The use of ketorolac may reduce opioid exposure in infants less than 6 months of age undergoing congenital heart surgery.

OBJECTIVES: Pain management for infants undergoing cardiothoracic surgery primarily utilises opioid analgesics. There is a paucity of data available for the use of non-steroidal anti-inflammatory medications such as ketorolac in this patient population. MATERIALS AND METHODS: This retrospective study evaluated patients between 30 days and 6 months undergoing cardiothoracic surgery. The primary endpoint evaluates ketorolac on reducing post-operative opioid use. RESULTS: Of 243 evaluated patient, 145 met inclusion. Baseline demographics were similar amongst the cohorts. Patients administered ketorolac used less cumulative opiates, in morphine milligram equivalents, for post-op days (POD) 1-3 after surgery compared to patients not receiving ketorolac (9.47 versus 12.68; p = 0.002). The no-ketorolac group required more opiates on POD 1 (10.9 versus 5; p < 0.001) and POD 2 (4.2 versus 2.5; p = 0.006) with no difference found on POD 3 (2 versus 1.6; p = 0.2). There was a mean increase from baseline to highest serum creatinine level on POD 1-3 in the no-ketorolac group compared to the ketorolac group (0.15 versus 0.09 mg/dL; p < 0.014), with no difference in stage 1 or stage 2 acute kidney injury. There were no differences in average chest tube output in mL/kg/day (0.24 versus 0.32; p = 0.569) or need for transfusion (36% versus 24%; p = 0.125), respectively. DISCUSSION: Scheduled administration of ketorolac after cardiothoracic surgery resulted in a significant reduction in opioid exposure, with no difference in rates of acute kidney injury or bleeding.

Safety and Efficacy of Gabapentin for Pain in Pediatric Patients: A Systematic Review.

CONTEXT: Gabapentin has shown benefits for a variety of pain etiologies in adult patients, with off-label use as an adjunctive agent in pediatric patients occurring more frequently. OBJECTIVES: To summarize the studies which evaluate safety and efficacy of gabapentin for the treatment of pediatric pain. DATA SOURCES: A systematic review of the literature was conducted via PubMed query with controlled vocabulary and key terms using indexed medical subject heading. STUDY SELECTION: Prospective studies published between January 1, 2000, and July 1, 2023, were selected utilizing a predetermined exclusion criteria independently by 2 authors, with a third independent author available for discrepancies. DATA EXTRACTION: Data extraction was performed by 2 authors independently to include study design, patient population and characteristics, drug dosing, and outcomes. Studies were then assessed for their independent risk of bias utilizing the Grading of Recommendations, Assessment, Development, and Evaluations approach to risk of bias. RESULTS: A total of 11 studies describing 195 pediatric patients who received gabapentin were included. Of the 11 studies, 9 were randomized controlled trials, 1 was a prospective multicenter study, and 1 was an open-label pilot study. CONCLUSIONS: Heterogeneity of pain type and gabapentin dosing regimens within the included studies made conclusions difficult to quantify. Efficacy likely depends significantly on etiology of pain; however, per these studies, gabapentin is likely safe to use for a variety of pediatric patient populations as a multimodal agent.

Novel Dosing and Monitoring of Aspirin in Infants With Systemic-to-Pulmonary Artery Shunt Physiology: the SOPRANO Study.

OBJECTIVES: Provision of pulmonary blood flow with a systemic-to-pulmonary artery shunt is essential in some patients with cyanotic congenital heart disease. Traditionally, aspirin (ASA) has been used to prevent thrombosis. We evaluated ASA dosing with 2 separate antiplatelet monitoring tests for accuracy and reliability. METHODS: This is a retrospective, pre-post intervention single center study. Two cohorts were evaluated; the pre-intervention group used thromboelastography platelet mapping (TPM) and post-intervention used VerifyNow aspirin reactivity unit (ARU) monitoring. The primary endpoint was to compare therapeutic effect of TPM and ARU with regard to platelet inhibition. Inadequate platelet inhibition was defined as TPM <50% inhibition and ARU >550. RESULTS: Data from 49 patients were analyzed: 25 in the TPM group and 24 in the ARU group. Baseline characteristics were similar amongst the cohorts. The TPM group had significantly more patients with inadequate platelet inhibition (14 [56%] vs 2 [8%]; p = 0.0006) and required escalation with additional thromboprophylaxis (15 [60%] vs 5 [21%]). There was no difference in shunt thrombosis (1 [2%] vs 0 [0%]; p = 0.32), cyanosis requiring early re-intervention (9 [36%] vs 14 [58%]; p = 0.11), or bleeding (15 [60%] vs 14 [58%]; p = 0.66). CONCLUSION: With similar cohorts and the same ASA-dosing nomogram, ARU monitoring resulted in a reduced need for escalation of care and concomitant thromboprophylaxis with no difference in adverse outcomes. Our study suggests ARU monitoring compared with TPM may be a more reliable therapeutic platelet inhibition test for determining ASA sensitivity in children with congenital heart disease requiring systemic-to-pulmonary artery shunt.

Use of Aminophylline to Reverse Acute Kidney Injury in Pediatric Critical Care Patients.

OBJECTIVE: Acute kidney injury (AKI) is a complication encountered in 18% to 51% of pediatric critical care patients admitted for treatment of other primary diagnoses and is an independent risk factor for increased morbidity and mortality. Aminophylline has shown promise as a medication to treat AKI, but published studies have shown conflicting results. Our study seeks to assess the reversal of AKI following the administration of aminophylline in critically ill pediatric patients. METHODS: We performed a single-institution retrospective chart review of pediatric inpatients who were diagnosed with AKI and subsequently treated with non-continuous dose aminophylline between January 2016 and December 2018. Data were collected beginning 2 days prior to the initial dose of aminophylline through completion of the 5-day aminophylline course. RESULTS: Nineteen therapies among 17 patients were included in analysis. Twelve of the therapies resulted in resolution of AKI during the study period. We observed urine output increase of 19% (p = 0.0063) on the day following initiation of aminophylline therapy in the subset of patients whose AKI resolved. Trends toward decreased serum creatinine and lower inotropic support were also noted. CONCLUSIONS: Based on these findings, aminophylline could be considered a potentially effective medication for use as rescue therapy in critically ill children with AKI. Limitations include small study population and retrospective nature. Further research in this area with a larger study population and a randomized control trial would allow for better characterization of the efficacy of aminophylline in reversal of AKI.

Challenges of Antibiotic Stewardship in the Pediatric and Neonatal Intensive Care Units.

The goals of antimicrobial stewardship programs (ASPs) are to optimize antimicrobial prescribing habits in order to improve patient outcomes, reduce antimicrobial resistance, and reduce hospital costs. Multiple society-endorsed guidelines and government policies reinforce the importance of ASP implementation. Effective antimicrobial stewardship can impact unique patients, hospitals, and societal antibiotic-resistance burden. The role and subsequent success of these programs has largely been reported in the adult population. Pediatric and neonatal intensive care units present unique challenges for traditional antimicrobial stewardship approaches. The purpose of this review article is to explore the challenges of appropriate antibiotic use in the pediatric and neonatal intensive care units and to summarize strategies ASPs can use to overcome these challenges. These problems include non-specific disease presentations, limited evidence for definitive treatment durations in many pediatric infections, fewer pediatric-trained infectious disease physicians, and applicability of intensive laboratory obtainment, collection, and interpretation. Additionally, many ASP implementation studies evaluating the efficacy of ASPs exclude the PICU and NICU. Areas of focus for pediatric ASPs should likely include appropriate antibiotic initiation, appropriate antibiotic duration, and appropriate antibiotic de-escalation.

Efficacy and Safety of Non-Vitamin K Antagonist Oral Anticoagulants in Pediatric Venous Thromboembolism Treatment and Thromboprophylaxis: A Systematic Review of the Literature.

Venous thromboembolism (VTE) in children can lead to significant morbidity and mortality. Traditionally, treatment for thrombotic events in pediatric patients has been limited mainly to unfractionated heparin, low-molecular-weight heparin (LMWH), or vitamin K antagonists. Since the first non-vitamin K antagonist oral anticoagulant (NOAC) was approved for adult use, these agents have gained popularity for a variety of indications. This is largely due to their ease of administration, favorable pharmacokinetic and pharmacodynamic profile, decreased food interactions, and decreased need for therapeutic drug monitoring. Treating and preventing VTE with traditional anticoagulants in pediatric patients presents many challenges. This systematic review evaluated the current literature regarding pediatric NOAC trials. Additionally, based on an up-to-date query of clinicaltrials.gov, we detail current ongoing and as-yet unpublished clinical trials, study outcomes, and projected completion dates. Published pediatric NOAC trials have included 1,007 total children to date and have ranged from phase 1 to 4, with "indications" including both thromboembolism prophylaxis and VTE treatment. Three recent phase 3 trials, specifically involving rivaroxaban and dabigatran, have shown the agents to be at least as effective as traditional anticoagulants for acute and/or extended VTE treatment, with low frequency of recurrent thrombosis and clinically significant bleeding rates. Additionally, specially developed and tested pediatric formulations have allowed for accurate and reliable dosing, oral administration, stable pharmacokinetics and pharmacodynamics, and fewer drug or food interactions. Ongoing trials, anticipated for completion in the next few years, will reveal important information with regard to thromboembolism prophylaxis in special pediatric subpopulations and settings.

Management of Cepacia Syndrome With a Combination of Intravenous and Inhaled Antimicrobials in a Non-Cystic Fibrosis Pediatric Patient.

Burkholderia cepacia complex (Bcc) is an opportunistic pathogen, posing little risk to healthy individuals. The presentation of Bcc can vary from a virtually asymptomatic chronic infection, to an acute, life-threatening necrotizing pneumonia, acute respiratory distress syndrome, and bacteremia (cepacia syndrome) associated with a mortality rate up to 75%. We present the successful treatment of a 17-year-old male with chronic granulomatous disorder who presented with cepacia syndrome and confirmed Bcc pneumonia using a novel antimicrobial approach. Despite initial IV antimicrobial therapy, our patient continued to decline, developing hypotension requiring pressor support and eventually extracorporeal membrane oxygenation. An aggressive, multimechanistic approach including the combination of nebulized tobramycin, IV sulfamethoxazole-trimethoprim, ceftazidime, enteral minocycline, and corticosteroids was implemented. This multimechanistic antimicrobial approach in combination with systemic corticosteroids led to the successful treatment of cepacia syndrome in the setting of necrotizing pneumonia due to B cepacia with full respiratory recovery. We suggest that in patients with cepacia syndrome who continue to decline despite IV antimicrobial therapy, using multiple antimicrobial mechanisms of action may improve clinical outcomes.

Ceftaroline vs vancomycin for the treatment of acute pulmonary exacerbations in pediatric patients with cystic fibrosis.

INTRODUCTION: Respiratory infection with methicillin-resistant Staphylococcus aureus (MRSA) is an increasing complication in cystic fibrosis (CF) that results in accelerated lung function decline and mortality. Vancomycin is considered a first-line intravenous treatment agent for MRSA associated acute pulmonary exacerbations (APEs); however, rates of vancomycin intolerance and resistance have been observed. These factors have led to the exploration of additional treatment options for treating MRSA associated APEs. METHODS: This is a retrospective chart review conducted at a CF center including patients 0 to 21 years of age with CF admitted for an APE and treated with either vancomycin or ceftaroline between January 2016 and August 2018. The primary endpoint was to determine ceftaroline efficacy compared to vancomycin in the treatment of MRSA associated APEs. RESULTS: There were 180 patients included in the study with 90 patients in each antibiotic group. Admission to discharge forced expiratory volume in 1 second (FEV1 ) improved in the ceftaroline (66.5% vs 81.1%; P < .001) and vancomycin (65.5% vs 77.3%; P < .001) treatment groups. No difference existed in mean change in FEV1 (14.1% vs 13.5%; P = .25) or readmissions (15% vs 22; P = .27) between ceftaroline and vancomycin groups, respectively. DISCUSSION: In this retrospective study, no difference existed between ceftaroline and vancomycin with regard to observed improvement in lung function from admission to discharge. Additionally, no difference was observed in mean FEV1 or readmission rate between the two groups. Ceftaroline may represent an effective and safe intravenous antimicrobial option for targeting MRSA in pediatric CF patients with APEs.

Management of Paroxysmal Sympathetic Hyperactivity with Dexmedetomidine and Propranolol Following Traumatic Brain Injury in a Pediatric Patient.

We report a case of pharmacologic management of pediatric paroxysmal sympathetic hyperactivity (PSH) in a patient who experienced symptomatic resolution with dexmedetomidine and propranolol. Following a blunt traumatic subdural hematoma and diffuse axonal injury, an 8-year-old male developed PSH on approximately day 5 of the hospitalization. PSH symptoms identified in this patient were hyperthermia, tachycardia, posturing, and hypertension with associated elevations in intracranial pressure. Episodes of PSH continued to be observed despite appropriate titration of opiates, sedatives, and traditional blood pressure management. Dexmedetomidine and propranolol were subsequently initiated to attenuate acute episodes of PSH. A reduction in sedative requirements and improvement in symptoms followed, which facilitated successful extubation. The combination of propranolol and dexmedetomidine was followed by a decrease in the frequency and severity of acute episodes of PSH. After utilization of multiple treatment modalities to control PSH episodes in our patient, propranolol and dexmedetomidine may have helped attenuate PSH signs and symptoms.

Antihyperglycemic and Metabolic Effects of Ranolazine in Patients With Diabetes Mellitus.

The antianginal drug ranolazine, because of its unique mechanism of action, has been shown to have antihyperglycemic effects. Here, we review the reports on the antihyperglycemic and metabolic effects of ranolazine. MEDLINE was searched from 2000 to October 1, 2016 using the terms ranolazine, antihyperglycemic, diabetes, cardiology, and antianginal. Studies and reviews were included if they were in English and provided relevant data to inform practicing clinicians. Ranolazine has been shown to be effective as an antihyperglycemic while utilized as monotherapy or in combination with traditional diabetic regimens. A total of 6 studies were included in this review, with 5 being randomized controlled trials and 1 being a retrospective study. Of the 6 studies, 4 directly measured differences between baseline hemoglobin A1c (HbA1c), another measured endothelium function, and lastly the retrospective study evaluated outpatient clinic visit utilization, all-cause emergency department visits, inpatient admissions, and length of stay in a cohort of patients with angina and diabetes. In conclusion, ranolazine, because of its unique mechanism of action, may have a niche in therapy for patients with chronic stable angina pectoris and diabetes mellitus. Ranolazine has been shown to have positive antihyperglycemic and metabolic effects in patients with uncontrolled HbA1c.