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Biomedical subjects

G Bar-Joseph

Publications and source records attributed to G Bar-Joseph.

At least 19 recordsLinked to original sources

Improved resuscitation outcome in emergency medical systems with increased usage of sodium bicarbonate during cardiopulmonary resuscitation.

BACKGROUND: The use of sodium bicarbonate (SB) in cardiopulmonary resuscitation (CPR) is controversial. This study analyzes the effects of SB use on CPR outcome in the Brain Resuscitation Clinical Trial III (BRCT III), which was a multicenter randomized trial comparing high-dose to standard-dose epinephrine during CPR. Sodium bicarbonate use in BRCT III was optional. METHODS: The entire BRCT III database was reviewed. Analysis included only patients who arrested out of the hospital and whose time from collapse to initiation of ACLS was no longer than 30 min (total n = 2122 patients). Sodium bicarbonate use by the 16 participating study sites was analyzed. The study sites were divided according to their SB usage profile: 'low SB user' sites administered SB in less than 50% of CPRs and their first epinephrine to SB time exceeded 10 min; and 'high SB user' sites used SB in over 50% of CPRs and their first epinephrine to SB time was <10 min. RESULTS: Sites' SB usage rates ranged between 3.1% and 98.2% of CPRs. Sodium bicarbonate usage rates correlated inversely with the sites' intervals from collapse (r = - 0.579 P = 0.018) from initiation of ACLS (r = - 0.685 P = 0.003) and from first epinephrine (r = - 0.611 P = 0.012) to SB administration. Mean ROSC rate in the 'high SB user' sites was 33.5% (CI = 30.0-37.0) compared to 25.7% (CI = 23.1-28.4) in the 'low SB user' sites. In the 'high SB user' sites, hospital discharge rate was 5.3% (CI = 3.6-7.0) compared to 3% (CI = 2.0-4.0) in the 'low SB user' sites, and 5.3% (CI = 3.6-7.0) had a favorable neurological outcome compared to 2.1% (CI = 1.2-3.0) in the 'low SB user' sites. Collapse to ACLS interval was 8.5 min (CI = 8.1-9.0) in the 'high SB user' sites compared to 10.2 min (CI = 9.8-10.6) in the 'low SB user' sites, and their ACLS to first epinephrine interval was 7.0 min (CI = 6.5-7.5) compared to 9.7 min (CI = 9.3-10.2). Multivariate regression analysis found that belonging to 'high SB user' sites independently increased the chances for ROSC (OR 1.36, CI 1.08-1.7) and for achieving a good neurological outcome (OR 2.18, CI 1.23-3.86). CONCLUSIONS: Earlier and more frequent use of SB was associated with higher early resuscitability rates and with better long-term outcome. Sodium bicarbonate may be beneficial during CPR, and it should be subjected to a randomized clinical trial.

Acidosis↗

The use of external fixators in the immobilization of pediatric fractures.

The use of external fixation in the immobilization of diaphyseal and metaphyseal fractures in children is still controversial, as these fractures are generally managed by immediate plaster casting, by traction followed by casting, by various methods of internal fixation, including the recently developed flexible rods, and by plating. Between 1982 and 1998, we treated 64 children with fractures of the long bones of the lower limb using external fixation, 44 of whom were available for follow-up (46 fractures). Their average age on the day of injury was 8.l years. Average follow-up extended for 4 years. The external fixation used was left in place for an average of 67 days. Full range of movement was achieved in 42 children (44 limbs). The longitudinal axis was anatomically correct (<5 degrees angulation) in 40 children (42 limbs). Due to malalignment of the fracture (15 degrees varus) in one child, tibial osteotomy was performed 4 years after fracture healing. There was no leg length discrepancy in 38 children, and shortening of >2 cm was measured in the fractured limbs of 2 children. We found the use of external fixators to be easy, quick, with a short learning curve, and appropriate for comminuted and closed fractures of the long bones, and especially for children with polytrauma.

Adolescent↗

Plasmapheresis in a very young infant with atypical hemolytic uremic syndrome.

Atypical hemolytic uremic syndrome (HUS) is a heterogeneous group of disorders, the pathogenesis of which is unclear. Plasma transfusions and plasmapheresis are widely used modes of therapy for adults with this life-threatening syndrome. There is very limited experience in using plasmapheresis therapy in children and infants with atypical HUS. Plasmapheresis, which is considered a relatively safe procedure in adults and older children, may be hazardous in neonates and very young infants and can result in severe complications. We report a 2-month-old infant with idiopathic atypical HUS, who was successfully treated with a 1-month course of plasmapheresis during the acute phase of the disease. Appropriate preparations as well as several adjustments were made in order to meet the special needs of this very young infant who, to the best of our knowledge, is the youngest reported patient with atypical HUS to undergo plasmapheresis. Plasmapheresis therapy of the infant was not associated with any complications of the procedure and resulted in marked clinical improvement. We conclude that plasmapheresis in neonates and in very small infants is technically feasible, can be performed without major complications, and may be of benefit in individual cases.

Feasibility Studies↗

Abdominal compartment syndrome in children.

OBJECTIVE: To investigate the frequency, predisposing factors, clinical presentation, and outcome of abdominal compartment syndrome (ACS) in critically ill pediatric patients. DESIGN: A prospective study over a 5-yr period. SETTING: Pediatric intensive care unit of a tertiary care, university hospital. PATIENTS: All patients admitted to the pediatric intensive care unit were screened for the presence of ACS and were treated with a uniform protocol. ACS was defined as abdominal distention with intra-abdominal pressure (IAP) > 15 mm Hg, accompanied by at least two of the following: oliguria or anuria; respiratory decompensation; hypotension or shock; metabolic acidosis. MEASUREMENTS AND MAIN RESULTS: Of 1762 patients admitted over 5 yrs, ten patients (0.6%) had a total of 15 episodes of ACS. Of 406 trauma cases, three had ACS (0.7%). Three of the ten patients had primary abdominal conditions (mesenteric vein thrombosis, intussusception, enterocolitis), three had abdominal surgery (trauma, Kasai operation, esophageal perforation and peritonitis), three had primary central nervous system involvement, and one had meningococcemia. At laparotomy, bowel ischemia or necrosis was found in four episodes of ACS (27%). Mean IAP at diagnosis of ACS was 23.9 +/- 3.8 (range 17-31) mm Hg. Physiologic parameters were compared during 4 hrs before the development of ACS, during ACS, and after abdominal decompression. Mean arterial pressure, Pao(2), Pao(2)/Fio(2) ratio, and urinary output decreased significantly, whereas Paco(2), peak inspiratory pressures, positive end-expiratory pressures, and base deficit increased significantly after the development of ACS. After decompressive laparotomy, the condition of the patients improved promptly and these variables returned to pre-ACS values. Overall mortality rate in this group was 60%. CONCLUSIONS: Although relatively infrequent compared with adults, ACS occurs in critically ill children. Timely decompression of the abdomen results in uniform improvement, but overall mortality is still high. In contrast with adults, children with ACS have diverse primary diagnoses, with a significant number of primary extra-abdominal-mainly central nervous system-conditions. Ischemia and reperfusion injury appear to be the major mechanisms for development of ACS in children. Clinical presentation is similar to adults, but children may develop ACS at a lower IAP (as low as 16 mm Hg).

Journal Article↗

Response to repeated equal doses of epinephrine during cardiopulmonary resuscitation in dogs.

STUDY OBJECTIVE: Advanced cardiac life support (ACLS) guidelines recommend a 3- to 5-minute interval between repeated doses of epinephrine. This recommendation does not take into account the dose of epinephrine used, and only very limited data exist regarding the hemodynamic responses to repeated "high" doses of epinephrine. The objective of this study was to analyze the hemodynamic responses to repeated, equal, high doses of epinephrine administered during cardiopulmonary resuscitation (CPR) in a canine model of ventricular fibrillation (VF). METHODS: This study used a secondary analysis of data collected in a prospective, randomized study, primarily designed to assess the effects of acid buffers in a canine model of cardiac arrest. VF was electrically induced. After 10 minutes, CPR was initiated, including ventilation with FIO(2)=1.0, external chest compressions, administration of epinephrine (0.1 mg/kg repeated every 5 minutes) and defibrillation. Animals were randomized to receive either NaHCO(3), Carbicarb, tromethamine (THAM), or NaCl. The hemodynamic variables were sampled from each experiment's paper chart at 1-minute intervals, and the responses to the first 4 doses of epinephrine were compared. RESULTS: Thirty-six animals (9 in each buffer group) were included in this analysis. Systolic, diastolic, and coronary perfusion pressures increased steeply (by 100%, 130%, and 190%, respectively) only after the first epinephrine dose. These pressures peaked at 2 to 3 minutes and decreased only slightly and insignificantly during the rest of the 5-minute interval, until the next epinephrine dose. No further significant increases in arterial pressures were observed in response to the next 3 doses of epinephrine, administered 5 minutes apart. CONCLUSION: The hemodynamic effects of high-dose epinephrine (0.1 mg/kg) during CPR appear to last longer than 5 minutes. Therefore, longer intervals between doses may be justified with high doses of epinephrine.

Adrenergic alpha-Agonists↗

Hospitalizations due to falls in Jewish and Arab children in northern Israel.

In Israel, there are no epidemiological data regarding nonfatal childhood falls. A retrospective survey was conducted in order to find epidemiological characteristics of childhood falls among the different populations of northern Israel. During the years 1993 through 1995, 3082 children were hospitalized in Rambam Medical Center (RMC) due to injury. The children were subdivided into the four main populations: Jewish and Arab residents of Haifa region (the main metropolitan area) and Jewish and Arab residents of the Galilee region (the rural region). All of the children who suffered injury that required mechanical ventilation and careful assessment were admitted to the PICU. The charts of the children admitted to the PICU were then further studied. The demographic characteristics of all the cases of falls were statistically analyzed and the annual admission rates due to falls were calculated using the national statistical registrations of children in Israel. Falls were responsible for 1049 admissions due to injury, one third of the total number of children who were admitted due to an injury. Most of the children were five years of age or younger. Two thirds of the total childhood falls were of Arabs. The majority of the admissions were of two major sub-populations of northern Israel: Arab residents of Galilee region (66%) and Jewish residents of Haifa region (34%). Higher admission rate was found among Arab children of the Western Galilee district in comparison with Jewish children of the Haifa district. Most of the children who were admitted to the PICU were Arabs: nearly all of these children were from the rural region. More Arab than Jewish children who fell were admitted to the PICU and the majority of these cases were falls from buildings (private houses). Arab children of the rural region were responsible for 95% of the cases. These falls were mainly in staircases (46%) and from balconies (21%), roofs (11%) and windows (11%). The findings of the present study suggest that young Arab rural children in northern Israel are at high risk to a severe injury due to fall. Possible causes are discussed and a preventative intervention is suggested.

Accidental Falls↗

Comparison of sodium bicarbonate, Carbicarb, and THAM during cardiopulmonary resuscitation in dogs.

OBJECTIVES: During cardiopulmonary resuscitation (CPR), elimination of CO2 was shown to be limited by low tissue perfusion, especially when very low perfusion pressures were generated. It has therefore been suggested that sodium bicarbonate (NaHCO3), by producing CO2, might aggravate the hypercarbic component of the existing acidosis and thereby worsen CPR outcome. The objectives of this study were to evaluate the effects of CO2 producing and non-CO2 producing buffers in a canine model of prolonged ventricular fibrillation followed by effective CPR. DESIGN: Prospective, randomized, controlled, blinded trial. SETTING: Experimental animal research laboratory in a university research center. SUBJECTS: Thirty-eight adult dogs, weighing 20 to 35 kg. INTERVENTIONS: Animals were prepared for study with thiopental followed by halothane, diazepam, and pancuronium. Ventricular fibrillation was electrically induced, and after 10 mins, CPR was initiated, including ventilation with an FIO2 of 1.0, manual chest compressions, administration of epinephrine (0.1 mg/kg every 5 mins), and defibrillation. A dose of buffer, equivalent to 1 mmol/kg of NaHCO3, was administered every 10 mins from start of CPR. Animals were randomized to receive either NaHCO3, Carbicarb, THAM, or 0.9% sodium chloride (NaCl). CPR was continued for up to 40 mins or until return of spontaneous circulation. MEASUREMENTS AND MAIN RESULTS: Buffer-treated animals had a higher resuscitability rate compared with NaCl controls. Spontaneous circulation returned earlier and at a significantly higher rate after NaHCO3 (in seven of nine dogs), and after Carbicarb (six of ten dogs) compared with NaCl controls (two of ten dogs). Spontaneous circulation was achieved twice as fast after NaHCO3 compared with NaCl (14.6 vs. 28 mins, respectively). Hydrogen ion (H+) concentration and base excess, obtained 2 mins after the first buffer dose, were the best predictors of resuscitability. Arterial and mixed venous Pco2 did not increase after NaHCO3 or Carbicarb compared with NaCl. CONCLUSIONS: Buffer therapy promotes successful resuscitation after prolonged cardiac arrest, regardless of coronary perfusion pressure. NaHCO3, and to a lesser degree, Carbicarb, are beneficial in promoting early return of spontaneous circulation. When epinephrine is used to promote tissue perfusion, there is no evidence for hypercarbic venous acidosis associated with the use of these CO2 generating buffers.

Animals↗

Clostridium septicum infection in children with cyclic neutropenia.

Atraumatic Clostridium septicum infection is rare in infancy and childhood and is associated with a high mortality rate. Although in adults it has been reported to occur mainly in patients with gastrointestinal malignancy, pediatric cases were always associated with neutropenia. About 70% of the cases were described in children with neutropenia caused by chemotherapy and 30% were found in children with cyclic neutropenia. No case was described in children with other forms of congenital severe neutropenia. We describe three children with cyclic neutropenia and severe Clostridium septicum infection, discuss the various possibilities of causation, and the need for prompt and aggressive treatment of this serious condition.

Abdominal Muscles↗

Future directions for resuscitation research. IV. Innovative advanced life support pharmacology.

The topics discussed in this session include a partial review of laboratory and clinical studies examining the effects of adrenergic agonists on restoration of spontaneous circulation after cardiac arrest, the effects of varying doses of epinephrine, and the effects of novel vasopressors, buffer agents (NaHCO3, THAM, 'Carbicarb') and anti-arrhythmics (lidocaine, bretylium, amiodarone) in refractory ventricular fibrillation. Novel therapeutic approaches include titrating electric countershocks against electrocardiographic power spectra and of preceding the first countershocks with single or multiple drug treatments. These approaches need to be investigated further in controlled animal and patient studies. Epidemiologic data from randomized clinical outcome studies can give clues, but cannot document pharmacologic mechanisms in the dynamically changing events during attempts to achieve restoration of spontaneous circulation from prolonged cardiac arrest. Also, rapid drug administration by the intraosseous route was compared with intratracheal and intravenous (i.v.) drug administration. Many studies on the above treatments have yielded conflicting results because of differences between healthy hearts of animals and sick hearts of patients, differences in arrest (no-flow) times and cardiopulmonary resuscitation (CPR) (low-flow) times, different pharmacokinetics, different dose/response requirements, and different timing of drug administration during low-flow CPR versus during spontaneous circulation. The need to stabilize normotension and prevent rearrest by titrated novel drug administration, once spontaneous circulation has been restored, requires research. Most of the above topics require some re-evaluation in clinically realistic animal models and in cardiac arrest patients, especially by titration of old and new drug treatments against variables that can be monitored continuously during resuscitation.

Adrenergic Agonists↗

Cerebral resuscitation from cardiac arrest: treatment potentials.

In 1961, in Pittsburgh, PA, "cerebral" was added to the cardiopulmonary resuscitation system (CPR --> CPCR). Cerebral recovery is dependent on arrest and cardiopulmonary resuscitation times, and numerous factors related to basic, advanced, and prolonged life support. Postischemic-anoxic encephalopathy (the cerebral postresuscitation disease or syndrome) is complex and multifactorial. The prevention or mitigation of this syndrome requires that there be development and trials of special, multifaceted, combination treatments. The selection of therapies to mitigate the postresuscitation syndrome should continue to be based on mechanistic rationale. Therapy based on a single mechanism, however, is unlikely to be maximally effective. For logistic reasons, the limit for neurologic recovery after 5 mins of arrest must be extended to achieve functionally and histologically normal human brains after 10 to 20 mins of circulatory arrest. This goal has been approached, but not quite reached. Treatment effects on process variables give clues, but long-term outcome evaluation is needed for documentation of efficacy and to improve clinical results. Goals have crystallized for clinically relevant cardiac arrest-intensive care outcome models in large animals. These studies are expensive, but essential, because positive treatment effects cannot always be confirmed in the rat forebrain ischemia model. Except for a still-elusive breakthrough effect, randomized clinical trials of CPCR are limited in their ability to statistically document the effectiveness of treatments found to be beneficial in controlled outcome models in large animals. Clinical studies of feasibility, side effects, and acceptability are essential. Hypertensive reperfusion overcomes multifocal no-reflow and improves outcome. Physical combination treatments, such as mild resuscitative (early postarrest) hypothermia (34 degrees C) plus cerebral blood flow promotion (e.g., with hypertension, hemodilution, and normocapnia), each having multiple beneficial effects, achieved complete functional and near-complete histologic recovery of the dog brain after 11 mins of normothermic, ventricular fibrillation cardiac arrest. Calcium entry blockers appear promising as a treatment for postischemic-anoxic encephalopathy. However, the majority of single or multiple drug treatments explored so far have failed to improve neurologic outcome. Assembling and evaluating combination treatments in further animal studies and determining clinical feasibility inside and outside hospitals are challenges for the near future. Treatments without permanent beneficial effects may at least extend the therapeutic window. All of these investigations will require coordinated efforts by multiple research groups, pursuing systematic, multilevel research--from cell cultures to rats, to large animals, and to clinical trials. There are still many gaps in our knowledge about optimizing extracerebral life support for cerebral outcome.

Animals↗

Pathophysiologic and therapeutic implications of acid-base changes during CPR.

Acid-base changes occurring during cardiac arrest and subsequent CPR are related to a complex low-perfusion state characterized clinically by venous and tissue hypercarbic and metabolic (lactic) acidosis. This low-flow state is a dynamic process dependent on the time intervals between onset of arrest, initiation of CPR, and restoration of adequate spontaneous circulation. Increased release of CO2 from ischemic tissues and reduced CO2 transport from the tissues to the lungs result in profound tissue acidosis. However, recent experimental data suggest that even very low pH is compatible with neurologically intact survival. Thus, the clinical use of buffer agents, and especially of sodium bicarbonate, is currently controversial. Because results of controlled clinical studies are not available, a careful review of well-performed experimental studies is necessary. So far, the use of either CO2-generating or CO2-consuming buffers has not been proved conclusively to increase neurologically intact long-term survival after CPR. More importantly, adequate ventilation and effective chest compressions must be quickly established after cardiac arrest. This will counterbalance the hypercarbic and metabolic acidemia of cardiac arrest by creating concurrent hypocarbic arterial alkalemia during at least the early phase of CPR. Thus, the treatment of the complex acid-base changes associated with CPR is based primarily on the classical maneuvers of A and B (airway and breathing = adequate oxygenation and ventilation), C (chest compressions), and D (early defibrillation for rapid restoration of spontaneous circulation). In cases of prolonged cardiac arrest or preexisting metabolic acidemia, buffer therapy may be indicated.

Acid-Base Imbalance↗

Monkey model of severe volume-controlled hemorrhagic shock with resuscitation to outcome.

Seventeen cynomolgus monkeys under N2O analgesia and sedation were subjected to severe volume-controlled hemorrhagic shock (shed blood volume of 21 or 27 ml/kg). In 12 monkeys, resuscitation was started after increasing periods of hemorrhagic shock from 30 min to 5 h. In five additional monkeys, volume-controlled hemorrhage was modified at hemorrhagic shock 30 min to control MAP at 30 mmHg: resuscitation was started at hemorrhagic shock of 2 h. A clinically relevant resuscitation protocol consisted of a field phase from 0 to 6 h (lactated Ringer's solution, spontaneous breathing), and a hospital intensive care phase from 6 h to 48 h (blood, lactated Ringer's solution to mean arterial pressure (MAP) greater than or equal to 70 mmHg, controlled ventilation, advanced life support). Fifteen of the 17 monkeys survived. After outcome evaluation at 4 or 7 days, the eight monkeys with "moderate insult" had only transient functional impairment. Of the nine with "severe insult," three showed signs of moderate transient non-oliguric renal failure. Eight of the 12 monkeys studied morphologically showed scattered liver cell damage. None of the monkeys developed pulmonary dysfunction or functional or morphologic evidence of cerebral damage. This study establishes a new hemorrhagic shock-resuscitation model simulating field-to-hospital life support. Severe hemorrhagic shock with MAP 30-40 mmHg for 90-120 min (without trauma or sepsis) can lead to complete functional recovery after transient malfunction of liver and kidneys.

Animals↗