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Biomedical subjects

M Parr

Publications and source records attributed to M Parr.

At least 19 recordsLinked to original sources

Medical emergency teams: a role for expanding intensive care?

BACKGROUND: A high incidence of preventable adverse events and deaths in hospitals has triggered initiatives to improve the quality of care of acutely ill in-hospital patients. System changes involving the introduction of medical emergency teams, outreach services or rapid response teams are an integral part of these initiatives. The rationale for implementing a designated team is that early recognition and rapid institution of adequate therapy for the deteriorating patient can improve outcome. The concept of bringing intensive care expertise to any acutely ill patient irrespective of location within the hospital is envisioned as "critical care without walls". METHODS: Studies were identified by a PubMed search and cited references in key publications provided additional material including www-resources. More than 80 studies were identified and selected for review, however, no formal search strategy for a systematic review or meta-analysis was attempted. Only studies published in English were considered. RESULTS: Several non-randomized, before-and-after cohort studies demonstrate that implementation of medical emergency teams and equivalents can reduce the incidence of cardiac arrests, unexpected deaths, and unplanned intensive care admissions. However, one recent randomized, controlled trial of medical emergency teams failed to demonstrate any differences in outcomes. CONCLUSION: Several key operational issues need to be addressed before introducing medical emergency response teams based on current evidence. These issues include differences in healthcare systems and performance, patient case-mix, resources available, composition of the teams and calling criteria, and strategies for education, audit and governance.

Blood Circulation↗

Systemic capillary leak syndrome associated with compartment syndrome and rhabdomyolysis.

Systemic capillary leak syndrome (SCLS) is a rare disorder characterized by recurrent spontaneous episodes of hypovolaemic shock due to marked plasma shifts from the intravascular to the extravascular space. This presents as the characteristic triad of hypotension, haemoconcentration and hypoalbuminemia often with an associated monoclonal gammopathy. We describe a patient with SCLS who required aggressive fluid resuscitation and emergency fasciotomies for compartment syndrome with rhabdomyolysis. At presentation the patient was considered to have severe erythrocytosis and was therefore initially referred to a haematologist, which appears to be a frequent sequence of presentation for patients with SCLS. This patient also highlights the importance of muscle compartment pressure monitoring during volume resuscitation in patients with SCLS.

Acute Kidney Injury↗

Sequestration of adenoviral vector by Kupffer cells leads to a nonlinear dose response of transduction in liver.

Systemic administration of a recombinant adenovirus encoding the human interferon-beta gene (H5.110CMVhIFN-beta) results in transduction of hepatocytes and detectable circulating levels of IFN-beta protein. In preclinical studies in mice, we noticed a distinctly nonlinear dose response, with low levels of virus (1-3 x 10(10) viral particles) yielding barely detectable levels of IFN-beta but with a higher viral dose (1 x 10(11) particles) resulting in disproportionately high IFN-beta levels. Further studies showed that transgene expression levels from low viral doses could be dramatically enhanced by coadministering an unrelated recombinant adenovirus (H5.110CMVlacZ), suggesting that there was a viral dose threshold effect for efficient viral transduction and/or IFN-beta expression. This enhancement of reporter expression by a nonreporter adenovirus, effective upon coadministration, was further enhanced by preadministration of H5.110CMVlacZ (up to 8 h), but was ineffective if the helper virus was administered as little as 5 min after the H5.110CMVhIFN-beta reporter virus. Our data suggest that the reticuloendothelial system plays a role in this threshold effect, such that low doses of virus are efficiently taken up by the RES/Kupffer cells without leading to appreciable transgene expression, whereas high doses saturate these cells and are able to productively transduce hepatocytes. A better understanding of this phenomenon could have an impact on gene therapy clinical trial safety and efficacy.

Adenoviridae↗

"Recommendations for uniform reporting of data following major trauma--the Utstein style" (as of July 17, 1999). An International Trauma Anaesthesia and Critical Care Society (ITACCS).

Basic and advanced care of trauma patients has always been an important aspect of prehospital and immediate in-hospital emergency medicine, involving a broad spectrum of disciplines, specialties and skills delivered through Emergency Medical Services Systems which, however, may differ significantly in structure, resources and operation. This complex background has, at least in part, hindered the development of a uniform pattern or set of criteria and definitions. This in turn has hitherto rendered data incompatible, with the consequence that such differing systems or protocols of care cannot be readily evaluated or compared with acceptable validity. Guided by previous consensus processes evolved by the ERC, the AHA and other International Organizations--represented in ILCOR--on 'Uniform reporting of data following out-of-hospital and in-hospital cardiac arrest--the Utstein style' an international working group of ITACCS has drafted a document, 'Recommendations for uniform reporting of data following major trauma--the Utstein style'. The reporting system is based on the following considerations: A structured reporting system based on an "Utstein style template" which would permit the compilation of data and statistics on major trauma care, facilitating and validating independent or comparative audit of performance and quality of care (and enable groups to challenge performance statistics which did not take account of all relevant information). The recommendations and template should encompass both out-of-hospital and in-hospital trauma care. The recommendations and template should further permit intra- and inter-system evaluation to improve the quality of delivered care and identification of the relative benefits of different systems and innovative initiatives. The template should facilitate studies setting out to improve epidemiological understanding of trauma; for example such studies might focus on the factors that determine survival. The document is structured along the lines of the original Utstein Style Guidelines publication on 'prehospital cardiac arrest'. It includes a glossary of terms used in the prehospital and early hospital phase and definitions, time points and intervals. The document uses an almost identical scheme for illustrating the different process time clocks--one for the patient, one for the dispatch centre, one for the ambulance and, finally, one for the hospital. For clarity, data should be reported as core data (i.e. always obtained) and optional data (obtained under specific circumstances). In contrast to the graphic approach used for the Utstein template for pre- or in-hospital cardiac arrest, respectively, the present template introduces, for the time being, at least, a number of terms and definitions and a semantic rather than a graphic report form. The document includes the following sections: The Section Introduction and background The Section on Trauma Data Structure Development: presents a general outline of the development of structured data using object-orientated modelling (which will be discussed in due course) and includes a set of explanatory illustrations. The Section on Terms and Definitions: outlines terms and definitions in trauma care, describing different types of trauma (blunt, penetrating, long bone, major/combined, multiple/polytrauma and predominant trauma). The Section on Factors relating to the circumstances of the injury describes the following items: cause of injury (e.g. type of injury (blunt or penetrating), burns, cold, crush, laceration, amputation, radiation, multiple, etc. Severity of Injury e.g. prehospital basic abbreviated injury score developed by the working group. The score contains anatomical and physiological disability data, with the anatomical scale ranging ordinally from 1. Head to 9. External; the physiological disability scale ranging ordinally from 0--unsurvivable. Mechanism of injury recording for transportation incidents etc. e.g. the type of impact, po

Data Collection↗

The United Kingdom pre-hospital study of active compression-decompression resuscitation.

This prospective, controlled trial with crossover group design compares the effectiveness of active compression-decompression (ACD) cardiopulmonary resuscitation (CPR) and standard CPR on the outcomes of victims of prehospital cardiac arrest. In three UK cities, victims of non-traumatic, out of hospital cardiac arrest, over the age of 8 years received either standard or ACD-CPR on arrival of ambulance personnel. Main outcome measures were return of spontaneous circulation, survival to be admitted to the intensive care unit, survival to hospital discharge, and neurological outcome. A total of 576 patients (STD-CPR, n=309; ACD-CPR, n=267) were analysed. The treatment groups were similar with respect to age, gender, proportion of witnessed arrests, initial cardiac rhythm, and call to advanced life support interval. The proportion of patients receiving bystander CPR was higher in the ACD group (37.1% vs. 28.5%; P=0.028). The interval between collapse and defibrillation was longer in the ACD group (12.3 min vs. 10.4 min; P=0.028). There was no difference between the STD-CPR and ACD-CPR groups in survival to admission to the intensive care unit (13.6% vs. 13.8%; P=0.93) or hospital discharge (4.8% vs. 6.0%; P=0.67). There was no difference between the groups with respect to the neurological outcome of those patients surviving to hospital discharge. Analysis of important subgroups also showed no benefit for ACD-CPR. We conclude that there was no improvement in outcome with ACD-CPR when used by ambulance personnel in Cardiff and Portsmouth.

Aged↗

In vivo replication-deficient adenovirus vector-mediated transduction of the cytosine deaminase gene sensitizes glioma cells to 5-fluorocytosine.

Viral vector-mediated transfer of chemosensitization genes represents a promising new approach to the treatment of cancer. Previous reports have demonstrated that transfection of the bacterial cytosine deaminase (cd) gene into mammalian cells can sensitize them to the otherwise nontoxic nucleoside, 5-fluorocytosine (5-FC). We now report that a replication-deficient adenovirus vector that transduces the cd gene (Ad.CMV-cd) highly sensitizes 9L gliosarcoma cells to 5-FC, and that gene transduction is associated with a potent bystander effect that is not dependent on direct cell-to-cell contact. Stereotactic injection of Ad.CMV-cd into established rat gliomas, followed by systemic administration of 5-FC in vivo, results in prolongation of survival.

Adenoviruses, Human↗

Tidal volumes which are perceived to be adequate for resuscitation.

Observers trained in basic life support assessed chest rise in 34 patients who were anaesthetised and paralysed and whose lungs were being mechanically ventilated prior to routine surgery. Making 67 independent assessments, the observers indicated the tidal volume that they considered produced adequate chest rise for resuscitation. The mean tidal volume perceived to be adequate was 384 ml with 95% confidence limits of 362-406 ml. The perceived volumes correlated with the Body Mass Index. Guidelines by various authorities recommend that tidal volumes sufficient to make the chest rise normally should be used during resuscitation. The volumes perceived as adequate by the observers are much lower than the numerical values recommended by the American Heart Association (800-1200 ml). High tidal volumes are associated with an increased risk of gastric regurgitation in patients with an unprotected airway, CO2 delivery to the lungs is likely to be low during cardiac arrest obviating the need for high tidal volumes. In the light of present knowledge and the findings in this study, we would recommend that resuscitation training manikins are recalibrated to indicate satisfactory ventilation at tidal volumes of 400-600 ml. These volumes should reduce the risk of gastric inflation and permit more chest compressions to be carried out in a minute because the ventilation fraction of the CPR sequence is shorter. Adequate CO2 elimination should still be assured.

Adult↗

Liver function and morphology after resuscitation from severe hemorrhagic shock with hemoglobin solutions or autologous blood.

OBJECTIVE: To test the effects of three hemoglobin solutions on liver function and hepatic morphology after resuscitation from severe hemorrhagic shock. DESIGN: Prospective study. SETTING: Laboratory. SUBJECTS: Thirty-three beagle dogs. INTERVENTION: Hemorrhagic shock was induced in anesthetized dogs by removal of blood at a rate of 2 mL/kg/min until systolic blood pressure (BP) reached 50 mm Hg. BP was maintained at this level 2 hrs by further withdrawing 5 to 10 mL aliquots whenever BP increased > 50 mm Hg. Resuscitation was then initiated with autologous whole blood (n = 7), 4% pyridoxalated-hemoglobin-polyoxyethylene conjugate (4% PHP [n = 6]), 8% pyridoxalated-hemoglobin-polyoxyethylene conjugate (8% PHP [n = 9], or 8% stroma-free hemoglobin (n = 7). Four dogs were managed identically but were not resuscitated. Gross necropsy and histologic examination of the liver were performed on all dogs after 7 days, or earlier if death occurred. MEASUREMENTS AND MAIN RESULTS: In vitro interferences of PHP and stroma-free hemoglobin with liver function tests were determined and recommendations for interpretation of results from blood samples containing PHP and stroma-free hemoglobin were made. Blood was collected before, during, and after resuscitation from hemorrhagic shock. The dogs were then awakened and survivors were monitored daily with blood sampling until they were killed and necropsy was performed. After 7 days, the survival rate following hemorrhagic shock was 100% for whole blood and 4% PHP, 86% for stroma-free hemoglobin, and 33% for 8% PHP. Of the resuscitated dogs not surviving 7 days, all but one died within 27 hrs from coagulopathy. All dogs not resuscitated died within 1.75 hrs after 2 hrs of shock. Bilirubin, alkaline phosphatase, and lactic dehydrogenase concentrations could not be measured due to interferences of stroma-free hemoglobin and PHP. Aspartate (AST) and alanine (ALT) aminotransferase concentrations could be measured after dilution to overcome the interferences. Significant increases in AST and ALT values in all groups 24 hrs after resuscitation were attributed to hypoxic hepatocellular damage associated with the severity of the shock model rather than to the resuscitation fluid. Liver histology showed no changes attributed to toxic damage of hepatocytes in dogs resuscitated with stroma-free hemoglobin or PHP. However, changes, were less severe in dogs resuscitated with 4% PHP than in other groups. CONCLUSION: Morphologic studies at necropsy and liver function tests in dogs receiving hemoglobin solutions, compared with autologous blood, support the conclusion that the PHP and stroma-free hemoglobin solutions tested did not produce hepatic toxicity when used as resuscitation fluids in this model of severe shock.

Acute Disease↗

Oxygen transport and cardiovascular effects of resuscitation from severe hemorrhagic shock using hemoglobin solutions.

OBJECTIVE: To test the short-term efficacy of three hemoglobin solutions in restoring cardiac output, intravascular pressures, oxygen transport (DO2), and oxygen consumption (VO2) after resuscitation from severe hemorrhagic shock. DESIGN: Prospective study. SETTING: Research laboratory. SUBJECTS: Beagle dogs. INTERVENTIONS: After anesthesia and instrumentation, hemorrhagic shock was induced for 2 hrs by blood withdrawal to maintain systolic blood pressure at 50 mm Hg. Resuscitation then occurred with one of four different resuscitation fluids. One group of dogs was not resuscitated. Survival rate was monitored for 8 days. MEASUREMENTS AND MAIN RESULTS: In 33 beagle dogs, cardiovascular variables (DO2 and VO2) were compared after resuscitation with 8% stroma-free hemoglobin, 4% or 8% pyridoxalated-hemoglobin-polyoxyethylene conjugate (PHP44 and PHP88, respectively), or autologous whole blood. The dogs were anesthetized, paralyzed, mechanically ventilated (FIO2 of 0.21), and instrumented with arterial and pulmonary artery catheters. An average of 63% of estimated blood volume was removed to maintain systolic blood pressure at 50 mm Hg for 2 hrs. The dogs then were either not resuscitated (n = 4) or resuscitated with 8% stroma-free hemoglobin (n = 7), PHP44 (n = 6), PHP88 (n = 8), or whole blood (n = 8), with a volume equivalent to the withdrawn blood. Cardiovascular variables, DO2, VO2, oxygen extraction ratios, and blood concentrations of lactic acid and catecholamines were determined before, and for < or = 6 hrs after, resuscitation from hemorrhagic shock. Blood smears were microscopically examined. In addition, the survival rate was monitored for 8 days after resuscitation. By 2 hrs of hemorrhagic shock, there was a large decrease in DO2 (p < .05) and an increase in oxygen extraction ratio from 0.27 to 0.70 (p < .05). There was a 3.5-fold increase in lactate concentrations and a 25-fold increase in catecholamine concentrations as compared with preshock values. All dogs not resuscitated died within 1.75 hrs after 2 hrs of shock. After resuscitation with whole blood, all cardiovascular and oxygen transport variables returned to approximately prehemorrhage values and remained so throughout the measurement period. After resuscitation with any hemoglobin solution, DO2 returned transiently to control values. However, recovery of DO2 was short-lived in all hemoglobin solution groups, and, by 4 hrs postresuscitation in all groups, DO2 was less than the DO2 of the dogs receiving whole blood (p < .05). These changes were associated with decreases in total hemoglobin concentrations compared with the values immediately before resuscitation (p < .05). In addition, with resuscitation using the PHP solutions, blood smears demonstrated aggregation of red blood cells and platelets. On day 8 after hemorrhagic shock, the survival rate was 100% for whole blood and PHP44, 86% for 8% stroma-free hemoglobin, and 33% for PHP88. CONCLUSIONS: Resuscitation from severe hemorrhagic shock with 8% stroma-free hemoglobin, PHP44, or PHP88 is equally effective in restoring cardiac index and vascular pressures as using whole blood. However, resuscitation with the three hemoglobin solutions only transiently restored DO2 after hemorrhagic shock. The subsequent reduction of DO2 compared with the DO2 value using whole blood was due mostly to hemodilution. With the two PHP solutions, formation of red blood cell aggregates probably resulted in sequestration of red cell mass and additional loss of oxygen carrying capacity.

Animals↗

Fat emulsion particle-size distribution in total nutrient admixtures.

The fat particle-size distribution in and physical stability of two commercially available lipid emulsions before and after their use in total nutrient admixtures (TNAs) are reported. Four TNAs without electrolytes and four TNAs with electrolytes were prepared; each type of TNA was prepared with Liposyn II and with Intralipid. Particle size was measured in the < 1-micron range by using photon correlation spectroscopy and in the 2-60-microns range by using light blockage. Admixtures with or without electrolytes were stored for two or nine days at 4 degrees C followed by one day at 25 degrees C. For the fraction of fat particles of < 1 micron in diameter, Intralipid and Liposyn II had a mean particle size of 374 and 313 nm, respectively. The admixtures containing electrolytes showed a decrease in mean particle size of about 7%. Admixtures with Intralipid contained 2 x 10(7) particles larger than 2 microns per milliliter (1.7% of total fat), compared with 1 x 10(6) particles per milliliter (0.05-0.15% of total fat) for admixtures with Liposyn II. The addition of electrolytes increased the particle counts for Liposyn II-containing admixtures. Upon storage, Intralipid-containing admixtures with electrolytes showed an initial increase followed by a decrease in the mean diameter of particles of < 1 micron. All the admixtures were stable in terms of pH and visual appearance. Intralipid-containing admixtures with electrolytes showed a decrease in the number of particles in the 2-60-microns size range, while Liposyn II-containing admixtures with electrolytes showed an increase.(ABSTRACT TRUNCATED AT 250 WORDS)

Drug Incompatibility↗