Indomethacin Therapy Research Articles

How does ibuprofen compare with standard indomethacin therapy for preterm/low birth weight infants with patent ductus arteriosus (PDA)?

How does ibuprofen compare with standard indomethacin therapy for preterm/low birth weight infants with patent ductus arteriosus (PDA)?

Urinary acute kidney injury biomarkers in very low-birth-weight infants on indomethacin for patent ductus arteriosus.

Serum creatinine (SCr)- or urine output-based definitions of acute kidney injury (AKI) have important limitations in neonates. This study evaluates the diagnostic value of urinary biomarkers in very low-birth-weight (VLBW) infants receiving indomethacin for closure of a patent ductus arteriosus (PDA). Prospective cohort study in 14 indomethacin-treated VLBW infants and 18 VLBW infants without indomethacin as controls. Urinary biomarkers were measured before, during, and after indomethacin administration. Indomethacin therapy was associated with significantly higher SCr concentrations at 36, 84, and 120 h compared to controls. At 36 h, three indomethacin-treated patients met the criteria for neonatalmodified Kidney Disease: Improving Global Outcomes (KDIGO) AKI. The product of urinary tissue inhibitor of metalloproteinase-2 and insulin-like growth factor-binding protein 7 ([TIMP-2]•[IGFBP7]) was significantly elevated in the AKI subgroup at 12 h (P < 0.05), hence 24 h earlier than the increase in SCr. Urinary neutrophilgelatinase-associated lipocalin (NGAL) and calprotectin were significantly increased in the indomethacin group at 12 h (P < 0.05), irrespective of fulfillment of the AKI criteria. Urinary kidney injury molecule-1 (KIM-1) was not significantly altered. While urinary [TIMP-2]•[IGFBP7] proves valuable for the early diagnosis of neonatal modified KDIGO-defined AKI, elevated urinary NGAL and calprotectin concentrations in indomethacin-treated VLBW infants not fulfilling the AKI criteria may indicate subclinical kidney injury.

Rectally administered indomethacin to prevent post-ESWL-pancreatitis (RIPEP): study protocol for a randomized controlled trial

BackgroundPancreatic extracorporeal shock wave lithotripsy (P-ESWL) is the first-line therapy for large pancreatic duct stones. Although it is a highly effective and safe procedure for the fragmentation of pancreatic stones, it is still not complication-free. Just like endoscopic retrograde cholangiopancreatography (ERCP), pancreatitis is the most common complication. To date, nonsteroidal anti-inflammatory drugs (NSAIDs) have proven to be the only effective prophylactic medication for post-ERCP pancreatitis and the European, American and Japanese Society for Gastrointestinal Endoscopy guidelines have recommended prophylactic rectally administered indomethacin for all patients undergoing ERCP. Given the little research about effective prevention for post P-ESWL pancreatitis, we aim to determine whether rectally administered indomethacin can reduce post-ESWL-pancreatitis.Methods/designThe RIPEP study is a prospective, randomized, double-blinded, placebo-controlled trial. One thousand three hundred and seventy patients with chronic pancreatitis and pancreatic stones (>5 mm in diameter) treated with P-ESWL at Changhai Hospital will be randomly allocated to rectally administered indomethacin or placebo therapy before the procedure. The primary endpoint is the incidence of post-ESWL pancreatitis. Secondary endpoints include the severity of pancreatitis, occurrence rate of asymptomatic hyperamylasemia and other complications.DiscussionThe RIPEP trial is designed to show that rectally administered indomethacin reduces the development and severity of post-ESWL pancreatitis and benefits patients treated with P-ESWL.Trial registrationClinicalTrials.gov, ID: NCT02797067. Registered on 17 November 2016.

P29.09: The use of long‐term indomethacin stabilises cervical length in twin pregnancies

To determine if the use of early onset (less than 25 weeks) long-term indomethacin therapy (greater than 48 hours) (LIT) stabilises the cervical length (CL) in dichorionic-diamniotic twin gestations (DCDA-T) that are complicated by a short cervix. DCDA-T pregnancies with short CL (less than 30mm) after 18 weeks were identified. Serial CL measurements, other treatments (17 OH-P, vaginal progesterone, nifedipine) and outcomes were collected. Patients with cervical cerclage were excluded. The degree of cervical shortening from initial to last examination was compared in patients with a short CL and women with a normal CL at same gestational age (GA). Longitudinal analysis of the change in CL was modelled using mixed-model regression analysis and predicted values were compared using comparisons of the slope analysis. Out of 63 patients, 25 (40%) received LIT. The GA at initial ultrasound was similar between groups (P=0.6). There were no differences between the two groups regarding history of preterm birth and use of progesterone or nifedipine. The initial and last CLs were shorter in LIT group (24mm vs 43mm and 10mm vs 36.5mm). The average duration of indocin use was 49 days. A total of 255 (LIT=165, Normal CL=90) longitudinal CL examinations were used for mixed-model regression analysis. CL improved or did not change in LIT group (0-0.6mm/week)(CL= -0.0003GA2 + 0.7292GA - 0.0458, R2=0.046). However, in normal CL group, CL declined by 0.06-1.9mm/w (CL=0.091GA2 - 5.98GA+126.14, R2=0.21)(p<0.001). There were no reportable antenatal side effects. Early onset long-term indomethacin therapy in DCDA-T with a short cervix provides an alternative treatment modality to stabilise cervix.

Melanin binding study of clinical drugs with cassette dosing and rapid equilibrium dialysis inserts

Melanin pigment is a negatively charged polymer found in pigmented human tissues. In the eye, iris, ciliary body, choroid and retinal pigment epithelium (RPE) are heavily pigmented. Several drug molecules are known to bind to melanin, but larger sets of drugs have not been compared often in similar test conditions. In this study, we introduce a powerful tool for screening of melanin binding. The binding of a set of 34 compounds to isolated porcine RPE melanin was determined by cassette (n-in-one) dosing in rapid equilibrium dialysis inserts and the binding was quantitated with LC-MS/MS analytics. The compounds represented large variety in melanin binding (from 8.6%, ganciclovir) to over 95% bound (ampicillin and ciprofloxacin). The data provides information on melanin binding of small molecular weight compounds that are used for ocular (e.g. brinzolamide, ganciclovir) and systemic (e.g. tizanidine, indomethacin) therapy. Interestingly, competition among compounds was seen for melanin binding and the binding did not show any correlation with plasma protein binding. These results increase the understanding of melanin binding of ocular drugs and can be further exploited to predict pharmacokinetics in the eye. Pigment binding provides an interesting option for improved drug distribution to retina and choroid that are difficult target tissues in drug delivery.

The Use of Long-Term Indomethacin Stabilizes Cervical Length in Twin Pregnancies [7Q

INTRODUCTION: To determine if the use of early onset (less than 25 weeks) long-term indomethacin therapy (greater than 48 hours) (LIT) stabilizes the cervical length (CL) in dichorionic-diamniotic twin gestations (DCDA-T) that are complicated by a short cervix. METHODS: DCDA-T pregnancies with short CL (less than 30 mm) after 18 weeks were identified. Serial CL measurements, other treatments (17 OH-P, vaginal progesterone) and outcomes were collected. Patients with cervical cerclage were excluded. The degree of cervical shortening from initial to last examination was compared in patients with a short CL and women with a normal CL at same gestational age (GA). Longitudinal analysis of the change in CL was modeled using mixed-model regression analysis and predicted values were compared using comparisons of the slope analysis. RESULTS: Out of 77 patients, 32 (42%) received LIT. The GA at initial ultrasound was similar between groups (P=0.6). Initial and last CLs were shorter in LIT group (21 mm vs 43 mm and 11.5 mm vs 36 mm) (P &lt; .0001 for both). A total of 434 (LIT=191, Normal CL=243) longitudinal CL examinations were used for mixed-model regression analysis. CL improved or did not change in LIT group (0-0.4 mm/week) (CL= 0.0353GA2-1.5458GA+32.399, R2=0.06). However, in normal CL group, CL was declined by 0.8-1.9 mm/w (CL=0.0529GA2-4.1356x+105.25) (P &lt; .00001). There were no reportable antenatal side effects. CONCLUSION: Early onset long-term indomethacin therapy in DCDA-T with a short cervix provides an alternative treatment modality to stabilize cervix.

Comparative effectiveness of aggressive intravenous fluid resuscitation with lactated Ringer's solution and rectal indomethacin therapy in the prevention of pancreatitis after endoscopic retrograde cholangiopancreatography: a double blind randomised controlled clinical trial.

IntroductionThere is growing evidence indicating the aggressive intravenous fluid resuscitation (IVFR) can decrease the rate of pancreatitis; however, to the best of our knowledge it has not been well studied in a post-endoscopic retrograde cholangiopancreatography (post-ERCP) setting.AimTo compare the effects of aggressive IVFR and rectal indomethacin (RI) in preventing pancreatitis after ERCP.Material and methodsThis is a double blind randomised controlled clinical trial on 186 patients undergoing ERCP in Ahvaz, Iran. The inclusion criteria were ERCP for standard clinical indications such as choledocholithiasis, bile duct leak, and biliary obstruction. The IVFR group (n = 62) received a bolus of 20 ml/kg of body weight lactated Ringer’s solution (LRS) immediately after ERCP, followed by 3 ml/kg/h maintenance for 8 h. The RI group (n = 62) received 50 mg rectal indomethacin immediately before procedure and 12 h after ERCP. The control group (n = 62) did not receive any treatment.ResultsPost-ERCP pancreatitis in IVFR, rectal indomethacin, and control groups occurred in 8 (12.9%), 16 (25.8%), and 20 (32.3%) patients (p = 0.036). Pancreatic pain was reported in 13 (21%), 21 (33.9%), and 27 (43.5%) patients in the IVFR, RI, and control group (p = 0.046). The serum amylase level increased over 24 h after intervention in all three groups. The mean serum amylase level 8 h after intervention in the IVFR patients was lower than the RI and control groups.ConclusionsIntravenous fluid resuscitation with LRS was more effective in preventing post-ERCP pancreatitis in comparison to the rectal indomethacin and control group.

Enteral feeding during indomethacin treatment for patent ductus arteriosus: association with gastrointestinal outcomes.

Enteral feeds are often discontinued or reduced during indomethacin treatment for patent ductus arteriosus (PDA) in preterm neonates, but the clinical impact of this practice is unknown. The objective of this study was to study the associations between enteral feed volume at the time of indomethacin therapy in preterm neonates with PDA and subsequent gastrointestinal outcomes. Retrospective cohort study. Single-center level III Neonatal Intensive Care Unit. All consecutive preterm neonates who had received treatment with indomethacin for PDA over a 5-year period were included and categorized based on enteral feed volume exposure during treatment (Group A: nil per oral (NPO, N=229); Group B: ⩽60 ml kg(-1) day(-1) (N=142); Group C:>60 ml kg(-1) day(-1) (N=44)). Baseline characteristics and clinical outcomes were compared between the three groups. The primary outcome was necrotizing enterocolitis (NEC) ⩾stage IIa, while secondary outcomes included other gastrointestinal complications and common prematurity-related morbidities. Group C had a higher gestational age (mean±s.d.; A: 26.3±1.8; B: 26.1±1.8; C: 27.0±2.0 weeks), birth weight (A: 864±239; B: 847±202; C: 932±234 g) and postnatal age at the time of indomethacin treatment (A: 5.3±2.9; B: 7.2±4.9; C: 15.4±6.6 days). All groups had similar rates of the primary outcome NEC (A: 6.1%, B: 7.8% and C: 4.6%, respectively). They also had similar rates of the secondary outcomes with the exception of days to reach enteral feeds of 120 ml kg(-1) day(-1) (A: 22.8±8.5; B: 20.5±8.6; C: 16.8±7.7; P<0.05 for all inter-group comparisons). Secondary analysis including only those neonates who were not already NPO before indomethacin treatment (N=261) and categorized based on preemptive management (made NPO; enteral feed volume reduced; enteral feed volume unchanged/increased) also showed similar results. This large retrospective study did not identify any association between enteral feed volumes during indomethacin treatment or preemptive reduction in enteral feeds and subsequent incidence of adverse gastrointestinal outcomes in preterm neonates. Preemptive reduction in enteral feed volume was associated with longer time to reach full enteral feeds.

Familial mutation in Caffey disease with reduced penetrance: A case report.

Caffey disease is a rare condition of early infancy, characterized by soft tissue swelling, bone lesions, and hyperirritability. Its typical radiological finding is periosteal new bone formation. It can be sporadic or inherited in an autosomal dominant manner. There is no specific treatment. In symptomatic cases, non-steroidal anti-inflammatory drugs such as ibuprofen, indomethacin, or naproxen can be used. This is a report of an infant who presented with restlessness, irritability, and swelling over his shins, diagnosed as Caffey disease. Although there was no family history, the genetic analysis revealed heterozygous missense mutation (c.3040C > T) in type-I-collagen-alpha-1-chain gene in the patient in addition to his mother, grandmother, aunt, and cousin. After indomethacin therapy, the complaints of the patient were completely resolved and his bone lesions were significantly improved. This case report is a familial form of Caffey disease from Turkey, with proven heterozygous mutation in the patient and the family members.

A Case Report on Neonatal Bartter Syndrome and It’s Effective Management-Clinical Pharmacist Perspective

Bartter Syndrome is an inherited renal tubular disorder with hypokalaemia, hypochloremic and metabolic alkalosis. The syndrome was diagnosed by elevated serum renin levels, which is seen in our case, improved with potassium supplements and Indomethacin. In some patients Indomethacin therapy failed to resolve or prevent nephrocalcinosis. We are reporting a case of neonatal bartter syndrome responded well to Indomethacin and appropriate electrolyte therapy which gradually improved the general condition of the child. Unless there is a high degree of suspicion, patients may go undiagnosed or may be incorrectly managed for protein–energy malnutrition. Early diagnosis helps in improving the outcome by Angiotensin converting enzyme inhibitors (ACE) and NSAID’s.

425: Obesity does not impair indomethacin treatment of short cervix and preterm labor

Obesity is a state of increased inflammation. Our protocol of long-term indomethacin therapy to prevent preterm delivery prolongs pregnancy in the overall cohort. We sought to identify if obesity impacted the efficacy of this anti-inflammatory tocolytic medication.

Clinical analysis of 9 children with Pseudo-Bartter syndrome

Objective To analyze the clinical characteristics of children's Pseudo-Bartter syndrome(PBS) in order to enhance physician's understanding of the disease. Methods Nine children with PBS who were admitted into Beijing Children's Hospital from Nov.2008 to Sep.2013 were selected as research subjects.A retrospective study was carried out with the clinical data and the outcome of treatment. Results 1.Clinical characteristics: there were 9 cases in this group including 5 male and 4 female.The patients' age ranged from 4 months to 8 years 8 months.The most common cause of children's PBS was gastrointestinal symptoms(such as diarrhea and vomiting) induced by respiratory tract infection(7/9 cases). Six patients had no striking clinical manifestations, and hypokalemia was found in the treatment of primary disease.2.Laboratory tests: All of the children in this group had hypokalemia and metabolic alkalosis in varying degrees.The activation of renin, angiotensin and aldosterone system increased.3.Therapy: all children were treated by giving potassium supplemental treatment or indomethacin therapy [1 mg/(kg·d), 3 times orally]. After treatment, all cases achieved clinical improvement and normal blood electrolytes.All patients' blood electrolytes remained normal for 5 to 7 days after stopping treatment. Conclusions 1.In China, the most common cause of children's PBS is gastrointestinal symptoms(such as diarrhea and vomiting) induced by respiratory tract infection.2.Except for clinical manifestations related to causes, patients have no significant clinical manifestations.Hypokalemia can be found in the treatment of primary disease.3.The biochemical results show low blood potassium chloride with metabolic alkalosis.In PBS renin, angiotensin and aldosterone concentration in blood are all elevated.4.Treatment of children's PBS mainly includes etiolo-gical treatment and electrolyte supplement therapy.The treatment effectiveness is good after etiological treatment and potassium supplement treatment.In the condition of controlling etiology and potassium supplementation, electrolytes mas return to normal in 2-4 days. Key words: Pseudo-Bartter syndrome; Hypokalemia; Metabolic alkalosis

Is Preoperative Radiation Therapy as Effective as Postoperative Radiation Therapy for Heterotopic Ossification Prevention in Acetabular Fractures?

Prophylactic approaches to prevent heterotopic ossification after acetabular fracture surgery have included indomethacin and/or single-dose external beam radiation therapy administered after surgery. Although preoperative radiation has been used for heterotopic ossification prophylaxis in the THA population, to our knowledge, no studies have compared preoperative and postoperative radiation therapy in the acetabular fracture population. We determined whether heterotopic ossification frequency and severity were different between patients with acetabular fracture treated with prophylactic radiation therapy preoperatively and postoperatively. Between January 2002 and December 2009, we treated 320 patients with a Kocher-Langenbeck approach for acetabular fractures, of whom 50 (34%) were treated with radiation therapy preoperatively and 96 (66%) postoperatively. Thirty-four (68%) and 71 (74%), respectively, had 6-month radiographs available for review and were included. For hospital logistical reasons, patients who underwent operative treatment on a Friday or Saturday received radiation therapy preoperatively, and all others received it postoperatively. The treatment groups were comparable in terms of most demographic parameters, injury severity, and fracture patterns. Six-month postoperative radiographs were reviewed and graded according to Brooker. Followup ranged from 6 to 93 months and 6 to 97 months for the preoperative and postoperative groups, respectively. Post hoc power analysis showed our study was powered to detect a difference of 22% or more between patients with severe heterotopic ossification. Sample size calculations showed 915 subjects would be needed to detect a 5% relative difference in severe heterotopic ossification status between groups. We detected no difference in heterotopic ossification frequency between the preoperative (eight of 36, 22%) and postoperative (19 of 71, 27%) groups (p=0.609). There was also no difference in heterotopic ossification severity between groups (p=0.666). Two of 36 (6%) in the preoperative group and three of 71 (4%) in the postoperative group developed clinically significant Grade III heterotopic ossification. No patients developed Grade IV heterotopic ossification. We found no difference in heterotopic ossification frequency or severity when comparing preoperative and postoperative radiation therapy. However, given the relatively low frequency of heterotopic ossification in this population, in particular the frequency of severe or symptomatic heterotopic ossification, the possibility of a Type II error must be considered. Larger, prospective studies are required to confirm our no-difference finding, but insofar as the result in this fracture population mirrors that of the THA population, unless our finding is disproven, we believe radiation therapy can be given either before or after surgery, as dictated by the clinical scenario. Level III, therapeutic study. See Instructions for Authors for a complete description of levels of evidence.

Survival and Neurodevelopmental Outcome of Preterm Infants Born at 22-24 Weeks of Gestational Age

Background: The limits of viability in extremely premature infants are challenging for any neonatologists in developed countries. The neurological development and growth of extremely preterm infants have come to be the emerging issue following the management in the neonatal intensive care unit. Objective: To assess potential associations between changes in practice and survival/neurodevelopmental outcome, and clinical outcomes of extremely preterm infants born at the limit of viability studied in a tertiary center. Study Design: A retrospective study enrolled 51 infants who had no congenital disorders, and were born at 22-24 weeks of gestational age (GA) in 2000-2009 in our institution. Clinical variables and interventions were studied with regard to one-year survival and developmental quotient (DQ) at 3 years of age. Results: The one-year survival rate of 24 preterm infants born in 2005-2009 (79%) was higher than that of the 27 infants born in 2000-2004 (52%, p = 0.04). Infants born after 2005 underwent less tocolysis (54 vs. 94%, p < 0.01) and more frequently antenatal steroid therapy (32 vs. 6%, p = 0.01) than those born before 2004. The post-2005 survivors (n = 19) received more frequently indomethacin therapy (89 vs. 50%, p = 0.03) and early parenteral nutrition (95 vs. 36%, p < 0.01) than the pre-2004 survivors (n = 14). There were no differences in the proportion of infants who attained a DQ of >50 at 3 years of age between pre-2004 (9/13, 69%) and post-2005 groups (10/17, 59%). Multivariate analysis indicated that extremely premature birth at GA <24 weeks was the sole critical factor for a DQ of >50 in survivors. Conclusions: The perinatal care after 2005 improved the overall survival rate, but not the neurological outcome of preterm survivors at the limit of viability. Neurodevelopmental impairments were associated with extremely premature birth at GA <24 weeks.

Melatonin Responsive Hemicrania Continua in Which Indomethacin Was Associated With Contralateral Headache

Headache is a well-documented side effect of indomethacin in the older medical literature; however, it has rarely been commented on in indomethacin-responsive hemicrania continua. We describe the case of a 60-year-old woman with left-sided hemicrania continua whose indomethacin treatment was associated with a continuous right-sided migraine. Her indomethacin therapy was discontinued heralding a return of her left-sided hemicrania continua and a resolution of her right-sided migraine. Her hemicrania continua then responded well to melatonin, with recurrence on stopping and improvement on restarting. This is the most detailed description of headache as a side effect of indomethacin in a headache patient we are aware of, and one of only a few reported cases of melatonin-responsive hemicrania continua. We review the evidence of headache as a side effect of indomethacin in order to highlight its importance in the treatment of headache disorders. We emphasize that indomethacin headache response may be more than simply a beneficial or neutral one and might be relevant to some cases of apparently indomethacin-resistant hemicrania continua. We hope this case may encourage clinicians to inquire about headache as a potential side effect of indomethacin.

A Predictive Model for SIVH risk in Preterm Infants and Targeted Indomethacin Therapy for Prevention

Prophylactic indomethacin may decrease Severe Intraventricular Hemorrhage (SIVH). Our goal was to develop a predictive model for SIVH using parameters available by six hours of age. De-identified data for preterm infants born ≤ 34 weeks gestational age was abstracted from Vermont Oxford Network database. Using clinical variables available by 6 hrs of age the model was developed, and validated. Statistical methods were used to evaluate the ability of the model to discriminate infants with and without SIVH and, to compare observed and predicted risk. The model achieved excellent discrimination as indicated by ROC curve of 0·85. A good agreement was noted between observed and predicted risk (HLtest: p = 0·22). Application of the model to patients receiving indomethacin suggests a benefit at the highest risk levels. We have developed a valid predictive model for predicting SIVH as well as shown that exposure to indomethacin decreases the incidence of SIVH overall.

Chinese Herbal Medicine in Treatment of Polyhydramnios: a Meta-analysis and Systematic Review

To compare the efficacy of Chinese herbal medicine (therapy A) or Chinese herbal medicine plus indomethacin (therapy B) with that of indomethacin alone (therapy C) in treating polyhydramnios. Literatures published up to April 2012 were retrieved from PubMed, Embase and Cochrane library, Chinese National Knowledge Infrastructure (CNKI), Chinese Scientific and Technological Periodical Database (VIP), Wangfang, and Traditional Chinese Medicine online. Two researchers collected data independently. The assessment of methodological quality was based on Cochrane handbook and the materials were analyzed with software RevMan 5.1.2. The outcome measure index was relative risk or difference of mean value (95% confidence interval). The following outcomes were evaluated (1) general clinical improvement rate; (2) maximum vertical pocket depth; (3) amniotic fluid index (AFI) value; (4) rate of fetal ductus arteriosus constriction; (5) incidence of adverse events. Based on the search strategy, 5 trails involving 1017 patients were finally included. Compared with therapy C, therapy A decreased the rate of fetal ductus arteriosus constriction (P<0.01). Therapy B was more effective than therapy C in general clinical improvement and decrease of AFI for polyhydramnios (P<0.01). No serious adverse events were reported in therapy A and therapy B. Compared with therapy C, therapy A and therapy B may appear to be more effective for polyhydramnios. However, the exact effect needs to be confirmed with well-designed large-scale clinical trials.

Preservation of the metabolic rate of oxygen in preterm infants during indomethacin therapy for closure of the ductus arteriosus

The aim of this study was to assess and quantify the effects of indomethacin on cerebral blood flow (CBF), oxygen extraction fraction (OEF), and cerebral metabolic rate of oxygen (CMRO2) in preterm infants undergoing treatment for a patent ductus arteriosus (PDA). CBF and CMRO2 were measured before and after the first dose of a 3-d course of indomethacin to close hemodynamically significant PDA in preterm neonates. Indocyanine-green (ICG) concentration curves were acquired before and after indomethacin injection to quantify CBF and CMRO2. Eight preterm neonates (gestational age, 27.6 ± 0.5 wk; birth weight, 992 ± 109 g; 6 males:2 females) were treated at a median age of 4.5 d (range, 4-21 d). Indomethacin resulted in an average CBF decrease of 18% (pre- and post-CBF = 12.9 ± 1.3 and 10.6 ± 0.8 ml/100 g/min, respectively) and an OEF increase of 11% (pre- and post-OEF = 0.38 ± 0.02 and 0.42 ± 0.02, respectively) but no significant change in CMRO2 (pre- and post-CMRO2 = 0.83 ± 0.07 and 0.76 ± 0.07 ml O2/100 g/min, respectively). Corresponding mean blood pressure (BP), arterial oxygen saturation (SaO2), heart rate, and end-tidal carbon dioxide tension levels remained unchanged. Indomethacin resulted in significant reduction in CBF but did not alter CMRO2 because of a compensatory increase in OEF.

Heterotopic Ossification Rates After Acetabular Fracture Surgery Are Unchanged Without Indomethacin Prophylaxis

We previously found no reduction in heterotopic ossification (HO) rates after acetabular surgery with indomethacin compared with a placebo. We subsequently abandoned routine indomethacin therapy after acetabular surgery but questioned whether the incidence had changed using a posterior approach. We therefore determined (1) the incidence of HO after acetabular fracture surgery through a posterior approach; (2) the incidence of symptoms attributable to HO; and (3) the rate of reoperation for HO. We retrospectively reviewed the records of all 423 patients with acetabular fractures following our clinical protocol change; of these, 120 were treated with a Kocher-Langenbeck approach and included. The presence of radiographic HO was documented a minimum of 10 weeks postoperatively using the classification of Brooker et al. Symptoms and reoperations were recorded. The overall incidence of radiographic HO was 47% (56 of 120 patients): 26% Class I-II 13% Class III, and 8% Class IV. Overall, 15% of patients developed symptoms; 3.3% underwent reoperations for excision of HO. There were no major differences between the incidence of moderate and severe HO in this study when compared with the indomethacin and placebo groups from the prior study. Our incidence of moderate and severe HO has not changed since discontinuing indomethacin. These findings support our institutional decision to abandon routine indomethacin prophylaxis after acetabular surgery. We recommend improved surgical techniques to limit damage to the abductors and improved risk stratification of patients when considering treatment options for HO prophylaxis.

Effects of Indomethacin on Patent Ductus Arteriosus in Neonates with Genetic Disorders and/or Congenital Anomalies

The study aimed to evaluate the effectiveness of intravenous indomethacin (IND) therapy for patent ductus arteriosus (PDA) in neonates with genetic disorders and/or congenital anomalies soon after birth. A total of 301 neonates with a genetic disorder and/or congenital anomalies and with a gestational age of ≥ 35 weeks were admitted during the study period. Eighty-five neonates with 56 genetic disorders (30 cases of trisomy 21, 10 cases of trisomy 18, and 16 others) and 29 congenital anomalies, and with clinical symptoms received intravenous IND therapy. The management methods were similar to those used for PDA in low-birth-weight infants. IND therapy had a clinical benefit at a high rate of 79% in these patients (90% and 70% in neonates with trisomies 21 and 18, respectively), including complete closure of the PDA in 52% of the patients. Although oliguria was observed in 43 infants (51%) and slight gastrointestinal bleeding was observed in 12 (14%), no infants had severe complications such as intracranial bleeding. IND therapy is an effective treatment option before considering surgery for PDA in neonates with genetic disorders and/or congenital anomalies. This therapy may reduce the difficulty of treatment in the acute stage among these neonates.