Use of Tris-hydroxymethyl aminomethane in severe lactic acidosis due to highly active antiretroviral therapy: a case report.

BACKGROUND: Lactic acidosis is a rare, yet life-threatening adverse drug effect of highly active antiretroviral therapy (HAART), specifically stavudine and lamivudine. These nucleoside analogue reverse transcriptase inhibitors (NRTIs) are commonly used to treat patients infected with the human immunodeficiency virus (HIV). CASE: We report the use of Tris-hydroxymethyl aminomethane (THAM) to treat severe lactic acidosis due to HAART in a 50-year-old African-American woman. NRTIs can cause hyperlactinaemia by interfering with mitochondrial oxidative phosphorylation function, which normally removes H(+) generated by the hydrolysis of adenosine triphosphate. This side-effect is associated with a high mortality in patients infected with HIV. One explanation for this high mortality is that lactic acidosis is typically refractory to treatment with commonly used buffering agents. CONCLUSION: THAM generates serum bicarbonate, and reduces the level of carbon dioxide in arterial blood. Both of these qualities appear to make THAM an ideal agent for treating lactic acidosis caused by HAART.

Growth hormone and pulmonary disease. Metabolic effects in patients receiving parenteral nutrition.

Six severely malnourished patients with chronic obstructive pulmonary disease were maintained for 3 days with infusions of 5% dextrose in water followed by 12 days of eucaloric total parenteral nutrition. On days 8 through 11, they received 30 micrograms/d of growth hormone and twice this amount on days 11 through 15. Growth hormone had no significant effects on the plasma concentration of glucose, cortisol, or glucagon but caused a 50% increase in insulin and a 250% increase in somatomedin C concentrations. A positive nitrogen balance of 2 g/d due to growth hormone was probably mediated by insulin. Growth hormone-induced increases in energy expenditure and fat oxidation and decrease in glucose oxidation cannot be accounted for by insulin. The ability of growth hormone to improve nitrogen balance may be particularly important for malnourished patients with chronic obstructive pulmonary disease who, because of their pulmonary insufficiency, are intolerant of excess nutrients.

Modulation of lipopolysaccharide-induced tumor necrosis factor-alpha and nitric oxide production by dopamine receptor agonists and antagonists in mice.

The effects of various agonist and antagonists of dopamine D1 and D2 receptors on lipopolysaccharide (LPS)-induced tumor necrosis factor-alpha (TNF-alpha) and nitric oxide (NO) production was investigated in mice. Pretreatment of animals with bromocryptine or quinpirole, agonists of dopamine D2 receptors caused a blunting of both the TNF-alpha and NO responses to LPS injected intraperitoneally. Sulpiride, an antagonist of dopamine D2 receptors, decreased the LPS-induced TNF-alpha plasma levels in a dose-dependent manner and inhibited the LPS-induced NO production by peritoneal macrophages. Bromocryptine or quinpirole blunted both the TNF-alpha and NO response to LPS. SCH-23390, an antagonist of dopamine D1 receptors did not alter LPS-induced TNF-alpha production, but inhibited LPS-induced NO production. These results indicate that while the D2 subtype of dopamine receptors is involve in the modulation of both LPS-induced TNF-alpha and NO production, dopamine D1 receptors only regulate the production of NO. Since several drugs possess effect on dopamine D2 receptors, the present observations may be of clinical relevance.

Differential effect of selective block of alpha 2-adrenoreceptors on plasma levels of tumour necrosis factor-alpha, interleukin-6 and corticosterone induced by bacterial lipopolysaccharide in mice.

The effect of selective block of alpha 2-adrenoreceptors on plasma levels of tumour necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6) and corticosterone induced by bacterial lipopolysaccharide (LPS) was investigated in mice using ELISA and RIA. It was found that the LPS-induced TNF-alpha response was significantly blunted in mice pretreated with CH-38083, a novel and highly selective alpha 2-adrenoreceptor antagonist (the alpha 2/alpha 1 ratio is > 2000). In contrast, LPS-induced increases in both corticosterone and IL-6 plasma levels were further increased by CH-38083. Since it has recently been shown that the selective block of alpha 2-adrenoreceptors located on noradrenergic axon terminals resulted in an increase in the release of noradrenaline (NA), both in the central and peripheral nervous systems, and, in our experiments, that propranolol prevented the effect of alpha 2-adrenoreceptor blockade on TNF-alpha plasma levels induced by LPS, it seems likely that the excessive stimulation by NA of beta-adrenoreceptors located on cytokine-secreting immune cells is responsible for this action. Since it is generally accepted that increased production of TNF-alpha is involved in the pathogenesis of inflammation and endotoxin shock on the one hand, and corticosterone and even IL-6 are known to possess anti-inflammatory properties on the other hand, it is suggested that the selective block of alpha 2-adrenoreceptors might be beneficial in the treatment of inflammation and/or endotoxin shock.

Submaximal exercise in emphysema and malnutrition at two levels of carbohydrate and fat intake.

Eight malnourished patients with emphysema (EMPH) and eight malnourished patients without evidence of lung disease (MLAN) received an infusion of 5% dextrose plus electrolytes (D5W) for 48 h and were then randomly assigned to a hypercaloric diet with either 53% of the calories as carbohydrate (CB) or with 55% as fat (FB) for the 1st wk, maintaining a constant protein intake. The alternate diet was given the following week. Ventilation and gas exchange were measured during supine cycle ergometry at 0, 12, and 25 W during the D5W, CB, and FB diet periods. At each exercise intensity, the EMPH group demonstrated a 12-15% greater O2 consumption, a lower respiratory quotient, and an O2 debt larger than that of the MALN group. Resting ventilation was higher during the CB than FB regimen in both groups of patients, but during the CB diet the EMPH group had a more exaggerated ventilatory response than the MALN group. The results demonstrate that EMPH patients have an unusual metabolic pattern during hypercaloric feeding and exercise. Furthermore in EMPH patients a FB regimen does not appear to create the additional stress on the respiratory system during exercise that is generated with a CB regimen.

Nutrition, the gastrointestinal tract and the acquired immune deficiency syndrome. Facts and perspectives.

Diarrhoea and malnutrition are common findings in patients with the Acquired Immune Deficiency Syndrome (AIDS). In this disease, enteropathy leads to fat and D-xylose malabsorption and chronic non-specific inflammation of the small bowel. Moreover, gastrointestinal infection can induce severe diarrhoea. Depletion in real body cell mass, body fat content, and weight loss have been observed. Nutritional therapy is mandatory when weight loss is 10% or greater. Enteral feeding is not easily achieved. Parenteral feeding including fat as a nonprotein calorie source improves general condition. The use of intravenous fat emulsions has been hypothesized to have several beneficial effects. Fluidisation of human immunodeficiency virus membranes by lipid emulsions through cholesterol extraction could decrease the infectivity of the virus. Long term intravenous nutrition may be more than a treatment for malabsorption and depletion; it may possibly have direct pharmacological effects.

The use of inferior vena cava filter as a treatment modality for massive pulmonary embolism. A case series and review of pathophysiology.

The use of inferior vena cava (IVC) filter for massive pulmonary emboli (PE) with cardiopulmonary instability has not been clinically studied. We present a case series of six such patients who received an IVC filter with anticoagulation rather than thrombolysis because of high risk of bleeding. Acute pulmonary embolectomy was considered, but was not possible for a variety of individual clinical situations. These six hospitalized patients prospectively followed during their admission. They were triaged to three medical intensive care units (ICUs) and one surgical ICU in three university teaching hospitals. One patient was transferred from another institution. All six patients had severe hypoxia and tenuous cardiopulmonary status. All required high inspiratory oxygen and hemodynamic support; two required mechanical ventilation and vasopressors. An IVC filter was placed emergently and anticoagulation was started immediately All six patients had resolution of pulmonary thromboemboli (PTE) on anticoagulation while the IVC filter prevented further PE. All six patients were discharged home in their pre-critical illness state. None ofthe patients suffered complications from this therapy and had excellent resolution ofcardiopulmonary collapse. The IVC filter placement prevented further major embolic events while the PTE resolved with anticoagulation. An IVC filter should be considered as an adjunct to anticoagulation therapy for those patients with massive PE and cardiopulmonary instability who are not candidates for thrombolysis, and acute pulmonary embolectomy is not readily available or is of very high risk.

Parenteral use of medium-chain triglycerides: a reappraisal.

Over the last two decades, the clinical use of intravenous fat emulsions for the nutritional support of hospitalized patients has become routine. During this time long-chain triglycerides (LCT) derived from soybean and/or safflower oils were the exclusive lipid source for these emulsions, providing both a safe calorically dense alternative to dextrose and essential fatty acids needed for biologic membranes and the maintenance of immune function. During the past decade, the availability of novel experimental triglycerides for parenteral use has generated interest in the use of these substrates for nutritional and metabolic support. Medium-chain triglycerides (MCT), long advocated as a superior substrate for parenteral use, possess many unique physiochemical and metabolic properties that make them theoretically advantageous over their LCT counterparts. Although not yet approved in the United States, preparations containing MCT have been widely available in Europe. Intravenous MCT preparations, either as physical mixtures or structured lipids, have been used clinically in patients with immunosuppresion, critical illness, liver and pulmonary disease and in premature infants. Despite great promise, the clinical data comparing the efficacy of MCT-based lipid emulsions to their LCT counterparts has been equivocal. This may be due in part to the limited nature of the published clinical trials. Measures of efficacy for parenteral or enteral nutritional products has taken on new meaning, in light of the reported experience using immunomodulatory nutrients. Current concerns about cost of medical care and resource use warrant careful deliberation about the utility of any new and expensive therapy. Until clinical data can fulfill expectations derived from animal studies, it is difficult to advocate the general use of MCT-based lipid emulsions. Future clinical studies with MCT-based emulsions should have clear outcome objectives sufficient to prove their theorized metabolic superiority.

Parenteral nutrition and oral intake: effect of branched-chain amino acids.

The effect of peripheral parenteral nutrition (PPN) on voluntary food intake was examined in healthy male subjects. Each study (lasting 17 to 19 days) was divided into three phases: Ringer's lactate (RL); PPN administered as a combination of glucose, fat, and amino acids; and finally RL. During the middle phase, some of the subjects received a parenteral formula in which half of the amino acids had been replaced with the branched-chain amino acids (BCPPN). When PPN was infused, subjects reduced their food intake within 48 hours by approximately 80% of the infused calories (p less than 0.001) within 48 hours, whereas intake was reduced by less than 40% of the infused calories when BCPPN was infused. Use of branched-chain amino acid-enriched parenteral nutrition may minimize the reduction in food intake seen during intravenous nutrition, possibly hastening a return to normal eating.

Parenteral nutrition and oral intake: effect of glucose and fat infusions.

The effect of intravenous nutrition on voluntary oral intake was studied in healthy male volunteers. Subjects were confined to the Surgical Metabolic Unit for the 17 to 19 day study and were restricted to commercial liquid diet. Each study consisted of three consecutive phases: (1) Ringer's lactate (RL), (2) peripheral parenteral nutrition (PPN) administered for 5 or 6 days as a combination of glucose (caloric load equal to 34% resting energy expenditure, REE), fat (34% REE), and amino acids (17% REE) or a single nutrient infusion of glucose (68% REE), fat (68% REE), glucose (34% REE), or fat (34% REE), and (3) RL for the third period. When all three nutrients or glucose alone (68% REE) were given, subjects decreased daily voluntary food intake within 24 to 48 hr by an amount that closely compensated for the infused calories. Intake was reduced by only 20% to 40% of the infused calories when fat alone (68% REE) was given. There were no significant effects when the lower levels of glucose and fat were given. These data suggest the presence of a postabsorptive control of food intake in humans that is sensitive to the circulating supply of fuels.

Risks and benefits of home parenteral nutrition in the acquired immunodeficiency syndrome.

The gastrointestinal tract is a major target of the human immunodeficiency virus. Many AIDS patients have weight loss and/or diarrhea. Parenteral nutrition can be used to treat malnutrition associated with malabsorption. We reviewed retrospectively the clinical course of 22 patients with AIDS and weight loss greater than 10% who received home parenteral nutrition (HPN) for 56.2 patient-months. Mean weight loss was 21.4%, mean duration of HPN 2.55 months, mean age 37.4 years. Fifteen patients gained weight, six stabilized and two continued to lose weight. Nine patients returned to previous activity. Five died. The rates of catheter-related sepsis, complications, and metabolic disturbances were 0.12, 0.25, and 0.12/100 catheter days, respectively, results identical to those reported in other patient populations where HPN is commonly applied. We found that HPN induced weight gain and clinical improvement in most patients without higher risks of sepsis than in patients with malignancies.

Glycerol metabolism in humans: validation of 2H- and 13C-labelled tracers.

For a tracer to be valid it must follow the metabolism of the tracee without distortion. Especially when the tracer contains several deuterium substitutions, the tracer can be altered or degraded differently from the metabolite it is to trace or be subject to distorting isotope effects. To determine whether 2H5-glycerol is a valid tracer for following glycerol kinetics, 2H5-glycerol and [2-13C]glycerol tracers were infused simultaneously in six healthy postabsorptive adult subjects. After 90 min of tracer infusion, epinephrine was also infused for 60 min to stimulate lipolysis and increase glycerol flux. Glycerol flux increased from 2.2 +/- 0.3 to 6.7 +/- 0.4 mumol/kg per minute (with the 13C tracer) and from 2.2 +/- 0.3 to 6.7 +/- 0.3 mumol/kg per minute (with the 2H tracer) when epinephrine was infused. There was no significant difference in glycerol flux measured with the 2H tracer compared to the 13C tracer either under basal or a stimulated flux condition. These results indicate that 2H5-glycerol is a valid tracer for measuring glycerol metabolism in humans.

Field management and critical care in mass disasters.

As previously discussed, the majority of injury cases do not necessarily involve dramatic life-saving actions, but rather very rudimentary, promptly applied precautions. For most victims of trauma, therefore, we offer reassurance and simple compassion in their time of need. One of the more important lessons to be learned here is that, beyond prehospital injury "management" or "treatment," we should always remember to provide the best possible prehospital injury care. By responding as soon as possible and by delivering reassurance and compassion to those who are injured and frightened, we are providing one of the most sacred aspects of the Hippocratic mission. Despite wonderful technologic advances and the need for aggressiveness in disaster management, these humanistic values must always be maintained by those to whom care is entrusted. Successful transport of disaster victims, whether in the prehospital phase or during interhospital transfer, requires careful attention to treatment priorities, such as simple measures for airway control and ventilation, and care to prevent further injuries by appropriate immobilization techniques. The use of fully equipped teams of multidisciplinary critical care specialists in mass disaster situations is in its infancy. It is clear that with properly adapted hardware and personnel trained to function in adverse environments while effectively delivering intensive care to a large number of patients with a variety of clinical syndromes, survival can be significantly increased for the most acutely ill.

Organization and management of critical care systems in unconventional situations.

Critical care medicine is a field of medicine using the highest concentration of expensive diagnostic and life-support technology for the benefit of a single individual. Conventional use of this resource and specialty is clearly understood, despite the fact that it is not necessarily comparable among different institutions. Some of the major issues in using critical care as a medical tool during extraordinary stress on the hospital, and the potential for using it in unconventional environments outside an established institution, have been reviewed. It is clear that the expertise and multidisciplinary approach can be of great use in disaster response, and a national effort toward integrating critical care into overall medical response is in progress.

Nutritional and metabolic support.

The problem of hunger accompanies any mass casualty situation that results in large numbers of patients with traumatic and burn injuries complicated by sepsis and end organ failure. This is caused by the inability of many of these patients to eat. Such patients require artificial nutrition. A rescue operation that does not provide adequate artificial nutrition, no matter how well organized with respect to field stabilization, surgical intervention, and intensive care, will find many of its patients dying of multiorgan disorders due to nutritional failure. This article is concerned with how to provide such artificial nutrition.

Clinical algorithm for initial fluid resuscitation in disasters.

This article reviews past experience with branch-chain decision trees for fluid resuscitation of various emergency conditions and analyzes the effects of compliance with the algorithm on mortality and shock-related complications. On the basis of this analysis, the authors propose a new algorithm for fluid resuscitation of mass casualties when only palpable systolic blood pressure is available and when blood pressure, hematocrit, central venous pressure, urine output, and arterial blood gases are available.

Consensus conferences in critical care medicine. Methodologies and impact.

Consensus conferences for the purposes of producing practice guidelines are occurring with increasing frequency both nationally and internationally. The international collaboration of national sciences in these efforts could have a dramatic impact on international standards of care. Too little emphasis is given to conference evaluations in terms of validity of methods, quality of recommendations, and influence on clinical practice and patient outcome. This article provides an overview of consensus methods used to produce guidelines in critical care. It also discusses the strengths and weaknesses of these methods, and how these may influence consensus guidelines. Finally, a brief overview of theoretically sound methods that can serve as benchmarks to evaluate current methods, and the bases for the development of improved methods is provided.

Endovascular stented graft repair of a pseudoaneurysm of the subclavian artery caused by percutaneous internal jugular vein cannulation: case report.

In high-risk patients endovascular repair of a pseudoaneurysm with a stented graft is a safe and reasonable treatment option that can preclude significant morbidity and shorten hospital stay. We report a case of pseudoaneurysm of the subclavian artery after internal jugular vein cannulation that was treated successfully with an endovascularly inserted, stented graft. The case report highlights the importance of recognizing this unusual but serious complication of percutaneous internal jugular vein catheterization through careful clinical examination, prompt duplex scanning, and arteriography.

Reassessing intensive care for patients with the acquired immunodeficiency syndrome.

The number of patients with the acquired immunodeficiency syndrome (AIDS) admitted to hospitals is increasing dramatically. Treatments such as zidovudine, aerosolized pentamidine, and nutritional support are being administered to subacutely ill patients with increasing effectiveness. The number of patients with AIDS treated in intensive care units, on the other hand, has been decreasing progressively, perhaps as a result of a mortality rate close to 90%. However, because recent data demonstrate (1) a lower mortality rate in patients with AIDS who receive mechanical ventilation and (2) the ability to reverse the wasting syndrome in selected groups, we propose a reassessment of the criteria for intensive care unit admission of patients with AIDS.

Oxygen transport and utilization.

The evaluation and management of oxygen delivery (Do2) and consumption (Vo2) of patients with acute medical and surgical illnesses have been subject to controversy and reevaluation. It has been established that a relationship between oxygen delivery and oxygen consumption exists, and is very complex, particularly in diseases in which various factors individually or collectively affect it. The care of critically ill patients routinely involves the manipulation of the Vo2-Do2 relationship, and extensive research, both experimental and clinical, has been done to improve our understanding of this relationship in health and disease with the hope for improved outcomes. Regional measures of oxygenation are a relatively new area of interest with a limited amount known about the regional relationship between Do2 and Vo2. The adequacy of regional oxygenation appears to play an important role in organ dysfunction in critical illness. Standard measures of assessing systemic oxygenation are often insensitive in detecting tissue hypoxia, which can often vary among and within various organs. New noninvasive technologies to measure the adequacy of regional measures of oxygenation are being developed, with gastrointestinal tonometry getting much clinical attention. The exact role of these technologies in the management of critically ill patients, and whether they will improve survival, has not yet been determined. It is likely that the ability to care successfully for critically ill patients will come from a better understanding of not only global, but also regional, cellular, and subcellular metabolism.