Search PubMed⌕ Search

Biomedical subjects

M Salem

Publications and source records attributed to M Salem.

At least 37 records · Page 2Linked to original sources

Progressive magnesium deficiency increases mortality from endotoxin challenge: protective effects of acute magnesium replacement therapy.

OBJECTIVES: To study the effects of endotoxin on magnesium homeostasis; to determine if progressive magnesium deficiency alters outcome from endotoxin challenge; and to evaluate the efficacy of magnesium therapy in reducing endotoxin-induced mortality. DESIGN: Prospective, placebo-controlled, randomized, multiexperiment studies. SETTING: Research laboratory of a university hospital. SUBJECTS: Male Sprague Dawley rats (n = 299). INTERVENTIONS: Experiment 1 was designed to test if endotoxin alters magnesium homeostasis. Circulating total and ionized magnesium (estimated by ultrafilterable values) concentrations were determined in blood samples collected from animals after the randomized administration of placebo or 0.3, 3.0, or 30 mg/kg of endotoxin. A baseline blood sample was collected and then a second blood sample was obtained at 5, 15, 30, 60, 120, or 180 mins after endotoxin or placebo administration. In experiment 2, animals were randomized to receive magnesium-sufficient diets or magnesium-deficient diets for 6 wks. After 6 wks, the effects of the randomized administration of 3.0 mg/kg endotoxin or placebo were evaluated on mortality and analyte values (pH and blood gases, sodium, potassium, chloride, glucose, ionized calcium, hematocrit, total and ultrafilterable magnesium concentrations) in the three study groups (magnesium-sufficient, 3-wk magnesium-deficient, or 6-wk magnesium-deficient). In experiment 3, magnesium-deficient animals were randomized to receive 50 mmol/kg magnesium chloride or placebo, before or after the administration of 3.0 mg/kg of endotoxin. Baseline and 24-hr analyte determinations were performed and outcome was analyzed. MEASUREMENTS AND MAIN RESULTS: Experiment 1: Significant increases (p < .05) in circulating total magnesium concentrations were found in animals that received 30 mg/kg of endotoxin, at 120 mins (0.79 +/- 0.10 vs. 0.60 +/- 0.05 mmol/L), and 180 mins (0.74 +/- 0.04 vs. 0.56 +/- 0.04 mmol/L) compared with baseline values. Similarly, significant increases (p < .05) in ionized magnesium concentrations were observed 120 and 180 mins after 3.0 and 30 mg/kg of endotoxin compared with baseline values. Experiment 2: Magnesium deficiency was strongly (p < .02) associated with increased mortality from endotoxin challenge. Endotoxin administration (3.0 mg/kg) was lethal in 10 (43%) of 23 magnesium-sufficient animals, 15 (65%) of 23 3-wk magnesium-deficient animals, and 20 (83%) of 24 6-wk magnesium-deficient animals. Experiment 3: In magnesium-deficient animals, rats treated with magnesium replacement therapy had significantly increased survival from endotoxin administration (15 [52%] of 29 vs. five [17%] of 29, p < .01) compared with placebo-treated animals. CONCLUSIONS: a) Endotoxin challenge causes significant increases in circulating total and ionized magnesium concentrations. b) Progressive magnesium deficiency is strongly associated with increased lethality, and magnesium replacement therapy provides significant protection from endotoxin challenge. c) These experimental results support the concept that cellular injury is probably associated with increases in circulating magnesium concentrations. Furthermore, these experimental findings suggest that magnesium deficiency predisposes to worse outcome from endotoxin challenge, and that replacement therapy in the setting of magnesium deficiency may be warranted, especially in critically ill subjects.

Animals↗

Treatment of renal colic by desmopressin intranasal spray and diclofenac sodium.

The vasopressin analogue, 1-desamino-8-arginine vasopressin (desmopressin), is a potent antidiuretic without the pressor effects of vasopressin. A total of 18 patients with acute renal colic due to stone disease received 40 microgramsf1p4mopressin intranasal spray with encouraging results. There was a significant decrease in the colic pain intensity from an initial mean visual analogue score of 67 +/- 17 mm. to 39 +/- 36 mm. within 30 minutes (p < 0.001). Eight patients (44.4%) had complete pain relief within 30 minutes of administering intranasal desmopressin spray. Nine of 10 patients who required intramuscular diclofenac sodium achieved complete pain relief within another 30 minutes. In other words, when intranasal desmopressin spray was administered before diclofenac sodium, 94.4% of the patients achieved complete pain relief and were discharged home. The mechanism of analgesic action of desmopressin in renal colic is uncertain. At the peripheral level, desmopressin may alleviate the acute renal colic through its potent antidiuretic effect or by relaxing the renal pelvic and ureteral smooth muscles. The central analgesic effect of desmopressin by stimulating the release of the hypothalamic beta-endorphin is proposed. We conclude that intranasal desmopressin spray can be used successfully in the treatment of renal colic. It may also replace prostaglandin synthetase inhibitors in treating renal colic with the advantage of avoiding the potential side effects. Further studies are needed to investigate whether the combination of desmopressin with analgesics or spasmolytic drugs offers competitive results compared with those achieved by prostaglandin synthetase inhibitors in the treatment of renal colic.

Acute Disease↗

Perioperative glucocorticoid coverage. A reassessment 42 years after emergence of a problem.

OBJECTIVE: The authors review the historical basis for the provision of perioperative glucocorticoid coverage, and detail the evolution in the understanding of the role of the hypothalamic-pituitary-adrenal cortical (HPA) axis in response to physical stressors. New recommendations are proposed for glucocorticoid-dependent patients who require anesthesia and surgery. SUMMARY BACKGROUND DATA: In 1952, a patient developed surgery-associated adrenal insufficiency as a result of preoperative withdrawal from glucocorticoid therapy. That case report, and one other in the ensuing 12 months, prompted the publication of recommendations for perioperative glucocorticoid coverage, which became the standard of care. The understanding of the role of the HPA axis in the stress response has been subsequently refined; however, recommendations for perioperative glucocorticoid coverage have not been altered in parallel. METHODS: Studies were identified beginning with the first reports of the physiologic actions of the adrenal glands (1855) and the description and clinical use of cortisone (1930-1993). Studies were selected for review if they were related to or evaluated the provision of stress-related glucocorticoid administration. All clinical studies were evaluated to determine the basis for the provision of perioperative glucocorticoid coverage and the validity of the data used to justify these conclusions. CONCLUSIONS: Clinical and experimental evidence support the concept that the current amount of perioperative glucocorticoid coverage is excessive and has been based on anecdotal information. New recommendations are proposed which suggest that the amount and duration of glucocorticoid coverage should be determined by: a) the preoperative dose of glucocorticoid taken by the patient, b) the preoperative duration of glucocorticoid administration, and c) the nature and anticipated duration of surgery.

Glucocorticoids↗

Ultrafilterable hypomagnesemia in neonates admitted to the neonatal intensive care unit.

OBJECTIVE: To evaluate the frequency and clinical correlates of ultrafilterable hypomagnesemia in neonates admitted to the neonatal intensive care unit (ICU). DESIGN: Prospective, observational study. SETTING: Massachusetts General Hospital and Mount Auburn Hospital. PATIENTS: A total of 117 patients (84 neonatal ICU patients and 33 normal newborns) studied over a 2-yr period of time. MEASUREMENTS: Blood samples were collected during the first 48 hrs after admission. The concentrations of magnesium (total and ultrafilterable), ionized calcium, parathyroid hormone, electrolytes, glucose and arterial blood gases were determined. RESULTS: Ultrafilterable circulating magnesium concentrations were determined in 74 of 84 neonatal ICU patients. On admission to the neonatal ICU, 23 (31.1%) of 74 neonates had ultrafilterable hypomagnesemia; two (2.7%) of 74 patients had ultrafilterable hypermagnesemia. Neonatal ICU patients had significantly lower (p < .001) ultrafilterable magnesium concentrations compared with normal neonates. Hypomagnesemic ICU patients required mechanical ventilatory support more frequently than did normomagnesemic ICU neonates (p < .05). Ionized hypocalcemia was a common finding in our patients (34 [42%] of 81). However, ultrafilterable hypomagnesemia was not statistically associated with ionized hypocalcemia (p > .05). Despite the below normal serum concentrations of ultrafilterable magnesium observed in our study, there was no impairment in parathyroid hormone secretion. CONCLUSIONS: Ultrafilterable hypomagnesemia is a common finding in neonates admitted to the ICU. Ultrafilterable hypomagnesemia is associated with the need for mechanical ventilation. To our knowledge, this is the first report of ultrafilterable magnesium concentrations in normal and sick neonates.

Bias↗

Adverse effects of dialyzers manifesting during the dialysis session.

The intradialytic symptoms that can be linked to components of the extracorporeal circuit of greatest clinical importance are the Type A (anaphylactoid) reactions. Most of these are IgE-mediated reactions due to ethylene oxide and are preventable by adequate degassing of the dialyzer by the manufacturer and by adequate rinsing of the dialyzer just prior to use. AN69-associated reactions are a second group, and are probably mediated by membrane-induced bradykinin generation coupled with ACE-inhibitor induced prolongation of bradykinin half-life. Type A reactions occur in a reuse setting, alos, and these may be related to some as yet poorly understood interaction between bleach, reuse sterilants, and certain dialyzer membranes, again, with ACE inhibitors playing an amplifier role. There is no compelling evidence linking membrane-induced complement activation to type A dialyzer reactions. However, there is a large body of evidence in animal models that exposure to complement fragment-releasing membranes can increase the pulmonary artery pressure and increase thromboxane formation. Thus, at least in principle, a case can be made for using unsubstituted cellulose membranes with caution in patients with a history of atopy or eosinophilia, particularly if acetate dialysate is to be used. Such a caution, however, must be viewed as conjectural in the absence of definitive evidence. Type B dialyzer reactions (mild back and chest pain 20-60 min into the dialysis session) is a phenomenon that is in the process of vanishing. The reason why is unclear. These reactions may have been due to some sort of dialyzer contaminant, or they may have been due to complement fragment release and required the use of acetate dialysate as a cofactor. In any event, recent well designed studies fail to find any differences in symptoms between unsubstituted cellulose and synthetic membranes. Membrane-induced complement fragment release also may play a minor role in dialysis hypoxemia, but evidence is conflicting in this area. Again, the use of acetate dialysate appears to be an important cofactor. Post-dialysis events which may be conceivably linked to the delayed effects of complement fragment releasing membranes need to be evaluated in controlled studies. Studies suggesting increased post-dialysis catabolism with use of unsubstituted cellulose membranes need to be confirmed in dialysis patients, and symptomatic correlates should be sought and evaluated.

Anaphylaxis↗

Hormonal responses to surgical stress in children.

The hormonal responses to surgical stress in adults are well characterized. We hypothesized that children have age-related differences in the "stress responses" to surgery. To test this hypothesis we prospectively studied 98 children (aged 2 to 20 years) undergoing elective surgical procedures under general anesthesia. Preoperative and postoperative (1 hour postoperation) blood samples were obtained and serum prolactin and cortisol concentrations were measured. Patient data were stratified by patient age and length of operation. All patients had significant (P < .05) increases in serum cortisol and prolactin concentrations 1 hour postoperatively as compared with preoperative values. However, there were no significant differences in prolactin and cortisol responses to surgery based on the age, anesthetic technique, or length of operation. Females had higher mean (+/- SD) serum prolactin concentrations (78.41 +/- 62.23 micrograms/L) as compared with males postoperatively (39.8 +/- 21.75 micrograms/L) (P < .05). We conclude the following: (1) children have significant increases in circulating prolactin and cortisol concentrations following surgery and anesthesia, and that those increases are not affected by age, length of surgery, or anesthetic technique; and (2) females have greater prolactin responses to surgery and anesthesia than males.

Adolescent↗

Magnesium administration and dysrhythmias after cardiac surgery. A placebo-controlled, double-blind, randomized trial.

OBJECTIVE: To determine whether magnesium administration is effective in reducing postoperative morbidity and mortality after cardiac surgery. DESIGN: Randomized, double-blind, placebo-controlled trial. SETTING: A tertiary acute-care 500-bed university teaching hospital. PATIENTS: Over a 6-month period, 100 patients electively scheduled for cardiac surgery involving cardiopulmonary bypass were studied. INTERVENTIONS: Fifty patients were randomized to receive an intravenous infusion of magnesium chloride, 2 g, and 50 patients received placebo intraoperatively after the termination of cardiopulmonary bypass. RESULTS: Magnesium-treated patients had a significantly decreased frequency (P < .04) of postoperative ventricular dysrhythmias (eight [16%] of 50) compared with placebo-treated patients (17 [34%] of 50). Patients who were normomagnesemic postoperatively had new supraventricular dysrhythmias less frequently (P < .03) than patients who were hypomagnesemic postoperatively (eight [17%] of 48 vs 19 [37%] of 52). Compared with placebo-treated patients, magnesium-treated patients had significantly higher (P < .02) postoperative cardiac indices in the intensive care unit (2.8 +/- 0.1 vs 2.5 +/- 0.1 L/min per m2). Patients with postoperative total and ultrafilterable hypomagnesemia had postoperative ventricular dysrhythmias (P < .04) and required prolonged mechanical ventilatory support (P < .01) more frequently than patients without postoperative hypomagnesemia. CONCLUSIONS: Total and ultrafilterable hypomagnesemia are prevalent findings in cardiac surgery patients, and postoperative hypomagnesemia is strongly associated with clinically important morbidity. Magnesium administration decreased the frequency of postoperative ventricular dysrhythmias and increased the stroke volume and thereby cardiac index in the early postoperative period.

Adult↗

Bedside diagnostic blood testing. Its accuracy, rapidity, and utility in blood conservation.

OBJECTIVE: --Bedside diagnostic testing utilizing microchemistry instruments potentially offers physicians the opportunity to evaluate urgent blood test results rapidly and reliably using only drops (250 microL) of whole blood. The use of microchemistry technology may also represent an essential component of a blood conservation program in acutely ill patients. We tested the hypothesis that a microchemistry instrument would have important advantages in the intensive care unit, including rapid turnaround time, decreased iatrogenic blood loss, and the provision of accurate analyte results. DESIGN: --One-year prospective, random-sample comparative study. SETTING: --A tertiary, acute care, 1000-bed university teaching hospital and a 450-bed university-affiliated community hospital. PATIENTS: --Blood samples from 850 patients were analyzed. RESULTS: --There were strong correlations (for pH, R2 = .97; PCO2, R2 = .97; PO2, R2 = .99; sodium, R2 = .83; potassium, R2 = .94; chloride, R2 = .90; glucose, R2 = .98; and hematocrit, R2 = .92) when paired samples were analyzed simultaneously in the laboratory comparing the microchemistry instrument and currently accepted clinical laboratory instruments. There were significant correlations (for pH, R2 = .91; PCO2, R2 = .94; PO2, R2 = .97; sodium, R2 = .91; potassium, R2 = .86; chloride, R2 = .91; ionized calcium, R2 = .82; glucose, R2 = .96; and hematocrit, R2 = .75) but increased variability occurred in some analyte results when samples were first analyzed in the intensive care unit (using the microchemistry instrument) and then transported to the laboratory in the routine fashion for "stat" determinations. CONCLUSIONS: --The multichannel microchemistry instrument provided accurate analyte determinations when compared with accepted clinical laboratory instruments. Significant savings of time and blood were also realized by the use of a microchemistry instrument in the intensive care unit. Bedside microchemistry may provide clinically important advantages in emergency departments, operating rooms, and neonatal, pediatric, coronary, adult medical and surgical, trauma, and burn intensive care units.

Blood Chemical Analysis↗

Hypomagnesemia is a frequent finding in the emergency department in patients with chest pain.

STUDY OBJECTIVE: To evaluate the frequency of low blood levels of total and ultrafilterable magnesium (total and ultrafilterable hypomagnesemia) in patients with chest pain in the emergency department, and to determine if hypomagnesemia is associated with other clinically important diagnostic and outcome variables in cardiac care. SETTING: An emergency department of a university teaching hospital. DESIGN: Prospective study of extracellular magnesium homeostasis in patients with chest pain in the emergency department and a cohort of patients without chest pain with a clinical indication for blood sampling. PATIENTS: During a 4-month period, 147 patients presenting to the emergency department were studied: 67 patients (mean +/- SD age, 61.4 +/- 13 years) with a chief complaint of chest pain (study group) and 80 patients (55.6 +/- 19 years) with other diagnoses (control group). RESULTS: Total and ultrafilterable hypomagnesemia occurred more frequently in patients with chest pain (20/67 [30%] and 9/67 [13%]) than in the control group (12/80 [15%] and 3/80 [4%]). Patients with a chief complaint of chest pain who were receiving diuretic medications were hypomagnesemic more frequently (9/16 [56%]) than patients not receiving diuretics (12/51 [23%]). In patients with chest pain admitted to the hospital with a diagnosis of "rule out" myocardial infarction, the frequency of hypokalemia was greater among hypomagnesemic patients (6/14 [43%]) than normomagnesemic patients (3/31 [10%]). A similar frequency of hypomagnesemia was noted in patients with a final diagnosis of myocardial infarction (4/15 [27%]) when compared with other patients admitted with chest pain (10/31 [32%]) in whom myocardial infarction was excluded. No association was noted among hypomagnesemia and length of hospital stay or the occurrence of hypotension or dysrhythmias. CONCLUSIONS: Total and ultrafilterable hypomagnesemia are frequent occurrences in patients with and without chest pain in the emergency department. Diuretic use is associated with hypomagnesemia in patients presenting with chest pain in the emergency department. These results support the concept that hypomagnesemia is common in patients with chest pain in the emergency department and is associated with hypokalemia but is not predictive of whether the patient with chest pain has had an acute myocardial infarction.

Chest Pain↗