Theophylline Intoxication Research Articles

Comparison of different scores as predictors of mechanical ventilation and intensive care unit admission in acute theophylline poisoning.

Theophylline is commonly used to control respiratory diseases, especially in developing countries. Theophylline has a narrowed therapeutic index, and its toxicity is associated with morbidity and mortality. Physicians should be aware of the early prediction of the need for intensive care unit admission (ICU) and mechanical ventilation (MV). This study aimed to assess the power of the Rapid Emergency Medicine Score (REMS), Modified Early Warning Score (MEWS) and Simple Clinical Score (SCS) in predicting the need for ICU admission and/or MV in acute theophylline-poisoned patients. This cross-sectional study included 58 patients with acute theophylline poisoning who were admitted to our Poison Control Center from the 1st of July 2022 to the 31st of January 2023. The REMS, MEWS and SCS were calculated for all patients on arrival at the hospital. The area under the curve (AUC) and receiver operating characteristics were tested to compare scores. The median values of all studied scores were significantly high among patients who needed MV and/or ICU admission. The AUC of SCS was >0.9, with a sensitivity of 92.9% and specificity of 90.9% for the prediction of ICU admission. Meanwhile, MEWS was an excellent predictor of the need for MV (AUC=0.996, 95% CI=0.983-1.000). We recommend using SCS as an early predictor for ICU admission in acute theophylline-poisoned patients. However, MEWS could effectively predict MV requirements in acute theophylline-poisoned patients.

Epidemiological Survey of Theophylline Poisoning in a tertiary poison center

Background: Theophylline belongs to the category of bronchodilators and belongs to the family of methylxanthines. The purpose of this study was the epidemiological and clinical investigation of theophylline poisoning in patients admitted to Loghman Hakim Hospital in Tehran.
 Methods: This retrospective study reviewed the archived files of hospitalized patients from 2012 to 2022 by developing a questionnaire. All demographic information and results of examinations and laboratory tests were extracted from the files. The collected data were analyzed by SPSS version 25 software.
 Results: The age range of the patients was 3 months to 57 years. Out of 34 studied patients, 79.4% were female and 20.6% were male. The most common symptoms of poisoning were vomiting, nausea, sinus tachycardia, hyperglycemia and respiratory alkalosis. The incidence of hyperglycemia was 47.1%. One person had died.
 Conclusion: Poisoning with theophylline is uncommon and is mainly caused by self-harm. Except in severe poisonings, death and serious complications have not followed, and they have mostly recovered with supportive and symptomatic treatments.

A Case Report of Severe Theophylline Poisoning: Management and Review of Literature

Background Theophylline poisoning leads to multisystem toxicity. Management of theophylline overdose is focused on stabilizing cardiovascular manifestations of arrhythmia and hypotension, correcting metabolic derangements, aborting seizures and removing the drug from the system. We present a case of refractory seizures and haemodynamic instability from theophylline poisoning and reviewed the literature to update the management of severe theophylline overdose. Case Presentation A 73-year-old Chinese gentleman presenting with chills and rigor was admitted for management of sepsis. While admitted suffered seizures which were refractory to benzodiazepine and anti-epileptic drugs. Based on his previous admission for theophylline overdose, serum levels were done confirming severe theophylline poisoning. He was resuscitated and subsequently started on haemodialysis following which seizures were eventually aborted when theophylline levels were successfully reduced. Conclusion Severe theophylline poisoning should be identified early and appropriate treatment initiated promptly. In the management of refractory hypotension, methylene blue and venoarterial-extracorporeal membrane oxygenation are reasonable rescue therapies to consider. Multi-dose activated charcoal and extracorporeal treatments for elimination of drugs should be administered in severe theophylline poisoning.

The importance of hemodialysis in intoxications with 3 case reports

Introduction: While many intoxication cases are cured with medical treatment, antidote therapy and symptomatic treatment; some cases may need hemodialysis treatment or even invasive mechanical ventilation support. We aimed to examine the place of hemodialysis in three rare intoxication cases seen in our hospital.
 Case Reports: 43-year-old male patient was admitted to the emergency service with metformin intoxication . The patient with type B lactic acidosis was treated with urgent hemodialysis After a session of hemodialysis, the clinical and laboratory data returned to normal. 19-year-old female patient admitted to the emergency service with theophylline intoxication. The blood theophylline level was toxic.The patient with symptoms of intoxication (tachycardia, hypokalemia, severe nausea and vomiting, etc.) regressed after a session of hemodialysis . 22-year-old mental retarded male patient was admitted to the emergency service with loss of consciousness. The patient with metabolic acidosis was taken to the intensive care unit with coma of unknown cause. 4 sessions of hemodialysis was applied to the patient who developed acute renal failure. It was learned that the patient drank ethylene glycol (antifreeze).
 Result: All our patients could be discharged with full recovery.Hemodialysis treatment has an important place in the treatment of intoxication cases.

Troponine I versus Creatinine Kinase-MB as Predictor Markers of the Severity and Outcomes in Acute Theophylline Toxicity

Theophylline is a bronchodilator drug that is used in the treatment of asthma and chronic obstructive pulmonary diseases. Cardiovascular complications contribute to morbidity and mortality that associate acute theophylline intoxication. The current study aimed to investigate troponin I and creatine kinase-MB as predictors of the severity and outcomes in cases of acute theophylline intoxication. This prospective cohort study included thirty one patients with acute theophylline toxicity admitted to Tanta Poison Control Center during the period from the first of March 2018 to the end of February 2019. Patients were subjected to personal and toxicological history taking, vital signs collection, grading of acute theophylline toxicity and measurement of serum theophylline level. Both troponin I and creatine kinase-MB were measured at admission and 12 hours post admission. Results revealed that, troponin I at time of admission and 12 hours post admission in addition to creatine kinase-MB 12 hours post admission were significantly higher in cases with severe acute theophylline intoxication and patients who required intensive care unit admission. It was concluded that, troponin I could predict the severity and the requirement of intensive care unit admission in acute theophylline toxicity either with early or delayed presentation. On the other hand, creatine kinase-MB could be considered for patients with delayed presentation.

A fatal case of suspected unintentional theophylline intoxication

A fatal case of suspected unintentional theophylline intoxication

Extracorporeal treatment for theophylline poisoning: Systematic review and recommendations from the EXTRIP workgroup

Background. The Extracorporeal Treatments in Poisoning workgroup was created to provide evidence-based recommendations on the use of extracorporeal treatments (ECTRs) in poisoning. Here, the workgroup presents its systematic review and recommendations for theophylline. Methods. After a systematic review of the literature, a subgroup reviewed articles, extracted data, summarized findings, and proposed structured voting statements following a pre-determined format. A two-round modified Delphi method was chosen to reach a consensus on voting statements and the RAND/UCLA Appropriateness Method was used to quantify disagreement. Anonymous votes were compiled, returned, and discussed. A second vote determined the final recommendations. Results. 141 articles were included: 6 in vitro studies, 4 animal studies, 101 case reports/case series, 7 descriptive cohorts, 4 observational studies, and 19 pharmacokinetic studies, yielding a low-to-very-low quality of evidence for all recommendations. Data on 143 patients were reviewed, including 10 deaths. The workgroup concluded that theophylline is dialyzable (level of evidence = A) and made the following recommendations: ECTR is recommended in severe theophylline poisoning (1C). Specific recommendations for ECTR include a theophylline concentration [theophylline] > 100 mg/L (555 μmol/L) in acute exposure (1C), the presence of seizures (1D), life-threatening dysrhythmias (1D) or shock (1D), a rising [theophylline] despite optimal therapy (1D), and clinical deterioration despite optimal care (1D). In chronic poisoning, ECTR is suggested if [theophylline] > 60 mg/L (333 μmol/L) (2D) or if the [theophylline] > 50 mg/L (278 μmol/L) and the patient is either less than 6 months of age or older than 60 years of age (2D). ECTR is also suggested if gastrointestinal decontamination cannot be administered (2D). ECTR should be continued until clinical improvement is apparent or the [theophylline] is < 15 mg/L (83 μmol/L) (1D). Following the cessation of ECTR, patients should be closely monitored. Intermittent hemodialysis is the preferred method of ECTR (1C). If intermittent hemodialysis is unavailable, hemoperfusion (1C) or continuous renal replacement therapies may be considered (3D). Exchange transfusion is an adequate alternative to hemodialysis in neonates (2D). Multi-dose activated charcoal should be continued during ECTR (1D). Conclusion. Theophylline poisoning is amenable to ECTRs. The workgroup recommended extracorporeal removal in the case of severe theophylline poisoning.

A case report of acute theophylline intoxication, which caused potentially lethal arrhythmia, treated with direct hemoperfusion and continuous hemofiltration

A case report of acute theophylline intoxication, which caused potentially lethal arrhythmia, treated with direct hemoperfusion and continuous hemofiltration

Demographic and Clinical Characteristics of Theophylline Exposures between 1993 and 2011

Acute and chronic exposure to theophylline can cause serious signs and symptoms of poisoning. Additionally, with a narrow therapeutic range, toxicity could be observed even with therapeutic doses of theophylline. Epidemiological data on theophylline exposures in our country are extremely limited. The results of our study may improve the clinical management of theophylline poisoning in our country and elsewhere. To present aetiological and demographic features, clinical findings and treatment attempts with regard to theophylline exposures reported to Dokuz Eylül University Drug and Poison Information Center (DPIC), between 1993 and 2011. Descriptive study. The data regarding demographics, date, time, type of exposure, route of and reason for exposure, signs and symptoms upon admission, clinical management and outcome were retrospectively evaluated. The DPIC recorded 88,562 poisoning calls between 1993 and 2011; 354 (0.4%) of them were due to theophylline exposure. The mean age of all cases was 24.1±15.4 (range between 1 month and 90 years). Females dominated all age groups (72.6%, 257 females). Intentional exposure was significantly higher in women than in men (88.2% vs. 68.2% for all age groups; p<0.001 for children; p<0.001 for adults; p<0.001 for all age groups). While 60.5% of the cases had no symptoms, severe signs of toxicity were present in 1.9% of theophylline exposure cases during the telephone inquiry. Signs and symptoms were found to be significantly more prevalent in adults than in children (p<0.01). The serum theophylline level was regarded as toxic in 74% (65 toxic levels) of theophylline measured cases. Clinical signs and symptoms were found to be significantly prevalent in cases with toxic theophylline levels (p<0.001). The rate of gastrointestinal decontamination procedures was higher than that of recommended gastrointestinal decontamination procedures by DPIC (83% and 66%, respectively). There were two fatalities (4.6%) associated with chronic theophylline toxicity and theophylline overdose in an acute setting for suicide (a 90 year-old and 25 year-old, respectively). Although most of the theophylline exposure cases had no symptoms, some reported serious signs and symptoms of poisoning such as hypokalaemia, tachycardia and hyperglycaemia. DPICs have an important role in the management of theophylline exposure without unnecessary gastrointestinal decontamination procedures.

Lethal poisoning with theophylline in the form of rectally administered tablets.

The paper discusses the case of death of a 56-year-old man who died in a municipal hospital from which his body was taken to the Chair and Department of Forensic Medicine, Jagiellonian University Medical College, Krakow. The man was said to have been found unconscious by accidental passers-by. While being transported to the hospital's emergency department, he suffered an attack of convulsions and went into cardiac arrest. He was subsequently successfully resuscitated. A physical examination performed at the hospital revealed the presence of multiple, only slightly dissolved tablets in the man's rectum. The patient died on the 25th day of hospitalization. A toxicological analysis showed a toxic concentration of theophylline (25 mg/l) in the man's blood. Theophylline was identified as the main ingredient of the tablets. The cause of death was thus given as theophylline poisoning. The reported case is unusual in that the poisoning occurred as a result of overdosing on an oral drug which was administered by the victim rectally, and in that the chosen substance currently is not very commonly used in medicine, and does not cause symptoms of intoxication.

Whole-Bowel Irrigation As Adjunctive Treatment For Sustained-release Theophylline Poisoning: A Case Report

Whole-Bowel Irrigation As Adjunctive Treatment For Sustained-release Theophylline Poisoning: A Case Report

Successful treatment of life threatening theophylline intoxication in a pregnant patient by hemodialysis

High-flux hemodialysis is the extracorporeal treatment of choice for various life threatening intoxications. Most published reports support the use of hemoperfusion in the context of severe theophylline poisoning, but the technique is limited by its significant side-effects. We present a potentially life threatening theophylline overdose treated with hemodialysis in a pregnant patient. For the first time the amount of theophylline removed was measured in the total collected spent dialysate, after a 3.75 hour hemodialysis and an 8 hour extended dialysis.

Relation between Theophylline Serum Level with ECG Changes and Poison Severity Score (PSS) Among Some Theophylline Intoxicated Patients in Menofia Poison Control Center (MPCC) A Prospective Study

There are numerous toxins and drugs that can cause, in overdose, ECG changes, even in patients without history of cardiac pathology. Theophylline intoxication results in substantial morbidity and mortality, particularly in those with chronic overmedication. The aim of this work was to study ECG changes in cases of poisoning by theophylline overdose that were admitted to MPCC over 2011 and the relation between ECG changes, theophylline blood level and poison severity score. In this study, theophylline overdose patients admitted to MPCC in the period from 1st of January 2011 to 31st of December 2011 were included. The total patients' number was 44 patients. Most cases of the study were females (77.2%) in the age group of (20-<40) years (40.9%), mainly from rural side (65.9%). Regarding relation between theophylline serum level and clinical manifestations, a significant relation was found between serum level and each of vomiting and dizziness, where both were noticed with majority of cases of minimal and moderate toxicity serum level. Regarding poison severity score, exactly one half of moderate and severe cases had minimal toxicity serum level, and the other half had moderate toxicity level. A significant negative correlation between theophylline serum level and PCO2 was found. There was a non significant negative correlation between theophylline serum level and each of Na and K blood level. Concerning ECG changes, a significant relation was found between theophylline serum level and each of sinus tachycardia and second degree heart block.

Theophylline Intoxication During Anesthesia: A Case Report and Literature Review

Theophylline Intoxication During Anesthesia: A Case Report and Literature Review

Acute Theophylline Intoxication in Some Egyptian Children and Adolescents : A Prospective Study

Acute Theophylline Intoxication in Some Egyptian Children and Adolescents : A Prospective Study

Selective bilateral hippocampal lesions after theophylline-induced status epilepticus causes a permanent amnesic syndrome

Theophylline is known to increase the risk of epileptic seizures and might have a role in seizure-induced brain damage. We present a 55-year-old man who developed an amnesic syndrome after status epilepticus, caused by accidental theophylline intoxication. Imaging studies revealed acute, selective bilateral hippocampal damage, which corresponded to severe disturbances in bilateral temporal functions on neuropsychological testing. Three months later, the memory deficits persisted, while imaging exhibited bilateral atrophy of the hippocampus. Upon his long-term, 18-month follow-up, the patient demonstrated improvements in his daily living abilities, despite the persistence of bilateral temporal deficits. This report provides evidence that theophylline has the potential to provoke permanent seizure-induced neural damage, presumably via inhibition of adenosine receptors, and especially in vulnerable regions of the brain, such as the hippocampus.

Overdose of methyldopa, indapamide and theophylline resulting in prolonged hypotension, marked diuresis and hypokalaemia in an elderly patient

An 89-year-old man with a history of hypertension, chronic obstructive pulmonary disease, personality disorder and previous attempts of self-poisoning attempted suicide by swallowing two mouthfuls of tablets (methyldopa 250 mg, theophylline SR 200 mg, indapamide 2.5 mg and paracetamol 500 mg). He had prolonged, severe hypotension, necessitating the use of 3000 ml of Gelofusine and almost 2 days of intravenous norepinephrine infusion. He had marked diuresis for 4.5 days, requiring continuous and bolus infusions of intravenous fluids. He had marked renal potassium loss, requiring vigorous potassium replacement therapy. Multiple-dose activated charcoal was used to enhance theophylline elimination. The plasma paracetamol level was below the treatment line. Methyldopa via its metabolite stimulates postsynaptic alpha-adrenergic receptors in cardiovascular control centres in the brain, causing a reduction in peripheral sympathetic tone and a fall in arterial blood pressure and heart rate. In overdose, it causes hypotension, bradycardia and drowsiness. The natriuretic, kaliuretic and vasodilatory effects of indapamide are exaggerated in overdose, resulting in diuresis, hypokalaemia and hypotension. Theophylline markedly increases the level of circulating catecholamines, which stimulate the vascular beta(2)-adrenergic receptors with decreased peripheral vascular resistance. Peripheral vasodilation and hypotension occur in significant theophylline poisoning. Intracellular shift of potassium results in hypokalaemia. The prescribing physicians should recognise elderly patients at a high risk of self-poisoning and avoid using drugs with a high toxicity in overdose (e.g. theophylline and methyldopa). Restricting access to hazardous drugs (in overdose) would be of paramount importance to reduce the number of severe acute poisoning cases and case-fatalities.

Positive effect of N-acetylcysteine in theophylline intoxication

Positive effect of N-acetylcysteine in theophylline intoxication

Severe theophylline intoxication: a delay in charcoal haemoperfusion solved by oral activated charcoal

Severe theophylline intoxication: a delay in charcoal haemoperfusion solved by oral activated charcoal

急性テオフィリン中毒に対し血液吸着と血液透析を行い改善した１例

急性テオフィリン中毒に対し血液吸着と血液透析を行い改善した１例