Ron Flaishon

A Risk-Benefit Assessment of Flumazenil in the Management of Benzodiazepine Overdose

SummaryThe worldwide expansion in the use of benzodiazepines has led to their frequent, and often inappropriate, use and to an increase in their involvement in self-induced poisoning and iatrogenic overdosing. Flumazenil is a specific and competitive antagonist at the central benzodiazepine receptor, reversing all effects of benzodiazepine agonists without tranquillising or anticonvulsant actions. Incremental intravenous bolus injections of flumazenil 0.1 to 0.3mg are the most effective and well tolerated in the diagnosis and treatment of pure benzodiazepine overdose; additional boluses or an infusion (0.3 to 0.5 mg/h) can be given to prevent patients from relapsing into coma. Intravenous flumazenil 10 to 20 µg/kg is effective in neonates and small children. Intramuscular, oral (20 to 25mg 3 times daily or as required) and rectal administration may be used as alternatives in long term regimens. Patients with mixed-drug overdose require higher doses (up to 2mg bolus, ≈1 mg/h infusion) to regain consciousness. Children and the elderly, chronically ill patients, and pregnant women and their fetuses all respond satisfactorily to flumazenil, but the usefulness of the drug in patients with hepatic encephalopathy and alcohol overdose is debatable.The use of flumazenil results in complete awakening with restoration of upper airway protective reflexes, thus enabling gastric lavage to be performed and transfer of the patient from the emergency room to another hospital department. Resumption of effective spontaneous respiration allows for expeditious extubation, weaning off mechanical ventilation or the avoidance of endotracheal intubation. While flumazenil is not associated with haemodynamic adverse effects, caution should be exercised when using this agent in patients who have co-ingested chloral hydrate or carbamazepine or whose ECG shows abnormalities typical of those seen after overdose with tricyclic antidepressants (TCAs); the use of flumazenil in the presence of these drugs can sometimes induce treatable cardiac dysrrhythmia.Flumazenil per se does not induce adverse effects. Coma reversal by flumazenil may cause mild, short-lived reactions caused by sudden awakening. Withdrawal symptoms in long term benzodiazepine users and seizures in patients who have taken an overdose of TCA or carbamazepine and a benzodiazepine can occur with flumazenil; these symptoms are avoidable by utilising slow flumazenil dose titration.

Antichemical protective gear prolongs time to successful airway management: A randomized, crossover study in humans

BackgroundAirway management is the first step in resuscitation. The extraordinary conditions in mass casualty situations impose special difficulties in airway management, even for experienced caregivers. The authors evaluated whether wearing surgical attire or antichemical protective gear made any difference in anesthetists’ success of airway control with either an endotracheal tube or a laryngeal mask airway. MethodsFifteen anesthetists with 2–5 yr of residency and wearing either full antichemical protective gear or surgical attire intubated or inserted laryngeal masks in 60 anesthetized patients. The study was performed in a prospective, randomized, crossover manner. The duration of intubation/insertion was measured from the time the device was grasped to the time a normal capnography recording was obtained. ResultsEndotracheal tubes were introduced significantly (P < 0.01) faster when the anesthetist wore surgical attire (31 ± 7 vs. 54 ± 24 s for protective gear), but the mean times necessary to successfully insert laryngeal masks were similar (44 ± 20 s for surgical attire vs. 39 ± 11 s for protective gear). Neither performance failure nor incidences of hypoxemia were recorded. ConclusionsThis first report in humans shows to what extent anesthetists’ wearing of antichemical protective gear slows the time to intubate but not to insert a laryngeal mask airway compared with wearing surgical attire. Laryngeal mask airway insertion is faster than tracheal intubation when wearing protective gear, indicating its advantage for airway management when anesthetists wear antichemical protective gear. If chances for rapid and successful tracheal intubation under such chaotic conditions are poor, laryngeal mask airway insertion is a viable choice for airway management until a proper secured airway is obtainable.

Direct Induction of Acute Lung and Myocardial Dysfunction by Liver Ischemia and Reperfusion

OBJECTIVES To investigate whether liver ischemia and reperfusion (IR) directly affect functions of remote organs. BACKGROUND Cardiovascular and respiratory dysfunction follows hemorrhage, spinal shock, or trauma as a result of no-flow-reflow phenomena. Hepatic IR induces remote organ damage probably by xanthine oxidase and oxygen species. MATERIALS AND METHODS Isolated rat livers, lungs, and hearts were perfused with Krebs-Henseleit solutions. After stabilization, livers were either perfused or made ischemic. Then, livers and hearts or livers and lungs were reperfused in series, and the liver was disconnected and the second organ continued to perfuse with the accumulated effluents. MEASUREMENTS AND MAIN RESULTS Ischemic and reperfused liver effluent contained high lactate dehydrogenase and uric acid concentrations compared with controls; xanthine oxidase increased 60 to 100 times. Ischemic and reperfused lung peak inspiratory pressure almost doubled; airway static compliance halved; myocardial contractility decreased to 70% of baseline; wet weight-to-dry weight ratios of lungs and livers increased. CONCLUSION Ischemic and reperfused liver can directly induce myocardial and pulmonary dysfunction, presumably by oxidant-induced injury.

Laryngeal Mask Airway Insertion by Anesthetists and Nonanesthetists Wearing Unconventional Protective Gear A Prospective, Randomized, Crossover Study in Humans

BackgroundMass casualty situations impose special difficulties in airway management, even for experienced caregivers. The laryngeal mask airway is part of the difficult airway algorithm. The authors evaluated the success rate and the time to secure airways by mask by anesthetists, surgeons, and novices when wearing either surgical attire or full antichemical protective gear that included butyl rubber gloves and a filtering antigas mask. MethodsTwenty anesthetists and 22 surgeons with 2–5 yr of residency inserted a laryngeal mask airway in 84 anesthetized patients, and 6 novices repetitively inserted masks in 57 patients under both conditions in a prospective, randomized, crossover manner. The duration of insertion was measured from the time the device was first grasped until a normal capnography recording was obtained. ResultsAnesthetists needed 39 ± 14 s to insert the masks when wearing surgical attire and 40 ± 12 s with protective gear. In contrast, surgery residents needed 64 ± 40 and 102 ± 40 s (P = 0.0001), respectively. Anesthetists inserted masks in a single attempt, whereas the surgeons needed up to four attempts with no hypoxia or failure associated. The initial attire-wearing novices’ insertions took as long as the surgeons’; three of them then reached the mean performance time of the anesthetists after four (protective gear) and two (surgical attire) trials, with only one occurrence of hypoxia and a failure rate similar to that of the surgeons. ConclusionsAnesthesia residents insert laryngeal mask airways at a similar speed when wearing surgical attire or limiting antichemical protective gear and two to three times faster than surgical residents or novices wearing either outfit. Novices initially perform at the level of surgical residents, but their learning curve was quick under both conditions.

An evaluation of general and spinal anesthesia techniques for prostate brachytherapy in a day surgery setting

We evaluated four anesthetic techniques for transperineal brachytherapy of the prostate in a day-surgery setting: general anesthesia with either fentanyl and propofol total IV anesthesia (TIVA) or with fentanyl, thiopental, and isoflurane (F-P-I), versus spinal block using 5 mg of 0.5% large-dose spinal hyperbaric bupivacaine (LDS) or 2.5 mg of 0.5% hyperbaric bupivacaine plus fentanyl 25 &mgr;g small-dose spinal (SDS). Operating room time was shorter in the general anesthesia groups. TIVA patients voided earlier (103 ± 41 min) than F-P-I patients (131 ± 65 min), SDS (126 ± 55 min), and LDS patients (169 ± 65 min; P < 0.05 TIVA versus all groups and between spinal groups). TIVA patients were discharged earlier (119 ± 42 min) than F-P-I patients (160 ± 69 min) and SDS or LDS patients (132 ± 53 and 186 ± 72 min, respectively; P < 0.05 versus all groups and between the spinal groups). There were no intergroup differences regarding postanesthesia nausea or vomiting, pain score, return to normal function at home, or overall satisfaction. Whereas all four techniques are suitable for this procedure, TIVA provides the earliest voiding and consequently fastest discharge. Between spinal techniques, the SDS technique requires more intraoperative sedation but provides earlier voiding and consequently earlier discharge. TIVA, general anesthesia with isoflurane and fentanyl, and two spinal techniques (5 mg of bupivacaine 0.5% or 2.5 mg of bupivacaine 0.5% plus 25 &mgr;g of fentanyl) are suitable techniques for transperineal brachytherapy in the day-surgery setting. TIVA allows for earliest voiding and therefore fastest discharge home. Spinal block with 2.5 mg of bupivacaine plus 25 &mgr;g of fentanyl provides earlier voiding and consequently earlier discharge than 5 mg of bupivacaine alone.

Cross-sensitivity between isoflurane and diazepam : Evidence from a bidirectional tolerance study in mice

We examined in mice the effect of chronic diazepam treatment on the sensitivity to isoflurane, and that of repeated isoflurane exposure on the sensitivity to diazepam. Mice were divided into four groups: group 1, treated with diazepam, 10 mg/kg i.p. twice daily; group 2, vehicle-treated controls; group 3, exposed to 3% isoflurane for 25 min twice daily; and group 4, untreated controls. After 14 days the effect of the treatment was assessed. Twenty-four hours after the last 10 mg/kg diazepam treatment, groups 1 and 2 received diazepam, 5 mg/kg i.p., and were subjected to the horizontal wire test (HWT). All control mice but only 10% of the diazepam-treated mice failed the HWT. Groups 1 and 2 were then exposed to increasing concentrations of isoflurane. Diazepam-treated mice (group 1) lost the HWT at 0.7+/-0.7%, compared with 0.6+/-0.1% in controls (group 2) (P<0.001); the ED50 was 0.75% vs. 0.65%. Group 1 mice lost the righting reflex at 0.94+/-0.07% isoflurane vs. 0.87+/-0.06% in group 2 (P<0.01); the ED50 was 0.93% vs. 0.82%. Recovery time was 175+/-161 s in group 1 vs. 343+/-275 s in group 2 (P<0.02). Twenty-four hours after the last of the repeated exposures to isoflurane, we examined the responses of groups 3 and 4 to increasing concentrations of isoflurane. Mice in group 3 lost the righting reflex at 1.0+/-0.06% isoflurane vs. 0.9+/-0.04% in controls (group 4) (P<0.001); the ED50 was 0.96% vs. 0.85%. Recovery time was 113+/-124 s vs. 208+/-126 s in groups 3 and 4 (P<0.09). Diazepam, 3 mg/kg i.p. administered to groups 3 and 4, caused loss of the HWT reflex in 33% of group 3 mice and in 82% of controls (group 4) (P<0.001). It appears that prolonged exposure to both diazepam and isoflurane caused reduced sensitivity to each drug separately, as well as to the other drug. This finding may strengthen the theory that inhalational anesthetics may act via the same mechanism as the benzodiazepines.

Blood Flow Versus Hematocrit in Optimization of Oxygen Transfer to Tissue During Fluid Resuscitation.

The effectiveness of fluid resuscitation regimens in hemorrhagic trauma is assessed based on its ability to increase oxygen concentration in tissue. Fluid resuscitation using both crystalloids and colloids fluids, creates a dilemma due to its opposing effects on oxygen transfer. It increases blood flow thereby augmenting oxygen transport but it also dilutes the blood simultaneously and reduces oxygen concentration thereby reducing oxygen transport. In this work we have studied these two opposing effects of fluid therapy on oxygen delivery to tissue. A mathematical model of oxygen diffusion from capillaries to tissue and its distribution in tissue was developed and integrated into a previously developed hemodynamic model. The capillary-tissue model was based on the Krogh structure. Compared to other models, fewer simplifying assumptions were made leading to different boundary conditions and less constraints, especially regarding capillary oxygen content at its venous end. Results showed that oxygen content in blood is the dominant factor in oxygen transport to tissue and its effect is greater than the effect of flow. The integration of the capillary/tissue model with the hemodynamic model that links administered fluids with flow and blood dilution indicated that fluid resuscitation may reduce oxygen transport to tissue.