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Biomedical subjects

P Halpern

Publications and source records attributed to P Halpern.

17 recordsLinked to original sources
PubMed1992

The effects of halothane, enflurane and isoflurane on the isolated rat heart recovering from cardioplegic arrest.

The direct cardiac effects of volatile anesthetics following cardioplegic ischemia were investigated in isolated, paced rat hearts. In one series of experiments, the hearts were perfused with oxygenated Krebs Henseleit solution for a 15-minute stabilization period and then the effect of the volatile anesthetic was tested. In another series of experiments, after the stabilization period, the hearts were subjected to cardioplegic (KCl 20mEq/L) ischemia at 30 degrees C for 30 minutes and then the effect of the volatile anesthetic was tested. Halothane, enflurane or isoflurane was introduced to the Krebs Henseleit solution at 0.7 and 1.4 minimal alveolar concentration. All the volatile anesthetics decreased myocardial contractility in a dose dependent manner both before and after cardioplegic arrest. Halothane decreased coronary flow, while isoflurane and enflurane increased coronary flow in both the cardioplegic and non-cardioplegic hearts. The influence of the anesthetics was transient and ceased once they were withdrawn. Ischemic cardioplegia did not affect the response to volatile anesthetics.

Animals↗
PubMed1991

The use of flumazenil in the management of acute drug poisoning--a review.

The popularity and widespread availability of benzodiazepines (BZD) has led to their frequent abuse in intentional drug poisoning. Although mortality from pure BZD overdose is usually small, in elderly, debilitated patients, or when BZD are combined with other CNS depressant drugs, morbidity increases significantly and outcome may be fatal. Drug overdose is therefore a medical emergency necessitating close observation and support of vital functions. Recently, the specific BZD antagonist flumazenil (Anexate) has become clinically available and much experience in its usefulness has accumulated. The present review summarizes a total of 30 studies and reports published to date, involving approximately 760 intoxicated patients. Flumazenil was evaluated both in prehospital use as well as in emergency rooms or in intensive care units. The age of patients ranged from 4-90 years and doses of flumazenil varied between 0.3-10 mg, approximately 1 mg being the most frequently used. All patients intoxicated with only BZD returned to full consciousness within minutes after the injection of flumazenil. When a mixture of BZD and other CNS depressants was abused, a range of effects was observed. This varied from no change to a return to full orientation, depending on the contribution of the BZD to the state of unconsciousness. Re-sedation occurred in about 65% of flumazenil treated patients, usually within 0.5-3 h after the first dose, the shorter interval being associated with mixed-drug poisoning. Repeated doses of the antagonist (0.2-2 mg), sometimes followed by continuous infusion (0.1-0.5 mg/h), were effective in maintaining patients fully oriented.(ABSTRACT TRUNCATED AT 250 WORDS)

Anti-Anxiety Agents↗
PubMed1991

Hyperbaric oxygen therapy for ischaemia of the hand due to intra-arterial injection of methadone and flunitrazepam.

We present a case of accidental injection of oral methadone and flunitrazepam into the ulnar artery, with resultant severe ischaemia of the hand. Initial therapy consisted of systemic vasodilators, low molecular weight dextran and aspirin. When this therapy failed to produce improvement and amputation of the involved hand seemed inevitable, the patient was referred for hyperbaric oxygen (HBO) therapy. In spite of a 12 day delay in the initiation of HBO, the response was dramatic, with almost complete resolution of the ischaemic signs and symptoms. Intra-arterial injection, which is only rarely encountered in drug addicts, frequently results in severe ischaemia of an extremity, and carries with it a poor prognosis with currently accepted therapy. Given the presently reported experience and the known physiology of HBO, we conclude that HBO should be started early in the treatment of intra-arterial injection of drugs, and should also be considered following prolonged delays.

Adult↗
PubMed1991

Cardiorespiratory effects of antagonism of diazepam sedation with flumazenil in patients with cardiac disease.

The specific benzodiazepine antagonist flumazenil is currently under intense study. Despite much clinical experience, no detailed invasive hemodynamic studies of its use in cardiac patients have been published. In the present study, hemodynamic and respiratory variables were measured in 10 cardiac patients undergoing catheterization of the right and left sides of the heart, before and after sedation with intravenous diazepam, and after reversal of sedation with flumazenil. A sleep dose of diazepam (12.2 +/- 5.1 mg, mean +/- SD) caused only slight decreases in mean arterial pressure (103 +/- 12 to 98 +/- 14 mm Hg; P less than 0.05), pulmonary capillary wedge pressure (13.2 +/- 6.3 to 11.7 +/- 6.6 mm Hg; P less than 0.05), and left ventricular end-diastolic pressure (20.8 +/- 7.5 to 17.3 +/- 10.0 mm Hg; P less than 0.05), with no significant changes in respiratory gas homeostasis. Intravenous flumazenil (0.22 +/- 0.07 mg) resulted in spontaneous awakening and return to full orientation, yet caused no significant alteration in either hemodynamic or respiratory variables measured. Reversal of diazepam-induced sedation by flumazenil in cardiac patients appears safe and effective.

Aged↗
PubMed1989

A benzodiazepine receptor antagonist improves emergence of mice from halothane anaesthesia.

The benzodiazepine receptor antagonist, flumazenil, at a dose of 10 mg/kg given intraperitoneally to mice, had no effect on the minimum air concentration (MAC-50) of halothane causing anesthesia in 50% of the animals and which was 1.0% by volume of the inhaled air. Diazepam, 10 mg/kg, potentiated the effect of halothane. When the mice had been pretreated with diazepam and flumazenil, 10 mg/kg or 20 mg/kg, partial but not complete reversal of the potentiating effect of diazepam was observed, minimum air concentration values being 0.6% after diazepam alone and 0.8% after diazepam and flumazenil. However, mice pretreated intraperitoneally with flumazenil, in the concentration range 1-10 mg/kg, delivered as a solution in polyethylene glycol-Intralipid vehicle or as a suspension in saline, recovered control levels of spontaneous motor activity much faster than in the absence of flumazenil, on emergence from halothane-induced anaesthesia. In this range, the effect was not dose-dependent. These findings suggest that some of the effects of halothane are mediated at the level of the benzodiazepine receptor.

Anesthesia↗
PubMed1989

A model to decrease hepatic blood flow and cardiac output with pressure breathing.

This randomized, controlled, crossover study evaluated the effect of continuous positive airway pressure (CPAP) breathing on hepatic blood flow (HBF) and cardiac output in 10 healthy male subjects. A CPAP mask was placed on the face and the subject breathed at either CPAP 12.5 cm H2O or ambient airway pressure. The estimated HBF was calculated as the ratio of indocyanine green plasma clearance to one minus the hematocrit. Cardiac output was measured with Doppler ultrasound. CPAP caused HBF to decrease in 8 of 10 subjects (14.1% +/- 15.3%, mean +/- SD, p = 0.033) and cardiac index (CI) to decrease in all subjects (14.1% +/- 5.7%, p = 0.0001). Stroke volume and respiratory rate were significantly decreased; heart rate was unchanged. These results indicate that CPAP at 12.5 cm H2O causes a small, but significant decrease in both HBF and CI.

Adult↗
PubMed1989

Intraoperative complications in patients receiving amiodarone: characteristics and risk factors.

This article reviews amiodarone's adverse cardiovascular properties, concentrating on those in surgical patients, and evaluates several potential risk factors. Amiodarone has negative inotropic and chronotropic properties as well as peripheral vasodilating properties that may manifest as bradycardia, reduced cardiac output, and hypotension. These reactions are clinically important during surgery, because of resistance to pharmacologic resuscitation and an increased mortality rate. Potential risk factors include ventricular dysfunction, rapid infusion rate, hypocalcemia, cardiopulmonary bypass, general anesthesia, concurrent negative inotropic or chronotropic drugs, and an elevated serum amiodarone or desethylamiodarone concentration. The following measures may decrease the risk of intraoperative adverse reactions in amiodarone-treated patients. The serum calcium concentration should be at the physiologic level and the serum amiodarone and digoxin concentrations should be in the therapeutic range. Negative inotropic and chronotropic agents should be discontinued when possible. A temporary cardiac pacemaker may prevent intraoperative hypotension due to bradycardia. Amiodarone may be discontinued before surgery to minimize the risk of intraoperative complications, but this decision should balance the potential for amiodarone-associated intraoperative complications against the risk of arrhythmia recurrence and the delay of surgery.

Amiodarone↗
PubMed1989

Acute poisoning treated in the intensive care unit: a case series.

A retrospective study on patients with acute poisoning admitted to the Intensive Care Unit (ICU) of the Ichilov Hospital over a 3-year period (1982-84) is presented. Of 419 patients seen in the Emergency Room for intoxication during these years, 71 (17%) required intensive care upon admission. Suicide attempts accounted for 90% of the ICU admissions, with drugs of the benzodiazepine (BDZ) group being the most commonly used (51%). Mixed-drug overdose was seen in 55% of the patients. There was a poor correlation between the drugs suspected on admission and those actually detected in the blood. Although the total number of admissions due to poisoning increased in 1984 (21 in 1982 vs. 37 in 1984), mechanical ventilation was required by fewer patients (92% in 1982 vs. 51% in 1984) and for a shorter period of time (3.1 days in 1982 vs. 2.1 days in 1984), which resulted in a shorter ICU stay (4.8 days in 1982 vs. 3.1 days in 1984). The introduction of the new BDZ antagonist flumazenil may have partially accounted for this positive trend.

Acute Disease↗
PubMed1988

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.

Adult↗
PubMed1988

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.

Adolescent↗
PubMed1986

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.

Adult↗
PubMed1986

Rupture of the stomach in a diving accident with attempted resuscitation. A case report.

A compressed air diver suffered pulmonary barotrauma with arterial air embolization; resuscitation was unsuccessful. Attempts at resuscitation included mouth-to-mouth ventilation and cardiac massage. A chest radiograph taken during resuscitation revealed free intraperitoneal air. Postmortem examination showed rupture of the stomach. The two possible aetiological factors--barotrauma of ascent and cardiopulmonary resuscitation--are discussed.

Adult↗
PubMed1985

Effect of methyl prednisolone on normobaric pulmonary oxygen toxicity in rats.

Male albino rats were exposed to 81, 86, 90 or 99% oxygen until death. Rats were also administered methyl prednisolone (MP) 10-60 mg/kg/day intraperitoneally. MP-treated rats survived significantly less than controls: 53.5 +/- 4.7 vs. 65.2 +/- 8.2 h, p less than 0.001 in 99% O2, 74.4 +/- 9.4 vs. 120 +/- 39.8 h, p less than 0.02 in 86% O2 and 113.7 +/- 21.4 vs. 162 +/- 17.9 h, p less than 0.03 in 81% O2. Rats were exposed to 99% O2 for 10, 30 and 50 h and the activity of superoxide dismutase (SOD) and catalase in their lungs was monitored. MP-treated rats showed less increase in pulmonary SOD after 10 h (111 vs. 171%, p less than 0.03) but no effect on SOD activity thereafter. MP had no effect on the response of catalase to O2. No effect of MP on lung morphology could be found under the light microscope.

Animals↗