Severe Theophylline Intoxication Research Articles

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.

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.

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.

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

Treatment of Theophylline Poisoning

In Reply.— We appreciate the comments of Strauss and Modanlou on the role of multiple-dose activated charcoal in the treatment of infants with severe theophylline intoxication. We are aware of both studies which they have published in this area and have also used multiple-dose charcoal in neonates.1-3 The infant in our case report was not considered a candidate for multiple-dose activated charcoal because of the absence of bowel sounds. He was also not a candidate for hemodialysis or hemoperfusion because of problems with vascular access which resulted from his complex congenital heart disease (including inferior vena cava occlusion and inaccessible subclavian veins).

Fatal theophylline poisoning with rhabdomyolysis

A fatal case of theophylline poisoning is described. The patient developed rhabdomyolysis, renal failure and compartment syndrome, as well as the more usual features of severe theophylline poisoning. Dantrolene appeared to be useful in controlling the hypermetabolic state associated with the overdose and may have a role in future treatment.

T Wave Inversion Associated with Severe Theophylline Toxicity

Adverse cardiovascular effects are commonly seen in severe theophylline poisoning. Primary ST-T wave changes have not been described previously. We report T wave inversion associated with severe theophylline toxicity in a 33-year-old woman with no evidence of organic heart disease. The T wave inversion resolved after treatment. Physicians should be alerted to possible T wave abnormalities in patients with severe theophylline poisoning.

Self‐poisoning with Theophylline

A heavy smoking male patient with moderate to severe theophylline poisoning is presented. Repeated doses of oral charcoal were given in addition to usual supportive treatment. During this treatment the elimination half-life of the drug (T1/2) was 2 hours. The toxic symptoms disappeared rapidly when the serum concentration was reduced to the therapeutic concentration range. T1/2 was approximately 24 hours in the same patient in a steady state study without oral charcoal treatment. Repeated doses of oral charcoal seem to increase theophylline elimination and should be administered in moderate to severe theophylline poisoning in addition to the usual supportive treatment and correction of metabolic disturbances.

Increased activity of creatine kinase isoenzyme MB in a theophylline-intoxicated patient.

A 78-year-old woman had increased activities of creatine kinase (CK; EC 2.7.3.2) and CK-MB isoenzyme in her serum, associated with severe theophylline intoxication. The time course for CK-MB activity was similar to that from an acute myocardial infarction. Clinical findings, however, including electrocardiograms, did not support the diagnosis of myocardial infarction. We suggest caution in interpreting CK-MB results in severe theophylline intoxication.

Cardiovascular effects of toxic concentrations of theophylline in the dog

A canine model of theophylline toxicity was used to study the cardiovascular effects seen in severe theophylline poisoning. Eight mongrel dogs were divided equally into two groups. The dogs were anesthetized with pentobarbital and paralyzed with pancuronium bromide. They were ventilated with 100% oxygen and underwent the placement of pulmonary arterial, central venous, femoral arterial, and peripheral venous lines. Group 1 animals received 5.6 mL/kg D5W intravenously (IV) over 20 minutes. Group 2 animals received 140 mg/kg (5.6 mL/kg) of aminophylline IV over the same period. Peak theophylline levels in Group 2 animals averaged 208.9 micrograms/mL. Group 2 animals suffered a marked fall in mean arterial pressure (MAP) and an increase in heart rate. In spite of the fall in MAP (P less than .01), cardiac index actually was increased almost two-fold over Group 1 animals, due mainly to a fall in systemic vascular resistance index (P less than .01). There were no physiologically significant differences in ventricular filling pressures or stroke index between the two groups.

Fatal overdose from a sustained-release theophylline preparation

A 26-year-old woman ingested approximately 9 g of theophylline (Theodur). She exhibited agitation, generalized seizures, hyperglycemia, hypokalemia, hypomagnesemia, hypophosphatemia, and diuresis. Later in her hospital course rhabdomyolysis, myoglobinuria, and acute renal failure occurred. Hemodialysis was performed to correct electrolyte imbalance. She subsequently died of intractable shock and hyperkalemia. This case illustrates the metabolic abnormalities which may occur with severe theophylline intoxication.

Hemoperfusion in Theophylline Neurotoxicity

Four patients with severe theophylline toxicity (theophylline levels of 60 to 180 micrograms/ml) are reported. Three patients with neurotoxicity were treated with hemoperfusion. Two of these were hemoperfused early after the onset of seizures; they recovered with no neurologic deficit. In the third patient hemoperfusion was delayed for 16 hours after uncontrolled seizures; severe brain damage resulted. The fourth patient, who had the highest peak theophylline level but no seizures, was successfully treated with conservative management and peritoneal dialysis. The role of hemoperfusion in severe theophylline intoxication is discussed.

Pharmacokinetics of Severe Theophylline Intoxication Managed by Peritoneal Dialysis

In a patient severely poisoned with theophylline, saturation kinetics were demonstrated at serum concentrations > 35 micrograms/ml with subsequent conversion to first order kinetics (t 1/2 = 5.4 h). Peritoneal dialysis was used to enhance the drug's removal. The mean theophylline clearance was greater for dialysate (5.11 ml/min) than for urine (1.98 ml/min) or gastric fluid (0.32 ml/min). Urinary elimination occurred as a constant first order process (t 1/2 = 4.3 h). Peritoneal dialysis is a valuable early adjunct in the management of severe theophylline intoxication.