergoing craniosynostosis repairs.. Therapeutic, III.

Topics: Blood Loss, Surgical; Craniosynostoses; Dissection; Epinephrine; Erythropoietin; Female; Ferrous Compounds; Hemodilution; Humans; Infant; Infant, Newborn; Male; Osteotomy; Plastic Surgery Procedures; Vasoconstrictor Agents

To assess the success of a protocol using preoperative erythropoietin (EPO) and iron with perioperative tranexamic acid (TXA) in reducing blood transfusion in sagittal craniosynostosis surgery.. A retrospective chart review of all sagittal craniosynostosis patients undergoing open repair at our institution since 2010 was conducted. A novel protocol of preoperative EPO with iron and perioperative TXA, along with a shift away from automatic transfusion, was initiated in 2014. Perioperative hemoglobin levels, length of stay, and transfusion rates were compared between the historical control and the study group receiving the protocol.. A total of 36 patients met inclusion criteria. Twenty-eight patients were male and 8 were female. Twenty-two patients were in the control group receiving neither TXA nor EPO and automatically received a transfusion, while 14 were in the study group and received the full protocol. There were no significant demographic differences between groups. Within the control group, 100% of patients were transfused compared with 14.3% of the study group (p < 0.0001). The study group also had a shorter postoperative length of stay in the hospital (mean, 3.4 days; range, 3-6) than the control (mean, 4 days; range, 2-5.5, p = 0.038). The study group had a higher preoperative hemoglobin than the control (13.6 vs. 11.8 g/dL, p = 0.0001).. Our protocol of preoperative EPO and iron with perioperative TXA increased the preoperative hemoglobin and was associated with a low transfusion rate without negatively impacting postoperative course.

Topics: Antifibrinolytic Agents; Blood Loss, Surgical; Blood Transfusion; Child; Clinical Protocols; Craniosynostoses; Erythropoietin; Female; Hemoglobins; Hospitals, Pediatric; Humans; Iron; Male; Minnesota; Plastic Surgery Procedures; Retrospective Studies; Tranexamic Acid

Topics: Blood Gas Analysis; Blood Loss, Surgical; Blood Substitutes; Blood Transfusion, Autologous; Child; Craniosynostoses; Erythropoietin; Hemodilution; Humans; Intraoperative Care; Lactic Acid; Monitoring, Intraoperative

A retrospective study was performed to evaluate whether pretreatment with erythropoietin and iron combined with acute preoperative normovolaemic haemodilution (APNH) could decrease homologous blood transfusion in craniosynostosis (CS) surgery. A treated group was compared with a historical group of infants who underwent surgery with no pretreatment.. The charts of 25 healthy infants who underwent CS surgery were reviewed. Nine of them underwent surgery with no treatment beforehand. Sixteen infants were given erythropoietin at a dosage of 300 U.kg -1 two times per week and iron (elemental iron 10 mg.kg-1.day-1) for 3 weeks before surgery. On the day of surgery APNH was performed after induction of general anaesthesia; a precalculated amount of autologous blood was withdrawn and replaced by hydroxyethyl starch 6%.. Eleven of the 16 infants of the study group received only autologous blood. Five of 16 received homologous blood transfusion vs seven of nine infants in the control group.. APNH combined with erythropoietin was effective in reducing homologous blood requirements during CS surgery. Further studies are necessary on a larger scale to assess the role of this technique in avoiding homologous blood transfusion and to evaluate how infants can benefit from this combined approach.

Topics: Anesthesia; Blood Transfusion; Craniosynostoses; Erythropoietin; Female; Hematocrit; Hemodilution; Humans; Hydroxyethyl Starch Derivatives; Infant; Male; Plasma Substitutes; Preoperative Care; Recombinant Proteins; Retrospective Studies

Topics: Blood Loss, Surgical; Blood Transfusion; Child; Child, Preschool; Craniosynostoses; Erythropoietin; Hemoglobinometry; Humans; Infant; Randomized Controlled Trials as Topic; Recombinant Proteins

Two siblings were identified with severe hypoproliferative microcytic anemia and iron malabsorption, in the absence of any gastrointestinal disorder or blood loss. These children had severe microcytosis (MCV 48 fl, hemoglobin 7.5 g/dl) with decreased serum iron, elevated serum TIBC, and decreased serum ferritin, despite prolonged treatment with oral iron. An iron challenge study with an oral dose of 2 mg/kg elemental iron as ferrous sulfate documented iron malabsorption. After treatment with intravenous iron dextran, there was an absence of the expected reticulocytosis and only a partial correction of the hemoglobin, hematocrit, and microcytosis. The bone marrow was hypocellular with abnormal iron incorporation into erythroid precursor cells. This appears to be a rare form of inherited anemia characterized by iron malabsorption and disordered iron metabolism that only partially corrects after the administration of parenteral iron. These features resemble those found in the microcytic mouse (mk/mk), which also has severe microcytic anemia and iron malabsorption that partially responds to parenteral iron.

Topics: Administration, Oral; Anemia, Iron-Deficiency; Animals; Biological Transport; Bone Marrow; Cell Compartmentation; Cell Size; Child; Child, Preschool; Colony-Forming Units Assay; Craniosynostoses; Drug Resistance; Erythrocytes, Abnormal; Erythroid Precursor Cells; Erythropoietin; Female; Ferrous Compounds; Humans; Infusions, Intravenous; Intestinal Absorption; Intracellular Fluid; Iron; Iron-Dextran Complex; Malabsorption Syndromes; Male; Mice; Mice, Mutant Strains