Theophylline 175mg/5ml oral solution

Background: Apnea of prematurity affects at least 85% of infants born before 34 weeks' gestation and represents a significant clinical challenge in neonatal intensive care. Methylxanthines, including caffeine, theophylline, and aminophylline, have emerged as the primary pharmacological intervention for this condition. Objective: To conduct a comprehensive systematic review of the use of methylxanthine in the treatment and prevention of apnea episodes in preterm infants, evaluating efficacy, safety, and long-term outcomes. Methods: We searched multiple databases including PubMed, Embase, Web of Science for randomized controlled trials, retrospective studies, or case-control studies of methylxanthine effects in preterm apnea. Risk of bias was assessed using the Cochrane Risk of Bias tool. Results were summarized narratively and grouped by methylxanthine type, study design, and primary outcomes (reduction in frequency and severity of apnea episodes, success of extubation, risk of bronchopulmonary dysplasia). Results: Twenty-five studies (n = 4599 preterm infants) were included. The landmark Caffeine for Apnea of Prematurity (CAP) trial (n = 2006) demonstrated that caffeine therapy significantly reduced bronchopulmonary dysplasia (36.3% vs. 46.9%, adjusted OR 0.63) and facilitated the earlier discontinuation of positive airway pressure (median 1 week earlier). Studies with a smaller number of cases have consistently demonstrated the efficacy of methylxanthines in reducing the incidence of bronchopulmonary dysplasia and apneic episodes and in supporting successful extubation. Long-term follow-up at 11 years showed improved pulmonary function (FEV1 z-score -1.00 vs. -1.53). Discussion: Limitations of this review include heterogeneity in outcome definitions, small sample sizes in early studies, and the dominance of evidence from the CAP trial. Methylxanthines, particularly caffeine, are an evidence-based intervention used for apnea of prematurity, with demonstrated benefits that extend beyond reducing the frequency and severity of apnea episodes, including decreasing the risk of bronchopulmonary dysplasia as well as reducing the need for mechanical ventilation. No external funding was received for this review. No registration record exists for this systematic review.

Abstract licence: CC BY

IntroductionThe Clinical Toxicology Recommendations Collaborative was established by three international clinical toxicology societies and tasked to produce recommendations on the management of poisonings. The Activated Charcoal in Clinical Toxicology Workgroup (the Workgroup) was formed to provide recommendations on the administration of activated charcoal for gastrointestinal decontamination and enhanced elimination in poisoning.MethodsBased on a systematic review of the literature, 43 poisons or poison categories were selected for appraisal. Voting statements were drafted using a predetermined format. Strength of consensus was measured using the Disagreement Index as defined by the RAND/University of California at Los Angeles Appropriateness Method. A two-round modified Delphi method was used to reach expert consensus.ResultsThe Workgroup concluded that there is no role for activated charcoal in poisoning from arsenic, caesium, copper, ethanol, methanol, ethylene glycol, iron, lead, lithium, and metformin. Activated charcoal is appropriate after ingestion of antidysrhythmics (types I and III not discussed specifically), beta-adrenergic antagonists, bupropion, calcium-channel blockers, carbamazepine, cardiac glycosides, chloroquine, cocaine, colchicine, cyanide, dapsone, diphenhydramine, disopyramide, factor Xa inhibitors, ibuprofen, isoniazid, lamotrigine, methotrexate, moclobemide, opioids, organophosphorus insecticides, paracetamol (acetaminophen), paraquat, phenobarbital, phenytoin, quinidine and quinine, salicylates, selective serotonin reuptake inhibitors, sulfonylureas, thallium, theophylline, tricyclic antidepressants, valproic acid, venlafaxine, and warfarin. An additional dose of activated charcoal to complete gastrointestinal decontamination is appropriate after ingestion of carbamazepine, paracetamol, paraquat, phenobarbital, salicylates, thallium, theophylline, valproic acid and verapamil. The maximum time post-ingestion for which activated charcoal administration is recommended differs for each poison and different formulations. According to an individualized risk assessment, activated charcoal is appropriate up to 6 h post-ingestion for many poisons. If ongoing absorption is suspected, which may occur, for example, with pharmacobezoar formation, certain modified-release preparations, or when drug burden exceeds the limits of solubility, then activated charcoal can be administered beyond 6 h post-ingestion for gastrointestinal decontamination. Multiple-dose activated charcoal for enhanced elimination is appropriate in poisoning with carbamazepine, cardiac glycosides, colchicine, dapsone, phenobarbital, phenytoin, thallium and theophylline.Before deciding to perform endotracheal intubation to assist with the administration of activated charcoal, every clinician needs to weigh the potential complications and adverse effects of this procedure against the toxicity expected to be prevented by the administration of activated charcoal. This is a challenging decision, and a local poison centre and/or a bedside toxicology consultation can assist with this decision. Endotracheal intubation is not a benign procedure and is associated with a high rate of various adverse events, such as new haemodynamic instability, severe hypoxaemia, and cardiac arrest, which seem more common in children. In three studies that evaluated the risks of endotracheal intubation in over 2,200 poisoned patients, the rates of hypotension were between 1.5% and 11.8%, desaturation between 3.4% and 7.1%, and cardiac arrest in 0.4%. The risk of aspiration following administration of activated charcoal after endotracheal intubation is reported to be low (1-4%). Therefore, the decision to endotracheally intubate a patient to administer activated charcoal needs to carefully assess the patient's other comorbidities and the expected toxicity of the ingestion, which needs to be clinically significant to outweigh the risk of endotracheal intubation. Endotracheal intubation may also be considered if another treatment, such as haemodialysis or extracorporeal circulation, might be required or for transportation to another institution for ongoing clinical care. In these situations, for which endotracheal intubation has been performed for another indication, the risk-benefit will change in favour of activated charcoal administration. The following good practice statements were adopted to address the use of endotracheal intubation to facilitate the administration of activated charcoal. Endotracheal intubation should not be performed solely for the purpose of administration of activated charcoal in patients not anticipated to develop clinically significant complications of poisoning.In patients in whom endotracheal intubation is clinically indicated (e.g., compromised or unprotected airway, respiratory failure, significantly diminished level of consciousness, refractory seizures, hemodynamic instability), insertion of a nasogastric or orogastric tube is reasonable to facilitate gastrointestinal decontamination with activated charcoal.In patients with a clinically significant risk of developing life-threatening toxicity, endotracheal intubation is reasonable to safely facilitate gastrointestinal decontamination, especially if other treatment options are nonexistent or unavailable.Use of nasogastric or orogastric tube insertion without endotracheal intubation to facilitate the administration of activated charcoal: The following good practice statement was adopted: Nasogastric or orogastric tube insertion without endotracheal intubation should not be performed solely for the purpose of administration of AC.DiscussionThe decision to use activated charcoal is complex and depends primarily on the nature of the poison(s), the time since ingestion, the severity of the symptoms present at the time of decision or expected based on the dose ingested or patient comorbidities, and the availability of antidotes or other treatments. Although the existing level of evidence is primarily of low or very low quality, clinical decisions are still necessary.ConclusionsThe Workgroup recommends the administration of a single-dose of activated charcoal beyond the traditional 1 h post-ingestion time point in selected poisons and introduces the concept of an additional dose of activated charcoal to prevent further absorption of poisons that may remain in the gastrointestinal tract for prolonged periods of time. Multiple-dose activated charcoal is also recommended to enhance elimination in selected clinical scenarios.

Abstract licence: CC BY