Utilization profile of emergency department by irregular migrants and hospitalization rates: lessons from a large urban medical center in Tel Aviv, Israel.

BACKGROUND: Irregular migrants (IMM) are excluded from the National health insurance in most developed countries and may use the emergency department (ED) as a source for medical care. This study aims to compare the use of ED by IM with that of Israeli citizens (IC) in a large urban hospital in Tel Aviv, including socio-demographic characteristics, hospitalization proportion and medical conditions on admission. METHODS: This cross-sectional study included all IM and IC patients older than 18 years who attended the ED between 2007 and 2011, and compared their socio-demographic characteristics, the administrative details of the visit and clinical variables upon admission. Hospitalization proportion was calculated by dividing the number of patients who were admitted to the hospital ward by the number of all patients who attended the ED. RESULTS: IM who attended the ED were younger compared to IC (mean 39 ± 17 versus 52 ± 22 years, respectively), mostly males (1.4 Male/Female ratio) and mainly originated from developing countries. IM were more commonly self-referred, more likely to attend the ED during evening hours and weekends, complained of occupational injuries and frequented the surgical rather the medical ward of the ED compared with IC. IM stayed at the ED for longer periods than IC, yet the proportion of their hospitalization was lower than that of IC (19.4% versus 23.5%, respectively). CONCLUSION: IM stayed in the ED for longer periods and were less likely to be admitted to the hospital wards, suggesting presentation of non-severe medical conditions or possible barriers in ensuring care continuity in the community following discharge. Minimizing the barriers of IM to primary care in the community can reduce unnecessary referrals to the ED. Additionally, hospitals managements should respond to the high-volume of IM by shifting staff to busy hours and improving the communication with IM.

Perturbed threat monitoring following a traumatic event predicts risk for post-traumatic stress disorder.

BACKGROUND: Post-traumatic stress disorder (PTSD) is a chronic and difficult to treat psychiatric disorder. Objective, performance-based diagnostic markers that uniquely index risk for PTSD above and beyond subjective self-report markers could inform attempts to improve prevention and early intervention. We evaluated the predictive value of threat-related attention bias measured immediately after a potentially traumatic event, as a risk marker for PTSD at a 3-month follow-up. We measured the predictive contribution of attentional threat bias above and beyond that of the more established marker of risk for PTSD, self-reported psychological dissociation. METHOD: Dissociation symptoms and threat-related attention bias were measured in 577 motor vehicle accident (MVA) survivors (mean age = 35.02 years, 356 males) within 24 h of admission to an emergency department (ED) of a large urban hospital. PTSD symptoms were assessed at a 3-month follow-up using the Clinician-Administered PTSD Scale (CAPS). RESULTS: Self-reported dissociation symptoms significantly accounted for 16% of the variance in PTSD at follow-up, and attention bias toward threat significantly accounted for an additional 4% of the variance in PTSD. CONCLUSIONS: Threat-related attention bias can be reliably measured in the context of a hospital ED and significantly predicts risk for later PTSD. Possible mechanisms underlying the association between threat bias following a potentially traumatic event and risk for PTSD are discussed. The potential application of an attention bias modification treatment (ABMT) tailored to reduce risk for PTSD is suggested.

Non-collision injuries in public buses: a national survey of a neglected problem.

OBJECTIVES: This prospective, nationally representative, multi-centre study was undertaken to assess non-collision injuries sustained by public bus passengers in Israel. METHODS: The emergency departments (EDs) of six medical centres, which participated in this eight month study, were chosen to represent both urban and rural catchment areas. All patients diagnosed with injuries sustained on a public bus not involved in a road traffic accident were promptly evaluated for mechanism and nature of injury and demographic parameters. RESULTS: The study cohort consisted of 120 patients (86 were female, 34 were male, age range 3-89 years). Over half were older than 55 years. The most common injuries were to the limbs, vertebral column, and head. The major mechanism of injury was acceleration/deceleration. Most patients were standing when they sustained the injuries. There were no fatalities, and 17 patients were admitted to hospital (9 of 17, 52% older than 55 years). Extrapolation to yearly national statistics suggests a probable total of 729 such injuries. CONCLUSION: The significant injuries inflicted on passengers of public buses not involved in road traffic accidents warrant decisive preventative measures by transportation authorities.

Development of the specialty of emergency medicine in Israel: comparison with the UK and US models.

OBJECTIVES: To describe the development of emergency medicine (EM) in Israel and review the specific problems faced by the discipline and describe the solutions that were found. METHODS: A comprehensive literature search was conducted for data on development of EM in the UK and in North America, and the personal knowledge of two of the authors (PH and YW) was used in preparing the article. RESULTS: There are differences in development of EM between Israel and the UK/US models. In Israel the specialty developed within the context of established high quality clinical practice and consequently it met resistance from the system, which did not wish to invest in what it felt might be marginal improvements in patient care. The economics of Israeli medicine also dictated that EM be made into a super-specialty rather than a primary specialty. Certified specialists from family medicine, paediatrics, internal medicine, general surgery, anaesthesia, and orthopaedic surgery can access training positions in EM. Currently there are seven active EM programmes of 2.5 years duration and 16 residents. The curriculum is flexible and a national certification examination is being developed. CONCLUSIONS: Development of EM can and should take different paths according to the specific local needs and realities. There is no single ideal model suitable for all circumstances. The practice of clinical EM in Israel is comparable with that of any developed country and daily progress is being made in the academic areas of teaching and research. There are worldwide similarities in the process of developing EM as a distinct discipline.

Envenomation by Trachinus draco in the eastern Mediterranean.

Injuries caused by weever fish ( spp) are probably more ubiquitous than reported. Such injuries are extremely painful and require prompt treatment. Only relatively few clinical descriptions of envenomation have been published. We present three patients with envenomation and describe their treatment. Two patients were fishermen injured while handling caught fish and one was a tourist wading into the sea for pleasure. The clinical picture was dominated by extreme pain, which responded partly to the application of warm water, and usually necessitated systemic opiates for adequate control. Follow-up in one of the patients indicated prolonged, slow recovery of the local inflammatory reaction. Prompt analgesia is the mainstay of treatment of this non-lethal but extremely painful envenomation, with the application of hot water being effective, although not always completely.

Analysis of mechanical stresses within the alveolar septa leading to pulmonary edema.

Mechanical ventilation has been associated with pulmonary edema in the clinical setting, but the pathophysiological mechanisms of this process have not been clearly defined. Experimental studies have shown that high transpulmonary pressures resulting from ventilation may damage the capillary walls, thereby leading to edema. Knowledge of the stress distribution within the alveolar septa would be an important step in understanding this phenomenon. A newly developed saline-filled alveolar sac model was utilized for analysis of septal stresses in young and aging healthy lungs, in order to examine their vulnerability to pulmonary edema during ventilation. Significant stress concentrations were shown to develop near highly curved regions (small local radii of less than 4 mum in a lung inflated to 80% could be as high as 25 times that of average septal stresses. The combination of elevated stress sites that are formed in the stiffer parenchyma of the aging lung, together with the cyclic loading of ventilation, may explain the gaps and breaks previously observed in pulmonary edema.

An earthquake disaster in Turkey: assessment of the need for plastic surgery services in a crisis intervention field hospital.

On August 17, 1999, an earthquake of 7.4 magnitude struck Turkey, resulting in the destruction of the cities Golcuk, Izmit, Adapazari, and Yalova. Three days later, the Israel Defense Force Field Hospital arrived at Adapazari, serving as a reinforcement hospital until the rehabilitation of the local medical facilities. Surgical services in the field hospital were supplied by general, orthopedic, and plastic surgeons. The authors evaluated all soft-tissue injuries managed at the hospital and assessed the need for plastic surgery services in a crisis intervention field hospital. Information was gathered regarding soft-tissue injuries throughout the activity of the hospital. In addition, patients' charts, operations' reports, and entry and evacuation logs were reviewed for all patients accepted and treated in the field hospital. Interviews of patients, local physicians, and citizens of Adapazari were performed to evaluate the medical situation in the first 3 days after the earthquake. A total of 1205 patients were treated by the field hospital in Adapazari; 138 (11.45 percent) of these patients sought aid for isolated soft-tissue injuries, 105 of which (76.09 percent) were earthquake-related. Twenty (51.28 percent) of the operations performed in the hospital were to treat soft-tissue injuries; 1.49 percent of all patients underwent minor surgical manipulations by the plastic surgeon on staff. Plastic surgery patients occupied 13.6 percent of the hospital beds. In conclusion, the authors find it beneficial to supply plastic surgery services at a field hospital in an earthquake situation.

In vitro model of intravenous fluid administration: analysis of vein resistance to rapid fluid delivery.

Rapid fluid administration is the cornerstone of successful trauma resuscitation of patients in a state of shock. Intravenous (IV) fluid delivery is a physical intrusion into a vein which results in a complex interaction between the rigid catheter and the compliant vein. We present an experimental model of IV infusion into a vein-like compliant tube that (a) demonstrated the interdependence between fluid administration and blood flow in a compliant tube and (b) allowed investigation of the contribution of the central venous system (between the infusion site and the heart) to the total resistance to infusion flow rate. The results show that in cases with very high resistance in the central venous system a significant increase of infusion flow rate cannot be achieved just by increasing the infusion pressure. Similarly, in cases of small veins when only small catheters can be used, infusate flow rate may be increased only by using two independent infusion ports. In cases with increased tissue pressure due to edema, gravity-driven infusion may not produce sufficient perfusion of the vascular compartments. It was also shown that the vein valves do not always close, and that peripheral blood flow may continue together with the infusate fluid (e.g., when there is a small downstream resistance and infusion with a small catheter).

An international training program to assist with establishing emergency medicine in Ethiopia.

Ethiopia has a population of 56 million and an area of 1,110,000 km(2). Ethiopia is one of the poorest nations in the world, and its health services system reflects that poverty. Accidental injury, violence, infectious diseases, and natural and manmade disasters abound, yet emergency medicine is practically nonexistent. Poorly equipped and staff emergency "rooms" supply substandard service even in the capital. Significant work and planning are under way by a group of high-quality and dedicated local physicians and nurses with international support from Israel and the United States. A coherent plan is due at the end of the year. Much financial and professional support from outside sources will be required for significant advances in the quality of emergency care to improve. Human as well are material resources are vital.

Isoflurane and sodium nitroprusside reduce the depressant effects of protamine sulfate on isolated ischemic rat hearts.

UNLABELLED: The administration of protamine sulfate (protamine) to reverse the action of heparin is associated with adverse reactions. We studied the effects of protamine and isoflurane on isolated, perfused rat hearts previously subjected to cardioplegic ischemia. Hearts were perfused with oxygenated Krebs-Henseleit (KH) solution for 30 min, then subjected to cardioplegic ischemia for 30 min (KCl 16 mEq/L at 31 degrees C) and 5 min reperfusion. Drug exposure lasted 15 min, and the recovery period was 60 min. Test groups were control, protamine (10 microg/mL), isoflurane (1.5%), protamine +/- isoflurane, sodium nitroprusside (SNP) (2.5 ng/mL), and SNP +/- protamine. Left ventricular developed pressure (LVP), coronary flow, and myocardial oxygen consumption were depressed by protamine to 30% +/- 4%, 47% +/- 4%, and 39% +/- 4% of baseline (P < 0.001 versus control), respectively. Isoflurane and SNP afforded partial protection from the effects of protamine: LVP was 57% +/- 5% and 51% +/- 3% of baseline, respectively (P < 0.05 versus protamine alone and control); coronary flow was 70% +/- 6% and 97% +/- 12% of baseline, respectively (P < 0.05 versus protamine alone; P < 0.05 for isoflurane versus control); and O2 consumption was 69% +/- 6% and 88% +/- 15% of baseline, respectively (P < 0.05 versus protamine; P < 0.05 for isoflurane versus control). In this model, protamine-induced myocardial depression and coronary vasoconstriction were less pronounced in the presence of either isoflurane or SNP. IMPLICATIONS: We examined the interactions of isoflurane, sodium nitroprusside, and protamine in a rat heart model and found that both isoflurane and sodium nitroprusside partially protect the heart from the depressant effects of protamine. This finding is significant, as these drugs are often used in heart surgery.

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.

[Severe heat stroke in an intensive care unit: course of the disease in the intensive care unit, and early and subsequent treatment results].

During the August 1998 heat wave in Tel Aviv we admitted many patients for acute heat-related illness; 6 had severe heat stroke and were admitted in critical condition. We describe their clinical courses during the first 5 days of hospitalization, including response to treatment and implications for future management of this disorder. The mean APACHE II score of the 6 was 30 +/- 3.5 and mean Glasgow Coma Scale rating 3.5 +/- 0.5; they were in hypovolemic shock and respiratory failure, necessitating mechanical ventilation. Despite early effective therapy (core temperature in all was reduced to less than 39 degrees C in less than 1 hour), there was 1 death (mortality 15%) and 4 required further intensive care for life-threatening multiple organ failure. During severe heat waves a significant number of referrals for acute heat-related illness must be anticipated, possibly overwhelming admission capacity of regional intensive-care units. Severe heat stroke complicated by multi-organ failure is not necessarily related to prior physical activity. Although important in determining prognosis, early treatment does not prevent severe complications. Mechanisms regulating body heat may remain disturbed for days following early treatment and apparent stabilization, mandating continued hospitalization.

[Injuries due to falls in urban buses: 100 consecutive cases].

We reviewed the charts of 100 consecutive emergency department (ED) cases of injuries in public buses (not due to actual traffic accidents) seen during 7 months in 1995. There were 29 males and 71 females with a mean age of 55.6 +/- 21.4 years, median 60, and range 13-91. 92 were discharged home directly from the ED. 3 were admitted to general surgical wards, and 1 each to the orthopedic, medical and neurosurgical wards, while 2 soldiers were sent for observation to a military clinic. There were 28 spinal column, 27 head and 25 chest injuries; 1 patient died. There were no significant differences in admissions during the months of the year. 58% of injuries occurred during normal working hours, with a peak incidence at about 1000 hrs. The most common cause was falling while standing, due to sudden acceleration/deceleration or sharp turns. There are 1900 buses in Tel Aviv which carry 1.1 million passengers daily and most of which are capable of significant acceleration. A high proportion of passengers travel standing, and elderly passengers are more liable to fall when the bus accelerates, decelerates or turns. We calculate a potential national yearly bus injury toll from falls of more than 1000, which often result in significant morbidity and even mortality. A national survey is now being planned.

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.

Gut decontamination reduces bowel ischemia-induced lung injury in rats.

OBJECTIVE: To evaluate the effects of gut decontamination on endotoxin, tumor necrosis factor (TNF) levels, and the associated lung injury in a rat model of bowel ischemia. SUMMARY BACKGROUND DATA: Gut ischemia induces disruption of the intestinal mucosal barrier, allowing translocation of bacteria and endotoxin into the blood, which may trigger a systemic inflammatory response and lung injury. METHODS: Thirty anesthetized rats were randomized into three groups: (1) ischemia-reperfusion (I/R) alone (a 60-min superior mesenteric artery occlusion and 4 h of reperfusion, n=10); (2) rats that underwent gut decontamination prior to ischemia (I/R+GD, n=10); and (3) control rats (sham operated, n=10). Serum levels of lipopolysaccharide (LPS) and TNF were measured at the end of the experiment. Lung permeability was measured using bovine serum albumin labeled with 125I, and organ injury was assessed histologically. RESULTS: One hour of bowel ischemia and 4 h of reperfusion (I/R) led to elevations of blood LPS and TNF levels of 0.33+/-0.005 EU/mL and 173+/-56 pg/mL, which were higher than the sham group (p<0.01). Gut decontamination (I/R+GD) significantly attenuated the LPS and TNF generation, 0.09+/-0.005 and 56.2+/-6 pg/mL (p<0.01). Lung injury as assessed by pulmonary permeability index was also reduced by gut decontamination, 2.1+/-0.42 vs 5.3+/-0.82 in the control group (p<0.03). Surprisingly no difference was detected in the number of pulmonary neutrophils in sequestration between the groups. CONCLUSIONS: Our data suggest that gut decontamination can reduce the generation of LPS, TNF, and the severity of lung damage that often follows ischemia and reperfusion of the intestine in rats.

Effects on pulmonary function of daily exposure to dry or humidified hyperbaric oxygen.

The purpose of this study was to examine the effects of breathing dry or humidified hyperbaric oxygen on pulmonary function. Pulmonary function tests were performed before and after each of 10 hyperbaric oxygen exposures at 2.5 atmospheres absolute (ATA) for 95 min in a group of 13 patients treated daily by hyperbaric oxygen for problem wounds. Patients breathed dry oxygen during five successive sessions and humidified oxygen during the remaining five. No differences were found between forced vital capacities (FVC) and maximal expiratory flows before and after hyperbaric oxygen exposure while breathing dry or humidified oxygen. Significant differences were found for the changes in the percentage of FVC expired in 1 s (FEV1%) and mean forced mid-expiratory flow rate during the middle half of the FVC (FEF25-75%) on day 1 alone: decrements of 1.42 and 2.96%, respectively, under dry oxygen, vs. increments of 3.93 and 34.4%, respectively, for humidified oxygen. Day-to-day decrements in the percent changes in FEV1% and FEF25-75% were observed while breathing humidified hyperbaric oxygen. These results demonstrate that repeated daily exposure to humidified hyperbaric oxygen abolishes the initial beneficial effect of humidification on peripheral airways flow characteristics.

The isolated post ischaemic rat heart is more vulnerable to protamine sulphate than the non-ischaemic heart.

Protamine sulphate is currently used for the reversal of heparin anticoagulation but is known to cause direct myocardial depression. The purpose of this study was to compare the effects of protamine sulphate on the isolated heart with and without cardioplegic ischaemia. Isolated rat hearts (Langendorff preparation) were electrically paced at 300 beats/min and perfused with Krebs-Henseleit solution. Five groups were tested: (1) control: no ischaemia, no protamine; (2) no ischaemia, protamine; (3) no ischaemia, protamine (time-matched control to groups 4 and 5); (4) control: ischaemia, no protamine; and (5) ischaemia, protamine. Protamine sulphate was infused for 15 min at 10 microg/ml. In groups 4 and 5, cardioplegic ischemia was maintained for 30 min at 30 degrees C before protamine exposure. Protamine decreased myocardial performance in a time- and dose-dependent manner. Protamine depressed mean (s.d.) myocardial left ventricular pressure in both non-ischaemic hearts (groups 2 and 3, to 49(4)% and 50(4)% from baseline, respectively) and post ischaemic hearts (group 5, to 28(8%). Mean (s.d.) left ventricular-developed pressure only partially recovered after protamine in post-ischaemic hearts (to 55(13)% of baseline) compared with full recovery of the non-ischaemic group. Protamine depressed coronary flow to 70(5)% and 74(8)% in non-ischaemic hearts (groups 2 and 3, respectively) and to 58(7)% in group 5. Coronary flow recovered completely at the end of the experiments in all protamine-treated groups. In conclusion, isolated rat hearts subjected to cardioplegic ischaemia are more vulnerable to protamine than are non-ischaemic hearts.

Midazolam versus propofol for long-term sedation in the ICU: a randomized prospective comparison.

OBJECTIVE: To compare the efficacy, safety, and cost of midazolam and propofol in prolonged sedation of critically ill patients. DESIGN: Randomized, prospective study. SETTING: General intensive care unit (ICU) in a 1100-bed teaching hospital. PATIENTS: 67 critically ill, mechanically ventilated patients. INTERVENTIONS: Patients were invasively monitored and mechanically ventilated. A loading dose [midazolam 0.11 +/- 0.02 (SEM) mg.kg-1, propofol 1.3 +/- 0.2 mg.kg-1] was administered, followed by continuous infusion, titrated to achieve a predetermined sedation score. Sedation was continued as long as clinically indicated. MEASUREMENTS AND RESULTS: Mean duration of sedation was 141 and 99 h (NS) for midazolam and propofol, respectively, at mean hourly doses of 0.070 +/- 0.003 mg.kg-1 midazolam and 1.80 +/- 0.08 mg.kg-1 propofol. Overall, 68% of propofol patients versus 31% of midazolam (p < 0.001) patients had a > 20% decrease in systolic blood pressure after the loading dose, and 26 versus 45% (p < 0.01) showed a 25% decrease in spontaneous minute volume. Propofol required more daily dose adjustments (2.1 +/- 0.1 vs 1.4 +/- 0.1, p < 0.001). Nurse-rated quality of sedation with midazolam was higher (8.2 +/- 0.1 vs 7.3 +/- 0.1 on a 10-cm visual analog scale, p < 0.001). Resumption of spontaneous respiration was equally rapid. Recovery was faster after propofol (p < 0.02), albeit with a higher degree of agitation. Amnesia was evident in all midazolam patients but in only a third of propofol patients. The cost of propofol was 4-5 times higher. CONCLUSIONS: Both drugs afforded reliable, safe, and controllable long-term sedation in ICU patients and rapid weaning from mechanical ventilation. Midazolam depressed respiration, allowed better maintenance of sedation, and yielded complete amnesia at a lower cost, while propofol caused more cardiovascular depression during induction.

Administration of amphotericin B in lipid emulsion decreases nephrotoxicity: results of a prospective, randomized, controlled study in critically ill patients.

OBJECTIVES: To evaluate the differences in efficacy and in clinical and biochemical tolerance to amphotericin B administered in a lipid emulsion compared with amphotericin B administered in 5% dextrose in water in the treatment of Candida albicans infection in intensive care unit (ICU) patients. DESIGN: Prospective, controlled, randomized study, conducted during a 2.5-yr period, comparing the two treatment protocols. SETTING: General ICU of a university-affiliated municipal hospital. PATIENTS: Sixty consecutive critically ill patients with confirmed or suspected Candida infection. INTERVENTIONS: Patients received amphotericin B (1 mg/kg/24 hrs), administered randomly in 5% dextrose in water (group A), or in lipid emulsion (20% intralipid) (group B). MEASUREMENTS AND MAIN RESULTS: Clinical tolerance (fever, chills, hemodynamics), hepatorenal tolerance, and biological tolerance (serum electrolytes and coagulation profile) were evaluated. Patients receiving amphotericin B in lipid emulsion experienced a lower frequency rate of drug-associated fever (61.4% vs. 5.8%, p < .003) rigors (54% vs. 8.5%, p < .004), hypotension (17% vs. 0%), and nephrotoxicity (increase of serum creatinine concentration 66.7% vs. 20%, p < .0002). Significant (264,500 +/- 71,460 to 163,570 +/- 34,450 mm3, p < .01) thrombocytopenia, not associated with active bleeding, occurred in patients receiving amphotericin B lipid in emulsion but not in patients receiving the drug in dextrose. CONCLUSIONS: Treatment with amphotericin B in a lipid emulsion when given to critically ill patients with Candida sepsis seems to be safer and as effective as the conventional mode of administration.

Use of flumazenil in the treatment of drug overdose: a double-blind and open clinical study in 110 patients.

OBJECTIVES: To assess the efficacy, usefulness, safety, and dosages of flumazenil required when flumazenil is used in the diagnosis of benzodiazepine-induced coma (vs. other drug-induced coma), and to reverse or prevent the recurrence of unconsciousness. DESIGN: A two-phase study: a controlled, randomized, double-blind study followed by a prospective, open study. SETTING: An 800-bed, teaching, university-affiliated hospital. PATIENTS: Unconscious patients (n = 110) suspected of benzodiazepine overdose, graded 2 to 4 on the Matthew and Lawson coma scale, were treated with flumazenil, the specific benzodiazepine receptor antagonist. The first 31 patients were studied in a double-blind fashion, while the rest of the patients were given flumazenil according to an open protocol. INTERVENTIONS; All patients received supplemental oxygen; endotracheal intubation was performed, and synchronized intermittent mandatory ventilation was initiated whenever it was deemed necessary. A peripheral intravenous cannula was inserted, as were indwelling arterial and urinary bladder catheters. Blood pressure, electrocardiogram, respiratory rate, end-tidal CO2, and core temperature were continuously monitored. The first 31 double-blind patients received either intravenous flumazenil (to a maximum of 1 mg) or saline, while the rest of the patients were given flumazenil until either regaining consciousness or a maximum of 2.5 mg was injected. Patients remaining unconscious among double-blind patients or those patients relapsing into coma after the first dose were later treated in the open phase of the study. Treatment continued by boluses or infusion as long as efficacious. MEASUREMENTS AND MAIN RESULTS: Fourteen of 17 double-blind, flumazenil-treated patients woke after a mean of 0.8 +/- 0.3 (SD) mg vs. one of 14 placebo patients (p < .001). Seventy-five percent of the aggregated controlled and uncontrolled patients awoke from coma scores of 3.1 +/- 0.6 to 0.4 +/- 0.5 (p < .01) after the injection of 0.7 +/- 0.3 mg of flumazenil. These patients had high benzodiazepine serum blood concentrations. Twenty-five percent of the patients did not regain consciousness. These patients had very high serum concentrations of nonbenzodiazepine drugs. Sixty percent of the responders who had primarily ingested benzodiazepines remained awake for 72 +/- 37 mins after flumazenil administration; 40% relapsed into coma after 18 +/- 7 mins and various central nervous system depressant drugs were detected in their blood in addition to benzodiazepines. Seventy-one percent of the patients had ingested tricyclic antidepressants. Seventy-eight percent of the responders were continually and efficaciously treated for < or = 8 days. Fourteen (25%) of the intubated patients were extubated safely while 12 patients, who had shown increased respiratory insufficiency, resumed satisfactory respiration after flumazenil injection. Five cases of transient increase in blood pressure and heart rate were encountered. There were 27 mildly unpleasant "waking" episodes, such as anxiety, restlessness, and aggression, but no patient had benzodiazepine withdrawal signs, convulsions, or dysrhythmia, most noticeably absent in tricyclic antidepressant-intoxicated patients. CONCLUSIONS: Flumazenil is a valid diagnostic tool for distinguishing pure benzodiazepine from mixed-drug intoxication or nondrug-induced coma. Flumazenil is effective in preventing recurrence of benzodiazepine-induced coma. Respiratory insufficiency is reversed after its administration. Flumazenil is safe when administered cautiously, even in patients with coma caused by a mixed overdose of benzodiazepine plus tricyclic antidepressants.