Digoxin-specific Fab Antibody Fragments Research Articles

Recurrent digoxin overdose and treatment with digoxin-specific Fab antibody fragments

A case of overdose with digoxin on three separate occasions is presented. The patient received digoxin-specific Fab antibody fragments on each presentation without adverse effects. A discussion of digoxin toxicity and specific treatment follows. Immunologic aspects of therapy are emphasized.

Brain ouabain-like activity and the sympathoexcitatory and pressor effects of central sodium in rats.

Intracerebroventricularly infused hypertonic saline elicits sympathoexcitatory and pressor effects. To clarify the mechanisms mediating these effects, we evaluated blood pressure (BP), heart rate (HR), and renal sympathetic nerve activity (RSNA) responses to intracerebroventricular administration of 0.3 M NaCl, ouabain, and rat hypothalamic and pituitary extracts containing ouabain-like activity (OLA) in conscious Wistar rats, before and after intracerebroventricular preinjection of digoxin-specific antibody Fab (DAF) fragments. To exclude modulatory effects of arginine vasopressin (AVP), treatment with DAF fragments was in all experiments preceded by intravenous injection of the AVP antagonist [beta-mercapto-beta,beta-cyclopentamethylenepropionyl1,o- Me-Tyr2,Arg8]AVP. After AVP antagonist pretreatment, 0.3 M NaCl i.c.v. at 3.8 microliters/min for 10 minutes caused simultaneous increases in BP, RSNA, and HR. After AVP antagonist pretreatment, intracerebroventricular injections of 0.3 and 1.0 microgram/l microliter ouabain or the OLA equivalent to 1 microgram ouabain/2 microliters elicited similar significant increases in BP, HR, and RSNA. After pretreatment with AVP antagonist and DAF fragments (66 micrograms/4 microliters i.c.v.), BP, HR, and RSNA responses to 0.3 M NaCl, ouabain, and OLA were all significantly diminished. In contrast, combined AVP blockade and DAF fragments did not affect the BP response to intracerebroventricular angiotensin II, the BP, HR, and RSNA response to intracerebroventricular carbachol and to air stress, or the HR and RSNA responses to intravenous sodium nitroprusside. Intracerebroventricularly injected gamma-globulins (66 micrograms/4 microliters) did not affect the responses to 0.3 M NaCl, ouabain, or OLA.(ABSTRACT TRUNCATED AT 250 WORDS)

Digoxin-specific antibody Fab fragments in children

Digoxin-specific antibody Fab fragments in children

Digoxin Assay Anomalies Due to Digoxin-Specific FAB Immunotherapy

We demonstrate that digoxin-specific Fab antibody fragments, used in the treatment of severe digitalis intoxication, cause a marked interference with both fluorescence excitation transfer immunoassays and radioimmunoassays for digoxin. In addition, we describe a rapid ultrafiltration method that avoids the Fab-induced interference and affords excellent accuracy and precision. This technique will provide a useful adjunct to the clinical evaluation of patients with digoxin toxicity who are recipients of antidigoxin immunotherapy by enabling a precise determination of their serum digoxin concentrations. By separating the free and protein-bound digoxin this technique also may be useful in evaluating serum digoxin concentrations in patients with abnormal plasma protein concentrations.

Results of multicenter studies of digoxin-specific antibody fragments in managing digitalis intoxication in the pediatric population

Digitalis toxicity continues to be a problem for pediatric patients undergoing therapy with cardiac glycosides for heart failure or arrhythmias, as well as in accidental ingestions. In this article the previous use of digoxin-specific antibody Fab fragments to treat digitalis overdose or intoxication in children is reviewed. The case reports cited in the medical literature and the 57 pediatric cases gathered as a result of the multicenter clinical trial and postmarketing surveillance study reported here indicate that digoxin-specific antibody Fab fragments are effective in ameliorating signs of digitalis poisoning in children. Not only can Fab fragments rapidly eradicate potentially life-threatening arrhythmias and conduction defects, but they are also effective in treating hyperkalemia and other noncardiac manifestations of digitalis toxicity. In the small samples of patients studied to date, complications have been minimal and no allergic reactions to digoxin-specific Fab fragments have been observed. Recommendations for the management of digitalis intoxication in children are outlined.

Treatment of 150 cases of life-threatening digitalis intoxication with digoxin-specific Fab antibody fragments: Antman EM, Wenger TL, Butler VP, et al Circulation 81:1744–1752 Jun 1990

Treatment of 150 cases of life-threatening digitalis intoxication with digoxin-specific Fab antibody fragments: Antman EM, Wenger TL, Butler VP, et al Circulation 81:1744–1752 Jun 1990

Treatment of 150 cases of life-threatening digitalis intoxication with digoxin-specific Fab antibody fragments. Final report of a multicenter study.

One hundred fifty patients with potentially life-threatening digitalis toxicity were treated with digoxin-specific antibody fragments (Fab) purified from immunoglobulin G produced in sheep. The dose of Fab fragments was equal to the amount of digoxin or digitoxin in the patient's body as estimated from medical histories or determinations of serum digoxin or digitoxin concentrations. The youngest patient received Fab fragments within several hours of birth, and the oldest patient was 94 years old. Seventy-five patients (50%) were receiving long-term digitalis therapy, 15 (10%) had taken a large overdose of digitalis accidentally, and 59 (39%) had ingested an overdose of digitalis with suicidal intent. The clinical response to Fab was unspecified in two cases, leaving 148 patients who could be evaluated. One hundred nineteen patients (80%) had resolution of all signs and symptoms of digitalis toxicity, 14 (10%) improved, and 15 (10%) showed no response. After termination of the Fab infusion, the median time to initial response was 19 minutes, and 75% of the patients had some evidence of a response by 60 minutes. There were only 14 patients with adverse events considered to possibly or probably have been caused by Fab; the most common events were rapid development of hypokalemia and exacerbation of congestive heart failure. No allergic reactions were identified in response to Fab treatment. Of patients who experienced cardiac arrest as a manifestation of digitalis toxicity, 54% survived hospitalization.(ABSTRACT TRUNCATED AT 250 WORDS)

Near-fatal yew berry intoxication treated with external cardiac pacing and digoxin-specific FAB antibody fragments

The case of a 5-year-old girl who survived a near-fatal ingestion of yew plant leaves after treatment with CPR, transcutaneous pacing, and digoxin-specific FAB antibody fragments is presented. Multiple rhythm disturbances, including profound bradycardia, occurred. She required endotracheal intubation, external chest compressions, and application of a transcutaneous pacemaker. Paced cardiac contractions produced a dramatic improvement in her blood pressure and clinical condition. Two empiric injections of digoxin-specific FAB antibody fragments were administered, after which cardiac function and rhythm gradually improved. She was discharged in her normal state of health three days later. Yew leaves and berries contain several alkaloids that can produce fatal conduction disturbances. Transcutaneous cardiac pacemakers may be lifesaving for patients with transient cardiac toxicity from drug or toxin ingestions. In addition, cross-reactivity between digoxin-specific FAB antibodies and the alkaloids in the yew plant may exist and may have therapeutic importance, although this mechanism was unlikely to have helped our patient.

Fab fragments in the treatment of digoxin overdose: pediatric considerations.

Serious digoxin toxicity due to accidental or deliberate overdose is uncommon, but more than half of the cases reported in 1985 involved children. Toxicity can occur acutely, as with accidental overdose, or with long-term maintenance dosing. In children it is almost always acute. Conventional treatment includes gastric lavage or ipecac-induced emesis, and activated charcoal or nonabsorbable resins and cathartics to reduce absorption. Although children appear to tolerate massive ingestions without specific therapy, serum digoxin levels must be reduced quickly and safely when conventional measures have failed. Fab fragments of digoxin-specific antibodies have been successfully used to treat refractory digoxin toxicity. Indications for use should be limited to life-threatening digoxin toxicity when conventional therapy has failed.

Oleander tea: Herbal draught of death

A woman died after drinking herbal tea prepared from oleander (Nerium oleander) leaves. This case demonstrates the cross-reactivity between the cardiac glycosides in oleander and the digoxin radioimmunoassay. Digoxin-specific Fab antibody fragments have not been used in oleander poisoning, but these might prove to be lifesaving. Treatment of oleander toxicity is aimed at controlling arrhythmias and hyperkalemia; inactivation of the Na-K ATPase pump, however, can make treatment difficult.

Use of Fab fragments of digoxin-specific antibodies in the therapy of massive digoxin poisoning

A case of massive digoxin ingestion with multiple arrhythmias, consisting of high grade A-V block and ventricular ectopy not responsive to lidocaine, is described. The arrhythmias ceased following administration of digoxin-specific Fab fragments. The patient improved and was transferred to the psychiatric unit.

Treatment of life-threatening digitalis intoxication with digoxin-specific Fab antibody fragments: Smith TW, Butler VP, Haber E, et al N Engl J Med 307:1357–1362 Nov 1982

Treatment of life-threatening digitalis intoxication with digoxin-specific Fab antibody fragments: Smith TW, Butler VP, Haber E, et al N Engl J Med 307:1357–1362 Nov 1982

Treatment of life-threatening digitalis intoxication with digoxin-specific Fab antibody fragments: Smith TW, Butler VP, Haber E, et al N Engl J Med 307:1357–1362 Nov 1982

Treatment of life-threatening digitalis intoxication with digoxin-specific Fab antibody fragments: Smith TW, Butler VP, Haber E, et al N Engl J Med 307:1357–1362 Nov 1982

Fab Fragments of Digoxin-Specific Antibodies Used to Reverse Ventricular Fibrillation Induced by Digoxin Ingestion in a Child

Digitalis poisoning is a rare problem in children, but it may be life threatening. A case of massive overdose of digoxin in a 2 1/2-year-old boy that produced prolonged ventricular fibrillation refractory to conventional therapy is reported. After two hours the boy was given digoxin-specific Fab fragments of antibody in sufficient quantity to bind his estimated dose of 10 mg. By completion of the treatment minutes later, normal rhythm and circulation were restored. The serum free digoxin level before antibody administration was greater than 100 ng/ml, and it rapidly fell to undetectable levels after antibody was given. Digoxin bound to the antibody had a clearance half-life of approximately 48 hours. The child had no apparent neurologic damage and his intellectual function was normal on discharge. He had a transient hematuria and a residual incomplete right bundle branch block. Administration of purified Fab fragments of digoxin-specific antibodies can be life saving in children with digitalis poisoning, and prolonged cardiopulmonary resuscitation in children is justified when the cause of cardiac arrest is potentially reversible.

Massive Digoxin Poisoning Treated with Fab Fragments of Digoxin-Specific Antibodies

Acute digoxin poisoning is an uncommon but potentially lethal event in childhood. A case of massive digoxin ingestion and its successful treatment with Fab fragments of digoxin-specific antibodies is described.