Oded Szold

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.

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.

Permissive hypercapnia ventilation in patients with severe pulmonary blast injury.

OBJECTIVES To describe our experience with the use of limited peak inspiratory pressure (PIP), volume-controlled ventilation, and permissive hypercapnia in patients with severe pulmonary blast injury. METHODS Patients with pulmonary blast injury were ventilated using volume-controlled, synchronized intermittent mandatory ventilation. Whenever PIP exceeded 40 cm H2O, the tidal volume was decreased to maintain PIP at less than 40 cm H2O. Whenever the arterial pH fell below 7.2, the ventilator rate was increased in increments of 2 breaths per minute until the arterial pH rose to 7.25. RESULTS Between 1994 and 1996, 17 patients with severe pulmonary blast injury (10 from enclosed space explosions and seven from open space ones), requiring mechanical ventilatory support were admitted to our intensive care unit. Four patients developed increasing PaCO2 levels (to 93 +/- 12 mm Hg) associated with the reduction in arterial pH that was corrected by increasing the ventilator rate. There was evidence of ventilator-induced pulmonary barotrauma. Of the 17 patients, 15 patients (88%) survived. CONCLUSIONS Limited PIP in a volume-controlled ventilation is a useful and safe mode of mechanical ventilation in patients with pulmonary blast injury.

Methylene Blue Prevents Pulmonary Injury after Intestinal Ischemia-reperfusion

OBJECTIVE To investigate the effect of methylene blue, an inhibitor of oxygen radicals, on lung injury caused by reperfusion of ischemic tissue. METHODS Intestinal ischemia-reperfusion injury was induced in rats by clamping the superior mesenteric artery for 1 hour. Thereafter, the experimental group was administered 1% methylene blue intraperitoneally and the control group received saline. After 4 hours, pulmonary histopathologic features were assessed, and lung wet-weight to dry-weight ratios and tissue xanthine oxidase were determined. RESULTS The control group suffered from severe pulmonary parenchymal damage, compared with slight damage in the experimental group. The number of sequestered neutrophils was significantly higher in the control group (319 +/- 60 polymorphonuclear cells per 10 high-power fields) than in the methylene blue-treated group (91 +/- 8 polymorphonuclear cells per 10 high-power fields; p < 0.001). The wet-weight to dry-weight ratio was significantly increased in the saline-treated rats compared with the methylene blue-treated group (6.19 +/- 0.28 vs. 5.07 +/- 0.21; p < 0.001). Xanthine oxidase activity was similar in both groups. CONCLUSION Methylene blue attenuated lung injury after intestinal ischemia-reperfusion. Inhibition of oxygen free radicals may be the protective mechanism.

Inhaled nitric oxide improves pulmonary functions following massive pulmonary embolism: a report of four patients and review of the literature.

Acute pulmonary embolism increases pulmonary vascular resistance and may lead to acute right ventricular failure and cardiocirculatory collapse and respiratory failure, possibly resulting in substantial morbidity and mortality. Inhaled nitric oxide (NO) dilates pulmonary blood vessels and has been used to reduce pulmonary vascular resistance in patients with chronic thromboembolic pulmonary hypertension and acute respiratory distress syndrome. This case series describes our experience with inhaled NO administered to four patients suffering from acute massive pulmonary embolism following abdominal surgery. The four described patients recovering from small bowel resection, pancreatoduodenectomy, hemipelvectomy, or recent gastrointestinal bleeding had severe respiratory and hemodynamic deterioration due to pulmonary embolism. Each received inhaled NO (20–25 ppm) via the inspiratory side of the breathing circuit of the ventilator. Pulmonary and systemic blood pressures, heart rate, and lung gas exchange improved in all the patients within minutes after the initiation of NO administration. Inhaled NO may be useful in treating acute massive pulmonary embolism. This potential application warrants further investigation.

Kerosene-induced severe acute respiratory failure in near drowning: reports on four cases and review of the literature.

OBJECTIVE The purpose of this study is to present an unusual respiratory and cardiovascular course after intoxication and near drowning in a river contaminated with kerosene. DESIGN Case reports and review of the literature. SETTING Intensive care unit of a university-affiliated hospital. PATIENTS Four patients after near drowning. INTERVENTION Supportive only. RESULTS The four patients developed acute respiratory failure. Cardiomyopathy was present in three patients and a persistent hypokalemia in two patients. The onset of the symptoms was delayed, which led to underestimation of the severity of their illness. Two of the four patients died. The diagnosis of hydrocarbon intoxication was based on bronchoalveolar lavage results, neutrophilic alveolitis with the presence of lipid-laden macrophages, and evidence of lipoid pneumonia from the autopsy performed on one victim. One patient who clinically deteriorated and another who developed a severe restrictive pulmonary disorder were treated with corticosteroids, which were effective only in the latter patient. CONCLUSIONS Acute kerosene intoxication in a near-drowning event often results in severe respiratory and cardiac failure, with a high fatality rate. Treatment with corticosteroids may lead to a rapid improvement in lung function.

Usage of Blood Products in Multiple-Casualty Incidents The Experience of a Level I Trauma Center in Israel

OBJECTIVE To predict how much blood will be needed based on the number of injured patients arriving after a multiple-casualty incident. DESIGN A retrospective study evaluating data collected in 18 consecutive terrorist attacks in the city of Tel Aviv between January 1997 and February 2005. SETTING A large, urban trauma center. PATIENTS A total of 986 patients in 18 events. MAIN OUTCOME MEASURES Number of packed red blood cell (PRBC) units transfused per patient. RESULTS A total of 332 U of PRBCs were transfused. Half of the PRBC units were administered as massive transfusions to 4.7% of the patients. The number of PRBC units transfused per patient index (PPI) was related to incident size (mean [SD], 0.70 [1.60] to 1.50 [1.60]). The most frequent major blood group transfused was type O (50%). Half of the units of PRBCs were supplied during the first 2 hours. CONCLUSIONS One unit of blood per evacuated victim is sufficient in a small multiple-casualty incident and 2 U is sufficient in a large multiple-casualty incident. Half of the PRBC units should be blood group O.

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.

Selective attenuation of acute lung ventilatory injury by methylene blue after liver ischemia-reperfusion: a drug response study in an isolated perfused double organ model.

Background. Liver transplantation-related ischemia-reperfusion (IR) is associated with the generation of stress oxidants that can spread damage remotely. Methylene blue (MB) had been shown to reduce lung neutrophils sequestration after in vivo intestinal IR and to have a dose-dependent potential for abrogating oxidant-induced ex vivo aortal ring reperfusion injury after liver IR. We now investigated MB’s dose-dependent capabilities in preventing acute lung injury after the same liver IR. Methods. Wistar rat livers (eight replicates/group) were perfused (control) with modified Krebs-Henseleit solution or put globally in no flow (IR) conditions for 2 hr. Separately prepared lungs were then paired with livers and “reperfused” (15 min) together. The livers were then removed, and the lungs were left to recirculate alone with the accumulated Krebs for 45 min. Three additional control and three IR groups were reperfused with Krebs containing 20, 40, or 60 mg/kg MB at concentrations of 42, 86, or 128 &mgr;M. Results. All IR livers had hepatocellular and biochemical abnormalities compared with normal functions in the controls. Liver IR was associated with a 50%–75% increase in lung ventilation and perfusion pressures, vascular resistance and decreased compliance, and abnormal bronchoalveolar lavage (BAL) volume and content. Adding 42 and 86 &mgr;M MB selectively maintained normal the vascular parameters, intra-experimental lung weight gain, BAL indices, and wet-to-dry ratios. MB128 &mgr;M but not 42 or 86 &mgr;M best prevented IR-induced deterioration in lung ventilatory pressure and compliance. Conclusions. MB selectively affords maintenance of normal lung ventilatory versus vascular measures after liver ischemia-reperfusion. Its proposed differential mechanism of action is discussed.

Acute lung injury following pancreas ischaemia‐reperfusion: role of xanthine oxidase

Background  Acute pancreatitis can lead to increased pulmonary vascular permeability and respiratory failure. Oxidants (and their generator, xanthine oxidase (XO)) play an important role in injuring the structural integrity of the pulmonary epithelium and endothelium, but their importance in the induction of acute lung injury following pancreas ischaemia‐reperfusion (IR) has not been defined.