Ron Ben Abraham

Role of the molecular adsorbent recycling system (MARS) in the treatment of patients with acute exacerbation of chronic liver failure.

ObjectiveTo test the efficacy of the molecular adsorbent recycling system (MARS) in patients with acute exacerbation of chronic liver disease. DesignA prospective case analysis. SettingA university-affiliated tertiary medical center. Patients and Methods We applied MARS to treat a consecutive series of eight patients with acute exacerbation of chronic liver disease. ResultsThe overall survival rate was 62.5%. All patients demonstrated improvement with regard to their degree of encephalopathy. In three patients, intracranial pressure and jugular bulb oxygen saturation decreased and cerebral perfusion pressure increased after treatment institution. Patients’ hyperdynamic state was attenuated, as demonstrated by elevation of systemic vascular resistance, mean arterial pressure, and parallel reduction in cardiac index. A prompt reduction in serum ammonia, bilirubin, and lactate levels was observed. There were no complications during the treatment period. ConclusionsApplying MARS treatments to patients with acute exacerbation of chronic liver disease can detoxify blood, improve cerebral circulation, and reduce brain edema, as reflected by the reduction in intracranial pressure and jugular bulb oxygen saturation values in our patients. A partial reversal of the characteristic hyperdynamic circulation was also achieved. Despite our encouraging results, further testing is needed to determine the reliability of the system.

Practical Guidelines for Acute Care of Victims of Bioterrorism: Conventional Injuries and Concomitant Nerve Agent Intoxication

THE potential use of weapons of mass destruction has recently become a real threat even in regions of the world that are remote from areas of ongoing armed conflicts. Episodes of the use of sarin or VX, both potent acetylcholinesterase (AChE) inhibitors that cause cholinergic crisis, in the terrorist attacks against civilians in Japan in 1994 and 1995 which produced several fatalities and hundreds of casualties, 1,2 and the military use of nerve agents (NA) by Iraq against Iran and the Kurdish population during the 1980s are grim examples of the deadly potential of NA. Victims of a mass casualty event can suffer from physical trauma alone or from trauma in combination with gas intoxication. The exposure of a physically injured patient to a toxic substance, in a scenario of mass injury, has recently gained major attention among planners of future protocols for emergency medical services. 3 Furthermore, when a civilian population becomes the prime target of an NA attack, diversity in age and previous health status are expected to increase the extent of the injuries compared with those of healthy adult soldiers by as much as 10-fold. 4 Because rapid deterioration and multiorgan involvement are to be expected after a physically injured individual is exposed to a toxic substance, proper organization and complex but efficient acute medical and surgical care systems must be organized and deployed to ensure a maximal number of saved lives. The various national rescue forces that have traditionally been tasked with models of rapid evacuation and decontamination of large numbers of poisoned civilians from affected areas appear to be only a fraction of future necessities. 5 The proposed management of mass casualty events needs to be based on triage principles and acute care measures. These should include: rapid identification of the offending agent, swift decontamination by wellprotected emergency medical personnel, and triageguided mass evacuation to a nearby medical facility that should be well equipped and staffed with personnel who have been properly trained to deal with such multifaceted events.

Dextromethorphan mitigates phantom pain in cancer amputees.

AbstractBackground: Hyperexcitability of N-methyl-d-aspartate (NMDA) receptors may play a role in the persistence of phantom pain. Dextromethorphan (DM) blocks NMDA receptors. Methods: Eight cancer and two noncancer amputees with established, disabling phantom pain received oral DM 60 or 90 mg twice daily (BID) in a three-period double-blind crossover placebo-controlled trial. This followed an open-phase trial in which either dose was given three times daily if pain relief during the double-blind phase was <50% of pretreatment intensity. Patients then underwent a 3-month phase of treatment with the best regimen and a subsequent 1-month posttreatment follow-up. Results: All patients reported a >50% decrease in pain intensity, better mood, and lower sedation in each treatment phase. Four individuals reported this level of pain relief with the 60-mg and one with the 90-mg BID regimen during the double-blind phase, whereas two amputees benefited from the 60-mg and three from the 90-mg thrice-daily regimen in the open-phase trial. One reported exacerbation of pain with the 90-mg BID regimen, and three reported pain rebound at the 1-month posttreatment follow-up phase. Three patients stopped all previous analgesic use during the study. Conclusions: Persistent phantom pain probably involves NMDA receptor hyperexcitability because DM 120 to 270 mg/day mitigated the pain satisfactorily.

Lung preconditioning with N-acetyl-L-cysteine prevents reperfusion injury after liver no flow-reflow: a dose-response study.

Background. Circulating xanthine oxidase activity and the generated oxidants have been linked to lung reperfusion injury from no flow-reflow conditions in other organs after organ transplantation or surgery. N-acetyl-l-cysteine (NAC), an oxidant scavenger, promotes glutathione in its reduced form (GSH) that is depleted during ischemia. We have recently demonstrated its efficacy in protecting lungs from reperfusion injury if administered during reperfusion of postischemic liver. We now investigated whether preconditioning of lungs with NAC could attenuate lung respiratory or vascular derangement after no flow-reflow (ischemia-reperfusion, IR) and if this depends on lung GSH levels. Methods. Rat isolated livers were stabilized and perfused with modified Krebs-Henseleit solution (KH) (control, n=12) or made ischemic (no flow, IR-0, n=12) for 2 hr. Meanwhile, lungs were isolated, ventilated, and stabilized (KH+bovine albumin 5%). Serial perfusion (15 min) of liver+lung pairs took place followed by lung only recirculation (45 min) with the accumulated solution. Another three controls and three ischemic groups included lungs treated during stabilization with NAC at 100 mg·kg−1, 150 or 225 mg·kg−1 (in 2.5, 3.7 or 5.5 mmol solutions, respectively). Results. Ischemic liver damage, expressed by circulating hepatocellular constituents, was associated with pulmonary artery and ventilatory pressure increases by 70–100% of baseline, abnormal wet-to-dry weight ratio, and abnormal bronchoalveolar lavage volume and content in the IR-0 (nontreated) and the IR-100 and IR-225 pretreated lungs. NAC-150 pretreatment afforded preservation for most parameters. GSH content in the IR-150 lung tissue was only 11% higher than that of IR-225, but 2-fold that in IR-0 and IR-100 GSH lungs. Conclusion. Lung preconditioning with NAC prevents reperfusion injury but not in a dose-related manner. Although enhanced GSH tissue content explains lung protection, GSH-independent NAC activity is another possibility.

Dextromethorphan for phantom pain attenuation in cancer amputees: a double-blind crossover trial involving three patients.

BackgroundPhantom limb pain is an intriguing pain syndrome that may result from damage to peripheral nerve tissue but could also involve central amplifying congeners. N-methyl-d-aspartate (NMDA)-receptor antagonists were recently shown to alleviate neuropathic pain in both animal and human models. Dextromethorphan is a noncompetitive NMDA-receptor antagonist. Study DesignOral dextromethorphan (120–180 mg daily) was administered to three selected cancer patients during a 3-week study and an additional 1 month of treatment with the dosage subjectively judged to be best. ResultsOral dextromethorphan effectively reduced postamputation phantom limb pain, bestowing improvement in feeling and minimizing sedation in comparison with the pretreatment or placebo conditions, with no side effects. Pain recurred in one patient 1 month after treatment was stopped. ConclusionsFurther clinical trials are warranted to determine the optimal dosage and identify which patients with phantom pain would benefit the most from this therapeutic approach.

Wrist Actigraphy in Anesthesia

STUDY OBJECTIVES To examine the use of wrist actigraphy during and following anesthesia or monitored sedation and its ability to objectively assess sleep-related events. DESIGN Uncontrolled study. SETTING 1100-bed tertiary care municipal, university-affiliated medical center. PATIENTS AND INTERVENTIONS 18 patients who underwent minor to medium lower-body surgical procedures with spinal or epidural anesthesia with sedation by propofol, midazolam, or isoflurane-based general anesthesia. MEASUREMENTS AND MAIN RESULTS Wrist actigraphy was measured and evaluated. The actigraphic recordings accurately indicated the presence and time of occurrence of all relevant perioperative events including those related to anesthesia. Actigraphic data were more precise than equivalent attending anesthesiologists subjective observations. The anesthesiologist detected changes in the patients activity with a delay of minutes after they had been picked up by the actigraph. The integrated areas of recorded phases of midazolam-induced sedation and the occurrence and reversal of paradoxical reactions were distinctly discernible as such, unlike the less specifically defined description of the anesthesiologist. CONCLUSIONS Real time actigraphic monitoring can provide clear-cut and objective indications of changes in the depth of anesthesia or sedation and its associated events during surgery and recovery.

Gray–white matter discrimination—a possible marker for brain damage in heat stroke?

INTRODUCTION/OBJECTIVE Heat stroke (HS) is a common medical emergency which carries high morbidity and morality. This study was designed to describe the pattern of central nervous system (CNS) changes as detected by brain CT scan in a case series of six patients suffering from classical and exertional HS. METHODS AND PATIENTS All the patients were admitted in critical condition during the heat wave in the summer of 1999 in Israel. Each was in deep coma with a measured core temperature of over 40 degrees C upon admission to the emergency department. RESULTS Aggressive cooling measures decreased the core temperature to <38 degrees C within 30 min following admission. Two patients (33.3%) died. One of the survivors remained in a vegetative state. Brain CT studies carried out within 4 days of admission in all the patients revealed severe loss of gray-white matter discrimination (GWMD) without signs of acute bleed or significant focal lesion, findings that persisted in repeated brain CTs in one patient who remained in a vegetative state. DISCUSSION AND CONCLUSIONS Loss of GWMD may represent an early and sensitive indication of severe brain damage in patients with severe HS. Further studies in larger groups of patients are warranted in order to determine whether the appearance of GWMD in brain CTs of patients with HS has prognostic value.

Electromechanical impairment of human auricle and rat myocardial strip subjected to exogenous oxidative stress

OBJECTIVE Animal myocardial dysfunction induced by remote ischemia-reperfusion (IR) was shown to be partly accomplished via a direct effect of the pro-oxidant xanthine oxidase (XO). This direct remote effect was not tested in humans. We now assessed the performance of human auricles in the presence of solutions containing XO and/or allopurinol and compared them to those of rat myocardial strips. METHODS Human and rat specimens (n=64) were separately exposed for 2h to Krebs-Henseleit solution that either (1) exited from rat livers that were earlier perfused for 2h (control-human or control-rat), (2) exited from livers that were earlier made ischemic for 2h (IR-human, IR-rat), (3) contained xanthine (X) 3.8 microM + XO 3 mU ml(-1) (X+XO-human, X+XO-rat), or (4) exited from post 2h-ischemic livers and contained 100 microM allopurinol (human or rat IR + allopurinol groups). RESULTS Unlike the unchanged electromechanical performance in the control and IR+allopurinol auricles and strips, the rates of contraction, maximal force of contraction and working index of either preparation were reduced by 75-98% (P<0.01) when exposed to the IR reperfusate or to the X+XO-enriched Krebs. The basal amplitudes of contraction in these four latter groups increased twofold (P<0.01). XO activity was similarly low in the control and in the IR+allopurinol groups, but four- to 45-fold (P<0.001) higher in the IR and the X+XO groups, both in the rat and human organs. The reduced glutathione was reduced by approximately 50% (P<0.01) in either preparation in the IR and the X+XO groups compared to the control and IR+allopurinol groups. CONCLUSIONS Remotely and exogenously originated oxidative burst directly induces electromechanical dysfunction and disrupts oxidant/antioxidant balance in human auricles as it does in the rat myocardial strip.

Metabolic and clinical markers of prognosis in the era of CT imaging in children with acute epidural hematomas

Acute epidural hematoma (AEH), a relatively common complication of head injury in children, persists in bearing high morbidity and mortality. Early establishment of prognosis could guide optimal patient allocation, and early identification of predictive signs could assist in choosing appropriate therapeutic interventions. This study aimed to delineate expeditiously obtainable prognostic markers for determining outcome in a subset of children with AEH. We reviewed our 11-year experience with 61 consecutive children <16 years old with head trauma and isolated AEH. Treatment followed a standard advanced trauma life support protocol. A medical history was obtained, and all patients underwent neurosurgical and physical evaluations. CT scans were performed, as were laboratory tests which included arterial blood gases, glucose, electrolytes (K+, Na+), hemoglobin and coagulation studies. Evaluation of the data collected on cause of injury, interval between trauma occurrence and presentation, clinical symptoms, Glasgow Coma Scale (GCS) scores, vital signs, laboratory test results, physical findings and surgical versus conservative management revealed that the best single predictors of outcome following AEH were the GCS and focal neurological deficits. Of all laboratory data obtained on admission, the blood potassium, pH and glucose test results correlated significantly with prognosis. Prognosis can be adequately and expeditiously estimated by selected markers within a comprehensive evaluation of children with AEH.

Mannitol Dose-Dependently Attenuates Lung Reperfusion Injury Following Liver Ischemia Reperfusion: A Dose-Response Study in an Isolated Perfused Double-Organ Model

We had previously studied different modes of prevention of liver ischemia-reperfusion (IR)-induced remote organ reperfusion injury, a challenge that remains partly unmet. We have now studied the capability of mannitol at different doses in abrogating liver IR-induced lung reperfusion injury in an isolated double-organ model. Rat livers (n = 8/group) were perfused with Krebs-Henseleit solution (control) or made globally ischemic (IR) for 2 h, after which they were paired with normal lungs and “reperfused” together for 15 min. The lungs were then perfused alone with the accumulated Krebs for an additional 45 min. Another 4 control and 4 IR pairs were reperfused with Krebs containing mannitol at .22 mmol, .55 mmol, .77 mmol, or 1.1 mmol. Mannitol .22 mmol and 1.1 mmol failed to attenuate IR-lung injury as indicated by 50–95% increases in inspiratory and perfusion pressures and compliance reduction, a 70% increase in weight gain, and a 2–50-fold increase in bronchoalveolar lavage volume and content. Mannitol .55 mmol prevented all these abnormalities, and .77 mmol attenuated only changes in ventilatory parameters. The latter two treatments were also associated with a 50% reduction in xanthine oxidase activity and a 35–45% increase in the reduced glutathione tissue content compared with the nontreated IR-paired lungs. It is concluded that mannitol in a narrow therapeutic dose range can reduce oxidalive stress-induced lung damage that is related to liver IR.