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1.
Hydroxyurea for secondary stroke prevention in children with sickle cell anaemia: a systematic review of clinical evidence and outcomes
Aderinto, N., Olatunji, G., Kokori, E., Abdulbasit, M.
Annals of medicine and surgery (2012). 2024;86(2):1042-1047
Abstract
BACKGROUND Stroke remains one of the leading complications of sickle cell anaemia (SCA) in children. Traditionally, SCA treatment focused on symptom relief. However, the high incidence of strokes in children has prompted a reevaluation of treatment, particularly hydroxyurea, for secondary stroke prevention. This study assesses hydroxyurea's effectiveness and safety in preventing secondary strokes in paediatric SCA patients. METHODS This systematic review followed a pre-defined protocol registered with PROSPERO. Comprehensive searches were conducted across PubMed, Embase, Scopus, MEDLINE, Google Scholar, and the Cochrane Library up to August 2023. Studies were included involving paediatric SCA patients at risk of secondary stroke, assessing hydroxyurea as the primary intervention. RESULTS A total of six studies meeting inclusion criteria were included. The effectiveness of hydroxyurea in preventing secondary strokes, with variable responses reported across studies. Adverse effects, including mild neutropenia, are associated with hydroxyurea treatment but with variability in reported toxicity levels. CONCLUSION Hydroxyurea holds promise in preventing recurrent strokes in children with SCA, though its efficacy and safety profiles vary among individuals. Optimal dosages and treatment durations require further investigation, necessitating vigilant monitoring of haematological parameters. Future research should refine dosing strategies, consider individual patient characteristics, assess long-term effects, and explore ancillary benefits beyond stroke prevention.
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Desmopressin to reduce periprocedural bleeding and transfusion: a systematic review and meta-analysis
Wang, C., Lebedeva, V., Yang, J., Anih, J., Park, L. J., Paczkowski, F., Roshanov, P. S.
Perioperative medicine (London, England). 2024;13(1):5
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Abstract
We systematically reviewed the literature to investigate the effects of peri-procedural desmopressin in patients without known inherited bleeding disorders undergoing surgery or other invasive procedures. We included 63 randomized trials (4163 participants) published up to February 1, 2023. Seven trials were published after a 2017 Cochrane systematic review on this topic. There were 38 trials in cardiac surgery, 22 in noncardiac surgery, and 3 in non-surgical procedures. Meta-analyses demonstrated that desmopressin likely does not reduce the risk of receiving a red blood cell transfusion (25 trials, risk ratio [RR] 0.95, 95% confidence interval [CI] 0.86 to 1.05) and may not reduce the risk of reoperation due to bleeding (22 trials, RR 0.75, 95% CI 0.47 to 1.19) when compared to placebo or usual care. However, we demonstrated significant reductions in number of units of red blood cells transfused (25 trials, mean difference -0.55 units, 95% CI - 0.94 to - 0.15), total volume of blood loss (33 trials, standardized mean difference - 0.40 standard deviations; 95% CI - 0.56 to - 0.23), and the risk of bleeding events (2 trials, RR 0.45, 95% CI 0.24 to 0.84). The certainty of evidence of these findings was generally low. Desmopressin increased the risk of clinically significant hypotension that required intervention (19 trials, RR 2.15, 95% CI 1.36 to 3.41). Limited evidence suggests that tranexamic acid is more effective than desmopressin in reducing transfusion risk (3 trials, RR 2.38 favoring tranexamic acid, 95% CI 1.06 to 5.39) and total volume of blood loss (3 trials, mean difference 391.7 mL favoring tranexamic acid, 95% CI - 93.3 to 876.7 mL). No trials directly informed the safety and hemostatic efficacy of desmopressin in advanced kidney disease. In conclusion, desmopressin likely reduces periprocedural blood loss and the number of units of blood transfused in small trials with methodologic limitations. However, the risk of hypotension needs to be mitigated. Large trials should evaluate desmopressin alongside tranexamic acid and enroll patients with advanced kidney disease.
PICO Summary
Population
Children or adults without known inherited bleeding disorders undergoing surgery or other invasive procedures (63 randomised controlled trials, n= 4,163).
Intervention
Desmopressin administered intravenously or subcutaneously before, during, or immediately after a surgical or interventional procedure.
Comparison
Placebo, usual care, or antifibrinolytic agents.
Outcome
Meta-analyses demonstrated that desmopressin likely does not reduce the risk of receiving a red blood cell transfusion (25 trials, risk ratio [RR] 0.95; 95% confidence interval (CI) [0.86, 1.05]) and may not reduce the risk of reoperation due to bleeding (22 trials, RR 0.75; 95% CI [0.47, 1.19]) when compared to placebo or usual care. However, the authors demonstrated significant reductions in number of units of red blood cells transfused (25 trials, mean difference -0.55 units; 95% CI [-0.94, -0.15]), total volume of blood loss (33 trials, standardized mean difference - 0.40 standard deviations; 95% CI [-0.56, -0.23]), and the risk of bleeding events (2 trials, RR 0.45; 95% CI [0.24, 0.84]). The certainty of evidence of these findings was generally low.
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A systematic review of tourniquet use in paediatric orthopaedic surgery: can we extrapolate from adult guidelines?
Pintar, V., Brookes, C., Trompeter, A., Bridgens, A., Hing, C., Gelfer, Y.
EFORT open reviews. 2024;9(1):80-91
Abstract
PURPOSE Tourniquets are commonly used intraoperatively in orthopaedic surgery to control bleeding and improve visibility in the surgical field. Recent evidence has thrown into question the routine use of tourniquets in the adult population resulting in a British Orthopaedic Association standard for intraoperative use. This systematic review evaluates the evidence on the practice, benefits, and risks of the intraoperative use of tourniquets for trauma and elective orthopaedic surgery in the paediatric population. METHODS A prospectively registered systematic review was conducted using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines (PROSPERO CRD42022359048). A search of MEDLINE, Embase, the Cochrane Library and a Grey literature search was performed from their earliest record to 23 March 2023. Studies reporting tourniquet data in paediatric patients undergoing orthopaedic surgery were included. Data extracted included demographics, involved limb, trauma versus elective use, tourniquet use as primary or secondary measure, and tourniquet parameters and complications. RESULTS Thirty-nine studies were included. Tourniquet practices and information reporting varied considerably. Tourniquets were used uneventfully in the majority of patients with no specific benefits reported. Several physiological and biochemical changes as well as complications including nerve injury, compartment syndrome, skin burns, thrombosis, post-operative limb swelling, and pain were reported. CONCLUSIONS Tourniquets are routinely used in both trauma and elective paediatric orthopaedic surgery with no high-quality research affirming benefits. Severe complications associated with their use are rare but do occur. High-quality studies addressing their benefits, the exact indication in children, and the safest way to use them in this population are necessary.
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The Effect of Tranexamic Acid and Controlled Hypotension on Perioperative Blood Loss in Craniosynostosis Surgery
Moradi Farsani, D., Mazaheri, Z., Shafa, A.
Anesthesiology and pain medicine. 2023;13(1):e130462
Abstract
BACKGROUND Open cranial vault reconstruction is the standard technique of craniosynostosis correction that may cause significant blood loss. OBJECTIVES The current study aimed at comparing the effect of tranexamic acid (TXA), controlled hypotension, and their combination on perioperative blood loss and transfusion requirement in craniosynostosis surgery. METHODS The present randomized, double-blind clinical trial was conducted on 75 infants referred for craniosynostosis surgery during 2017 - 2018. Ten minutes before the start of surgery, 10 mg/kg of TXA was administered intravenously to patients in the first group (TXA group). In the second group, patients were subjected to the controlled hypotension anesthesia (CHA) using intravenous remifentanil 0.1 μ/kg (CHA group). In the third group, the patients underwent CHA similar to that of the second group, along with intravenous injection of 10 mg/kg of TXA (CHA-TXA group). Then, patients' mean arterial pressure (MAP), heart rate (HR), total blood loss, and transfusion volume were evaluated and recorded. RESULTS The results of the present study revealed that although the changes in MAP and HR parameters over time (three hours after surgery) were significant in all three groups, the lowest decrease was observed in the CHA-TXA group (P-value < 0.05). In addition, the total perioperative blood loss in the CHA-TXA group with the mean of 181.20 ± 82.71 cc was significantly less than the total perioperative blood loss in the CHA and TXA groups with the means of 262.00 ± 104.04 cc and 212.80 ± 80.75 cc, respectively (P-value < 0.05). Moreover, the transfusion volume in the CHA-TXA group with the mean of 112.40 ± 53.50 cc was significantly lower than the transfusion volume in the CHA and TXA groups with the means of 174.00 ± 73.93 cc and 160.63 ± 59.35 cc, respectively (P-value < 0.05). In contrast, the total blood loss and transfusion volume were not significantly different between the CHA and TXA groups (P-value > 0.05). CONCLUSIONS According to the results of the present study, although the administration of TXA alone could effectively prevent blood loss and was associated with fewer transfusion requirements, the combination of this approach with hypotensive anesthesia resulted in more reduction in perioperative blood loss and transfusion volume as well as better hemodynamic stability.
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Endoscopic Primary Prophylaxis to Prevent Bleeding in Children with Esophageal Varices: A Systematic Review and Meta-Analysis
Alatas, F. S., Monica, E., Ongko, L., Kadim, M.
Pediatric gastroenterology, hepatology & nutrition. 2023;26(5):231-238
Abstract
PURPOSE This systematic review and meta-analysis aimed to compare endoscopy as primary versus secondary prophylaxis to prevent future bleeding in children with esophageal varices. METHODS A systematic literature search using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses method was conducted using the Scopus, PubMed, and Cochrane databases for relevant studies on the outcome of rebleeding events after endoscopy in primary prophylaxis compared to that in secondary prophylaxis. The following keywords were used: esophageal varices, children, endoscopy, primary prophylaxis and bleeding. The quality of eligible articles was assessed using the Newcastle-Ottawa Scale and statistically analyzed using RevMan 5.4 software. RESULTS A total of 174 children were included from four eligible articles. All four studies were considered of high-quality based on the Newcastle-Ottawa Quality Assessment Scale. Patients who received primary prophylaxis had 79% lower odds of bleeding than those who received secondary prophylaxis (odds ratio, 0.21; 95% confidence interval [CI], 0.07-0.66; I(2)=0%, p=0.008). Patients in the primary prophylaxis group underwent fewer endoscopic procedures to eradicate varices than those in the secondary prophylaxis group, with a mean difference of 1.73 (95% CI, 0.91-2.56; I(2)=62%, p<0.0001). CONCLUSION Children with high-risk varices who underwent primary prophylaxis were less likely to experience future bleeding episodes and required fewer endoscopic procedures to eradicate the varices than children who underwent secondary prophylaxis.
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Effects of delayed cord clamping at different time intervals in late preterm and term neonates: a randomized controlled trial
Chaudhary, P., Priyadarshi, M., Singh, P., Chaurasia, S., Chaturvedi, J., Basu, S.
European journal of pediatrics. 2023;:1-11
Abstract
Delayed cord clamping (DCC) at delivery has well-recognized benefits; however, current scientific guidelines lack uniformity in its definition. This parallel-group, three-arm assessor-blinded randomized controlled trial compared the effects of three different timings of DCC at 30, 60, and 120 s on venous hematocrit and serum ferritin levels in late preterm and term neonates not requiring resuscitation. Eligible newborns (n = 204) were randomized to DCC 30 (n = 65), DCC 60 (n = 70), and DCC 120 (n = 69) groups immediately after delivery. The primary outcome variable was venous hematocrit at 24 ± 2 h. Secondary outcome variables were respiratory support, axillary temperature, vital parameters, incidences of polycythemia, neonatal hyperbilirubinemia (NNH), need and duration of phototherapy, and postpartum hemorrhage (PPH). Additionally, serum ferritin levels, the incidence of iron deficiency, exclusive breastfeeding (EBF) rate, and anthropometric parameters were assessed during post-discharge follow-up at 12 ± 2 weeks. Over one-third of the included mothers were anemic. DCC 120 was associated with a significant increase in the mean hematocrit by 2%, incidence of polycythemia, and duration of phototherapy, compared to DCC30 and DCC60; though the incidence of NNH and need for phototherapy was similar. No other serious neonatal or maternal adverse events including PPH were observed. No significant difference was documented in serum ferritin, incidences of iron deficiency, and growth parameters at 3 months even in the presence of a high EBF rate. Conclusion: The standard recommendation of DCC at 30-60 s may be considered a safe and effective intervention in the busy settings of low-middle-income countries with a high prevalence of maternal anemia. Trial registration: Clinical trial registry of India (CTRI/2021/10/037070). What is Known: • The benefits of delayed cord clamping (DCC) makes it an increasingly well-accepted practice in the delivery room. • However, uncertainty continues regarding the optimal timing of clamping; this may be of concern both in the neonate and the mother. What is New: • DCC at 120 s led to higher hematocrit, polycythemia and longer duration of phototherapy, without any difference in serum ferritin, and incidence of iron deficiency. • DCC at 30-60 s may be considered a safe and effective intervention in LMICs.
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Low-Dose vasopressin and renal perfusion in pediatric cardiac surgery
Kumar, A., Ghotra, G. S., Raj, S., Tiwari, N., Ramamurthy, H. R.
Annals of cardiac anaesthesia. 2023;26(3):309-317
Abstract
BACKGROUND Congenital heart surgeries are associated with post-bypass renal and cardiac dysfunctions. The use of low-dose vasopressin has been found to be beneficial in adult cardiac surgeries. OBJECTIVE To assess the hemodynamic and renal effects of patients undergoing on-pump pediatric cardiac surgery under general anesthesia (GA) with low-dose vasopressin infusion. DESIGN Prospective randomized controlled study. SETTING Operation room and ICU, tertiary care teaching hospital. PATIENTS Fifty-five pediatric cardiac patients undergoing repair for congenital heart diseases (CHD). INTERVENTIONS Low-dose vasopressin infusion in the study group and placebo in the control group. MEASUREMENTS AND MAIN RESULTS Renal near-infrared spectroscopy (NIRS), serum NGAL, and inflammatory mediators-IL6 and IL8 along with other renal and hemodynamic parameters in the perioperative period were recorded. Diastolic blood pressure (DBP) and cardiac index were significantly higher in the vasopressin group. Inflammatory markers were significantly high in the immediate postoperative period in all patients which later stabilized in the next 48 h but showed similar trends in both groups. Low-dose vasopressin infusion did not improve either renal perfusion or function. The duration of mechanical ventilation and length of hospital stay, the incidence of AKI development, and transfusion requirements were marginally lower in the vasopressin group, although not significant. CONCLUSION Low-dose vasopressin infusion improved hemodynamics and showed a decreased incidence of complications. However, it failed to show any benefit of renal function and overall outcome in pediatric cardiac surgery.
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Tranexamic Acid in Hip Reconstructions in Children with Cerebral Palsy: A Double-Blind Randomized Controlled Clinical Trial
Zuccon, A., Rogério Cardozo Kanaji, P., Serafini Barcellos, D., Zabulon, S., de Oliveira Saraiva, A., Yoshi de Freitas, T. A.
Children (Basel, Switzerland). 2023;10(12)
Abstract
Surgical treatment is indicated for hip dislocation in patients with cerebral palsy (CP), but it requires care due to the state of nutrition and associated clinical comorbidities. The use of resources that minimize blood loss and the need for blood transfusions are essential to avoid complications. Tranexamic acid (TXA) has been highlighted for orthopedic surgeries to control intraoperative bleeding; however, there is a lack of large studies for its use in hip surgeries in patients with CP. This study aims to evaluate the efficacy and safety of tranexamic acid to reduce bleeding in pediatric patients with cerebral palsy undergoing surgical treatment for hip instability. A sample of 31 patients with CP who underwent surgical treatment for hip dislocation (hip adductor stretching, varization osteotomy of the proximal femur and acetabuloplasty using the Dega technique) was randomly divided into groups: control (n = 10) and TXA (n = 21). Preoperative and 24 h hemoglobin concentrations, the length of hospital stay (LHS), and intraoperative bleeding (IB) were analyzed. TXA significantly reduced the IB (p = 0.02). The variance in hemoglobin concentration was lower for the TXA group, but without statistical significance (p = 0.06). There was no difference in LHS. Also, no statistical difference was observed for the number of transfusions (p = 0.08). The findings provide evidence of the effectiveness of TXA in decreasing intraoperative bleeding and its safety for use in pediatric patients with cerebral palsy.
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BAY 81-8973 Efficacy and Safety in Previously Untreated and Minimally Treated Children with Severe Hemophilia A: The LEOPOLD Kids Trial
Ljung, R., Chan, A. K. C., Glosli, H., Afonja, O., Becker, B., Tseneklidou-Stoeter, D., Mancuso, M. E., Saulyte-Trakymiene, S., Kenet, G.
Thrombosis and Haemostasis. 2023;123(1):27-39
Abstract
INTRODUCTION BAY 81-8973, a full-length recombinant factor VIII for hemophilia A treatment, has been extensively evaluated in previously treated patients in the LEOPOLD (Long-Term Efficacy Open-Label Program in Severe Hemophilia A Disease) clinical trials. AIM: To assess BAY 81-8973 efficacy and safety when used for bleed prophylaxis and treatment in previously untreated/minimally treated patients (PUPs/MTPs). METHODS In this phase III, multicenter, open-label, uncontrolled study, PUPs/MTPs (<6 years old) with severe hemophilia A received BAY 81-8973 (15-50 IU/kg) at least once weekly as prophylaxis. Primary efficacy endpoint was the annualized bleeding rate (ABR) within 48 hours after prophylaxis infusion. Adverse events and immunogenicity were assessed. Patients who developed inhibitors were offered immune tolerance induction (ITI) treatment in an optional extension phase. RESULTS Fifty-two patients were enrolled, with 43 patients (mean age: 13.6 months) treated. Median (interquartile range) ABR for all bleeds within 48 hours of prophylaxis infusion was 0.0 (0.0-1.8) among patients without inhibitors (n = 20) and 0.0 (0.0-2.2) among all patients. As expected, inhibitors were the most frequent treatment-related adverse event (high titer: 17 [39.5%] patients; low titer: 6 [13.9%] patients). Six of 12 patients who underwent ITI treatment in the extension phase (high titer [n = 5], low titer [n = 1]) achieved a negative inhibitor titer. CONCLUSION BAY 81-8973 was effective for bleed prevention and treatment in PUPs/MTPs. The observed inhibitor rate was strongly influenced by a cluster of inhibitor cases, and consequently, slightly higher than in other PUP/MTP studies. Overall, the BAY 81-8973 benefit-risk profile remains unchanged and supported by ongoing safety surveillance. Immune tolerance can be achieved with BAY 81-8973.
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10.
Postnatal phenobarbital for the prevention of intraventricular haemorrhage in preterm infants
Romantsik O, Smit E, Odd DE, Bruschettini M
The Cochrane database of systematic reviews. 2023;3(3):Cd001691
Abstract
BACKGROUND Intraventricular haemorrhage (IVH) is a major complication of preterm birth. Large haemorrhages are associated with a high risk of disability and hydrocephalus. Instability of blood pressure and cerebral blood in the newborn flow are postulated as causative factors. Another mechanism may involve reperfusion damage from oxygen free radicals. It has been suggested that phenobarbital stabilises blood pressure and may protect against free radicals. This is an update of a review first published in 2001 and updated in 2007 and 2013. OBJECTIVES To assess the benefits and harms of the postnatal administration of phenobarbital in preterm infants at risk of developing IVH compared to control (i.e. no intervention or placebo). SEARCH METHODS We searched the Cochrane Central Register of Controlled Trials (CENTRAL), Medline, Embase, CINAHL and clinical trial registries in January 2022. A new, more sensitive search strategy was developed, and searches were conducted without date limits. SELECTION CRITERIA We included randomised controlled trials (RCTs) or quasi-RCTs in which phenobarbital was given within the first 24 hours of life to preterm infants identified as being at risk of IVH because of gestational age below 34 weeks, birth weight below 1500 g or respiratory failure. Phenobarbital was compared to no intervention or placebo. We excluded infants with serious congenital malformations. DATA COLLECTION AND ANALYSIS We used standard Cochrane methods. Our primary outcomes were all grades of IVH and severe IVH (i.e. grade III and IV); secondary outcomes were ventricular dilation or hydrocephalus, hypotension, pneumothorax, hypercapnia, acidosis, mechanical ventilation, neurodevelopmental impairment and death. We used GRADE to assess the certainty of the evidence for each outcome. MAIN RESULTS We included 10 RCTs (792 infants). The evidence suggests that phenobarbital results in little to no difference in the incidence of IVH of any grade compared with control (risk ratio (RR) 1.00, 95% confidence interval (CI) 0.84 to 1.19; risk difference (RD) 0.00, 95% CI -0.06 to 0.07; I² for RD = 65%; 10 RCTs, 792 participants; low certainty evidence) and in severe IVH (RR 0.88, 95% CI 0.64 to 1.21; 10 RCTs, 792 participants; low certainty evidence). The evidence is very uncertain about the effect of phenobarbital on posthaemorrhagic ventricular dilation or hydrocephalus (RR 0.62, 95% CI 0.31 to 1.26; 4 RCTs, 271 participants; very low certainty evidence), mild neurodevelopmental impairment (RR 0.57, 95% CI 0.15 to 2.17; 1RCT, 101 participants; very low certainty evidence), and severe neurodevelopmental impairment (RR 1.12, 95% CI 0.44 to 2.82; 2 RCTs, 153 participants; very low certainty evidence). Phenobarbital may result in little to no difference in death before discharge (RR 0.88, 95% CI 0.64 to 1.21; 9 RCTs, 740 participants; low certainty evidence) and mortality during study period (RR 0.98, 95% CI 0.72 to 1.33; 10 RCTs, 792 participants; low certainty evidence) compared with control. We identified no ongoing trials. AUTHORS' CONCLUSIONS The evidence suggests that phenobarbital results in little to no difference in the incidence of IVH (any grade or severe) compared with control (i.e. no intervention or placebo). The evidence is very uncertain about the effects of phenobarbital on ventricular dilation or hydrocephalus and on neurodevelopmental impairment. The evidence suggests that phenobarbital results in little to no difference in death before discharge and all deaths during the study period compared with control. Since 1993, no randomised studies have been published on phenobarbital for the prevention of IVH in preterm infants, and no trials are ongoing. The effects of postnatal phenobarbital might be assessed in infants with both neonatal seizures and IVH, in both randomised and observational studies. The assessment of benefits and harms should include long-term outcomes.