General Anesthetic Management of a Patient With Hypertrophic Cardiomyopathy for Oral Surgery: Did Digitalis Contribute to Bradycardia?

Stabilization of circulatory dynamics is a critical issue in the anesthetic management of patients with hypertrophic cardiomyopathy (HCM). In this report, we managed general anesthesia for a 74-year-old male patient with nonobstructive HCM who developed circulatory instability intraoperatively. Severe bradycardia measuring 35 beats/min and hypotension measuring 78 mm Hg systolic were observed during surgery. Using stroke volume variation and stroke volume from the FloTrac as indices, successful circulatory management was performed with dopamine. The hypotension and bradycardia were thought to be the result of methyldigoxin and possibly associated with our perioperative management. Cardiology consult should have been obtained. We demonstrated that the FloTrac can be beneficial in diagnosing and managing cardiovascular instability and administration of dopamine in the anesthetic management of nonobstructive HCM patients.

[Therapeutic drug monitoring in perioperative period--management of atrial fibrillation in a patient with bradycardia due to relative overdose of digitalis].

We reported a 79 year old man with preoperative bradycardia due to relative overdose of digitalis prior to undergoing subtotal gastrectomy. The patient had received metildigoxin 0.2 mg.day-1 for atrial fibrillation preoperatively and severe bradycardia of 35-41 bpm was found on the preoperative ECG examination. Serum digoxin level was detected to be 1.91 ng.ml-1 on the day before surgery. We thought this serum level must be toxic for him, even though it was within normal limits for the majority. As we thought that his bradycardia had been caused by relative overdose of digitalis, he was withheld to receive metildigoxin on the day before surgery and thereafter. Heart rate on arrival at the operating theater was around 40-45 bpm, and therefore the patient was placed on a temporary pacemaker catheter before the anesthetic induction to prevent aggravating bradycardia during anesthesia and surgery. Heart rate during procedure was 50-70 bpm and hemodynamics was stable. Intravenous digoxin was restarted on the 2nd postoperative day because of decrease in serum digoxin level to 0.84 ng.ml-1 and it was converted to metildigoxin 0.1 mg.day-1 when he was permitted to take pills per os. Our experience demonstrates that perioperative therapeutic drug monitoring is clinically important for anesthesiologists to make proper pharmacological management of surgical patients who have received digitalis.

Adverse drug reactions resulting in hospital admission.

A 14-month (1992/3) prospective study was performed in two departments of the University Hospital Centre (UHC) in Zagreb. The aim of the study was to assess the rate of drug-related hospitalizations, drugs that caused adverse drug reactions (ADRs), and all factors which could have been of importance for their appearance. One hundred and thirty (2.5%) of 5,227 patients were admitted to hospital because of ADRs. The most frequently ADR-related drugs were nonsteroidal anti-inflammatory drugs and analgesics (64.6%). They were followed by cardiovascular agents (20.8%) and antimicrobials (3.8%). Acetylsalicylic acid (aspirin) caused 38.5% of hospital admissions, other nonsteroidal anti-inflammatory drugs (NSAIDs) 23.1% and medigoxin 15.4% of hospitalizations. The most frequent ADRs were upper gastro-intestinal tract bleeding (64.6%), cardiac rhythm disturbances (13.9%), blood cell disorders (4.6%) and hypoglycemia (2.3%). Regarding the patients' age, 52.3% of patients was younger and 47.7% older than 65. Sixty-one point five percent of patients was taking more than one drug, older patients (48 patients--77.4%) have been taking a significantly higher number of drugs than the younger (32 patients--47.1%) (p < 0.0001) ones. Drug interactions caused 23.8% of ADRs. Only 11 (8.5%) of patients suspected themselves that the drug might have caused the ADR. Improvement was observed in the majority of patients (65.4%), 25.4% recovered completely, 4 (3.0%) died in the hospital because of ADRs. 3.0% of patients as well died of their underlying diseases, 2.3% were transferred to other departments for their underlying diseases, and one patient left the hospital on his free will.

[Digoxin-like immunoreactivity in newborn infants--a pitfall of digoxin therapy?]. / Digoxin-ähnliche Immunoreaktivität bei Neugeborenen--eine Falle bei der Digoxintherapie?

Endogenous digoxin-like immunoreactive substances (DLIS) show crossreactions with different immunoassays used for digoxin drug monitoring. In 61 blood samples of 47 eutrophic healthy newborns with jaundice, digoxin serum concentrations were measured during examination of serum bilirubin using a digoxin polarisation immunoassay. Although there was no digoxin therapy in any case, we found positive serum digoxin immunoreactivity (> or = 0.2 ng/ml) in 86% of serum samples. The mean DLIS-concentration was 0.43 +/- 0.19 ng/ml with a maximum of 0.9 ng/ml. We found a significant indirect correlation (rs = -0.34; p = 0.05) between age and serum DLIS concentration. A case report demonstrates the possibility of DLIS interference on digoxin drug monitoring.

[Serum digoxin in children treated with beta methyl digoxin]. / Concentraciones séricas de digoxina en niños tratados con beta metil digoxina.

Concentrations of serum digoxin were measured by the polarized immunofluorescence Abbot TDx11 method in 59 samples from 53 children under treatment with mean beta methyl digoxin doses of 8.9 +/- 2.0 micrograms.kg.day. The therapeutic range for serum digoxin concentration was estimated to be 0.9 to 2.25 ng/ml. Simultaneous Na, K and creatine serum concentrations were measured. In 36 samples mean serum digoxin level was 1.52 +/- 0.45 ng/ml -within therapeutic range- and in only one of these cases clinical evidence of toxicity was apparent. In 15 samples digoxin level was above the therapeutic range and 11 patients of this group (73%) showed clinical signs of toxicity, consisting in arrythmias (six cases: supraventricular in 5 patients, ventricular in one child) and gastrointestinal symptoms (eight patients). Six patients with digoxin levels over therapeutic range and signs of digitalis toxicity had coincidental acute renal failure, which in 4 cases was subclinical--in 2 of these late it was pre-renal- and, in spite of this, all were inadvertently given the usual dosage of beta methyl digoxin. Almost invariably there was clinical evidence of toxicity when digoxin serum levels were above 2.4 ng/ml, so established maximal therapeutic level at 2.25 ng/ml seems adequate. Signs of digitalis toxicity must be looked on systematically in children treated with such drugs. In the critically ill or in children with acute renal failure it is necessary to monitor serum digoxin concentration. Among the clinical signs of toxicity, gastrointestinal symptoms are more frequent in children. An oral dose from 7 to 10 micrograms.kg.day of beta methyl digoxin in recommended.

Serum digoxin and beta-methyldigoxin in elderly patients on hospital admission: correlation with home compliance and clinical variables.

Serum digoxin and beta-methyldigoxin (BMD) were measured in 165 elderly patients (age greater than 60 years) admitted to hospital, of whom 109 had been treated at home with digoxin and 56 with BMD. The mean BMD level was significantly lower than that of digoxin (1.1 vs. 1.4 ng/ml). Creatinine clearance and daily dose were the variables most strongly associated with digoxin level, and the prescribed dose and serum albumin were the best predictors of the BMD concentration. Compliance was assessed by a compliance index (CI), namely the ratio of the measured glycoside concentration, corrected for creatinine clearance, over the expected steady-state dose, calculated from a hospitalized reference group. Compliant individuals in both treatment groups, i.e. those with a CI greater than the median value, were characterized by a lower daily dose and dosage frequency. Toxicity, whether clinical or electrocardiographic, was present in 9% of the patients and was associated only with a significantly higher mean serum level of the drug.

[Pharmacological and clinical research on the interaction of digitalis and amiodarone in heart disease patients with varying degrees of cardiac insufficiency]. / Ricerca farmacologico-clinica sull'interazione digitale-amiodarone in pazienti cardiopatici con insufficienza cardiaca di vario grado.

The increasing use of amiodarone as antiarrhythmic drug has raised the possibilities of dangerous effects from amiodarone-digitalis interaction. We have studied twelve patients who were taking digitalis and to whom amiodarone was administered because of arrhythmias. We found a 75,42% increase of digitalis plasma levels (p less than 0,001) in the early days of amiodarone therapy, and a 52,1% increase (p less than 0,001) in the medium term. An inverse correlation was found (r = -0,65; p less than 0,05) between the plasma levels of digitalis during the steady-state control period and during the following 2-to-6 months evaluation. Acute episodes of cardiac failure caused in our patients an abrupt increase of digitalis plasma levels: in three patients digitalis toxicity occurred. Based on our experience, we recommend that the dose of digitalis be halved when the two drugs are given together in patients with various degree of cardiac failure; moreover digitalis plasma levels should be frequently monitored in these patients. On the other hand digitalis administered according to age, sex, weight, kidney function, together with amiodarone, can be given at full dosage in patients without cardiac failure.

[Disorders of the ability to distinguish colors during digitalis therapy (author's transl)]. / Störungen des Farbunterscheidungs- vermögens unter Digitalistherapie.

31 hospitalized patients treated with beta-methyl digoxin and 34 treated with beta-acetyl digoxin were examined for color vision disturbances and compared with a control group (n = 17). The serum digoxin concentration was determined radioimmunologically. A significant correlation (p less than 0,01) was found between the severeness of the disturbances in color vision and the concentration of digoxin in the serum. The disturbances concerned different wave length regions. The lapse of time for disturbances in the distinguishing colors is being described in a case of suicidal intoxication.

Effect of metildigoxin (beta-methyldigoxin) on congestive heart failure as evaluated by multiclinical double blind study.

The efficacy on congestive heart failure of metildigoxin (beta-methyldigoxin, MD), a derivative of digoxin (DX), which had a good absorption rate from digestive tract, was examined in a double blind study using a gorup comparison method. After achieving digitalization with oral MD or intravenous deslanoside in the non-blind manner, maintenance treatment was initiated and the effects of orally administered MD and DX were compared. MD was administered in 44 cases, DX in 42. The usefulness of the drug was evaluated after 2 weeks, taking into account the condition of the patient and the case of administration. No significant difference was observed between the usefulness of MD and that of DX. The use of digitalis differs according to the preparation involved. In the double blind study on MD and DX, the way in which digitalis was used may have inclined towards the way in which DX, which is more familiar to us, is used. Therefore, even if MD were superior to DX in usefulness, it would be difficult to obtain a result which proved this. Taking these points into consideration, it is concluded that MD is practically useful in clinical medicine.