Eran Geller

Transcatheter electrical shock ablation of ventricular tachycardia

Transcatheter shock ablation of ventricular tachycardia was attempted in seven patients who had drug-resistant ventricular tachycardia and in one patient in whom ventricular tachycardia was electrophysiologically induced during therapy with multiple antiarrhythmic drugs. Seven patients had previous myocardial infarction and five of them were high risk candidates for surgical therapy. One patient without organic heart disease had repetitive ventricular tachycardia manifesting two different patterns of left bundle branch block. After endocardial mapping, synchronized unipolar 250 to 300 J shocks (one to six) were delivered between the pole recording the earliest endocardial activity during ventricular tachycardia (40 to 200 ms before the onset of the QRS complex) and a body surface electrode. Immediate complications included severe but reversible cardiogenic shock (one patient), nonclinical ventricular tachycardia (two patients, requiring cardioversion in one), transient atrioventricular and intraventricular conduction disturbances (three patients) and permanent left bundle branch block (one patient). A late complication in one patient, left heart failure, occurred 3 days after delivery of five intracardiac shocks. In two patients, left ventricular ejection fraction markedly decreased and in one of them new ventricular contraction abnormalities appeared. Clinical ventricular tachycardia did not recur in five of the seven post-myocardial infarction patients after 7 to 17 months, and it was not inducible in the four patients undergoing late electrophysiologic study. In the patient with idiopathic ventricular tachycardia, one of the configurational types of ventricular tachycardia recurred.(ABSTRACT TRUNCATED AT 250 WORDS)

The respiratory effects of reversing midazolarn sedation with flumazenil in the presence or absence of narcotics

The purpose of this study was to determine the effects of reversal of sedation with flumazenil (F), in the presence or absence of opiates, on arterial oxygen saturation (Sao2) and cnd‐tidal CO2 (ETco2). Twenty‐four patients undergoing surgery and epidural anaesthesia were studied. Twelve patients (Group A) were orally premedicated with diazepam and 0.1 mg·kg‐1 morphine i.m. Intraoperative sedation consisted of midazolam 0.1 mg·kg‐1 and pethidine 0.7 mg·kg‐1 i.v. Twelve patients (Group B) were premedicated with diazepam and sedated intraoperatively with 0.1 mg·kg‐1 midazolam. In the recovery room, six patients in each group were randomly allocated to receive 1 mg of flumazenil while the others were allowed to awaken spontaneously (control). Sedation (eyes open vs closed), Sao2, ETco2, respiratory rate, blood pressure and pulse were non‐invasively monitored for 90 min. Administration of flumazenil resulted in a statistically significant increase in the number of patients with eyes open in both groups at 5 min, lasting 15 min in Group A and 30 min in Group B patients. An increase in Sao2 from 15–45 min after injection of flumazenil was observed only in Group B. No significant difference between groups in any other parameter was found. We concluded that reversal of benzodiazepine (BZ) sedation with flumazenil improved Sao2 in patients sedated with only BZ; in the presence of BZ and opiates, flumazenil did not affect respiratory parameters.

RO 15-1788 produces naloxone-reversible analgesia in the rat

Intraperitoneal and intracerebroventricular administration of the benzodiazepine antagonist RO 15-1788 produced analgesia to both thermal and mechanical pain. This effect was reversed by pretreatment with the opioid antagonist naloxone but was unaffected by pretreatment with the benzodiazepine agonist midazolam. Furthermore, administration of the benzodiazepine antagonist RO 15-3505 was without analgesic effect. It is, therefore, proposed that the intrinsic action induced by RO 15-1788 is exerted via the indirect activation of endogenous opioid systems and that the observed effect is not due to the action of the antagonist on the benzodiazepine receptor.

The use of flumazenil in the treatment of 34 intoxicated patients

The efficacy and safety of the newly available benzodiazepine (BDZ) antagonist flumazenil (Ro 15-1788, Anexate) was prospectively evaluated in the treatment of 34 intoxicated patients. Twenty-three patients had attempted suicide with various drugs, and 11 suffered iatrogenic BDZ overdose. Following 0.2 mg i.v. flumazenil (Flu) injection, 22 patients intoxicated mainly with BDZ (11 iatrogenic and 11 intentional) regained full consciousness within two minutes, enabling even extubation of two. Eight patients required repeated boluses or continuous infusion of Flu to maintain alertness. Five patients with mixed drug intoxication awakened only briefly and relapsed into unconsciousness. In spite of Flu doses of up to 20 mg, no effect on consciousness was observed in 7 patients, intoxicated mainly with non-BDZ drugs. No significant side effects were noted attributable to Flu which has proved to be a safe and effective drug. It may be employed to achieve complete reversal of pure BDZ overdose, or for unmasking the relative action of BDZ in mixed drug overdose. The danger of complications from drug overdose may thus be lessened, obviating the need for invasive interventions such as mechanical ventilation and invasive hemodynamic monitoring, at the same time decreasing risk and expense.

Epidural morphine pretreatment for postepisiotomy pain.

OBJECTIVE/DESIGNnA randomized double-blind controlled study was conducted on two groups of 45 parturients to evaluate the importance of the timing of epidural morphine administration for the relief of postepisiotomy pain. Both groups had preemptive analgesia by continuous lumbar epidural bupivacaine blockade. Upon completion of the episiotomy repair and before the onset of pain, the patients received epidural injections of 3 ml saline with or without 2 mg morphine in groups A and B respectively. When pain appeared, group A patients received an epidural injection of 3 ml saline while group B patients received 2 mg morphine in 3 ml saline. Postepisiotomy pain level was evaluated by a visual analogue scale.nnnRESULTSnThe incidence of pain in group B women following epidural morphine administration was 68.6%. This was significantly higher than that of group A at 15.6% (p < 0.01). Furthermore, group B showed that the rate of effective pain relief after 2 mg epidural morphine significantly decreases as the level of pain intensity rises (p < 0.01).nnnCONCLUSIONnEpidural morphine for postepisiotomy pain is much more effective if administered before the onset of pain.

Midazolam infusion and the benzodiazepine antagonist flumazenil for sedation of intensive care patients

ICU patients often require sedation. Midazolam (M), a new imidazobenzodiazepine, features rapid onset and rapid elimination time. Flumazenil (Ro 15-1788) is a new benzodiazepine antagonist. We studied the efficacy and safety of M by continuous infusion in 28 ICU patients: 16 post major surgery, and 12 medical patients, aged 20-77 years. M was administered as a loading dose of 0.05-0.15 mg/kg per min followed by continuous infusion of 0.05-0.1 mg/kg per h titrated to maintain patients asleep but arousable. M was administered for up to 14 days in doses of 1-15 mg/h and cumulative doses of up to 1915 mg. No untoward effects were noted except for slight decreases in blood pressure following the loading dose. ACTH challenge tests performed before and 24 h or more following the start of M showed no depression of adrenal responsivity. All patients meeting weaning criteria were weaned off mechanical ventilation while still on M. In 13 patients extubation was performed immediately after M was stopped, and flumazenil (0.38 +/- 0.27 mg, i.v.) given until full awakening. Patients remained awake yet calm. Vital signs remained stable after flumazenil. Midazolam by continuous infusion appears to be a safe and effective mode of sedation in ICU patients. Flumazenil may increase the flexibility and safety of this mode of sedation.

Early use of naloxone in shock — A clinical trial

Naloxone hydrochloride (N) 0.4-1.2 mg i.v. was administered during 10 episodes of shock (8 septic and 2 cardiogenic) in 9 adult patients. Shock was defined as systolic blood pressure (SBP) less than or equal to 90 mmHg and urine output less than 0.5 ml/h and signs and symptoms of hypoperfusion lasting for greater than or equal to 30 min, despite fluid loading to a CVP 5 cmH2O above baseline. N was given as early as 30 min after onset of shock and resulted in an increase of SBP from a mean of 75 +/- 10 to a mean of 130 +/- 25 mmHg maximum (P less than 0.01). Within 10-60 min urine output increased from 16 +/- 12 to 122 +/- 56 ml/h, heart rate, CVP and arterial blood gas tensions remained unchanged. No side effects were observed. Naloxone, even in small doses, may improve hemodynamic parameters in human shock, provided it is administered very early.

Early clinical experience in reversing benzodiazepine sedation with flumazenil after short procedures

Flumazenil (Flu) (Ro 15-1788, Anexate) is a newly synthetized specific benzodiazepine (BZD) antagonist which was recently introduced for clinical study. The drug was intravenously injected, in titrated doses, to patients undergoing diagnostic or therapeutic procedures in order to reverse the sedative effects of BZDs. A total of 63 patients undergoing hand surgery under i.v. regional block, lower abdominal surgery under epidural anesthesia, cardiac catheterization, intracardiac catheter ablation, cardioversion, gastroscopy and bronchoscopy were studied. Flu in a dose ranging from 0.1 to 0.42 mg effectively reversed BZD-induced sedation in all patients 1-2 min following i.v. injection. Patients were fully awake and oriented yet calm and in good mood. Flu was well tolerated even in the high risk cardiac patients, with no significant changes in vital signs nor any sign of local irritation at the site of Flu injection. No significant resedation was observed. Thus Flu was very useful in reversing BZD-induced sedation or unconsciousness in a variety of clinical situations.

Reversal agents in anaesthesia

Modern anaesthetic pharmacology makes it possible to provide relatively smooth, well controlled induction and maintenance of general anaesthesia. The process of recovery from anaesthesia however, remains one over which the anaesthetist has little control, as it depends on sometimes unpredictable drug interactions and on the individual patient’s usually unknown sensitivity to anaesthetic drugs. Ideally, a postoperative patient should be conscious, co-operative, calm and free of pain. This will provide better homeostasis of vital functions, allow early diagnosis and treatment of complications and decrease the need for nursing care. Unpleasant and even dangerous side effects, such as nausea, vomiting, shivering, etc. should be absent. The ability to safely reverse the effects of anaesthetics at will, may therefore enhance patient safety, reduce operating room turnover time, as well as lower recovery room staff workload. The search for safe and efTective antagonists of anaesthesia has a long and rather confusing history with the use of non-specific reversal drugs leading to unsatisfactory results. Todate, only two clinically useful specific antagonists exist: naloxone and the new benzodiazepine (BZD) receptor antagonist flumaaenil (Ro 15-1788). The present paper represents an attempt to delineate some of the published, as well as our own, experience with pharmacologic reversal of non-opiate sedatives and anaesthetic agents.

Transcatheter electrical shock ablation of a concealed accessory pathway

Transcatheter electrical shock ablation of a concealed posteroseptal accessory pathway was performed on a 57-year-old man with drug-refractory paroxysmal supraventricular tachycardia. A single 300-joules shock delivered at the ostium of the coronary sinus abolished conduction in the accessory pathway and resulted in long-term cure of the arrhythmia. No complications were observed during the procedure.