The use and interpretation of indirect calorimetry in critically ill patients.
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Adolescent↗
Biomedical subjects
J Blumer
Publications and source records attributed to J Blumer.
Catecholamine release, growth hormone secretion, and energy expenditure during exercise vs. recovery in men.
We examined the relationship between energy expenditure (in kcal) and epinephrine (Epi), norepinephrine (NE), and growth hormone (GH) release. Ten men [age, 26 yr; height, 178 cm; weight, 81 kg; O(2) uptake at lactate threshold (LT), 36.3 ml. kg(-1). min(-1); peak O(2) uptake, 49.5 ml. kg(-1). min(-1)] were tested on six randomly ordered occasions [control, 5 exercise: at 25 and 75% of the difference between LT and rest (0.25LT, 0.75LT), at LT, and at 25 and 75% of the difference between LT and peak (1.25LT, 1.75LT) (0900-0930)]. From 0700 to 1300, blood was sampled and assayed for GH, Epi, and NE. Carbohydrate (CHO) expenditure during exercise and fat expenditure during recovery rose proportionately to increasing exercise intensity (P = 0.002). Fat expenditure during exercise and CHO expenditure during recovery were not affected by exercise intensity. The relationship between exercise intensity and CHO expenditure during exercise could not be explained by either Epi (P = 1.00) or NE (P = 0.922), whereas fat expenditure during recovery increased with Epi and GH independently of exercise intensity (P = 0. 028). When Epi and GH were regressed against fat expenditure during recovery, only GH remained statistically significant (P < 0.05). We conclude that a positive relationship exists between exercise intensity and both CHO expenditure during exercise and fat expenditure during recovery and that the increase in fat expenditure during recovery with higher exercise intensities is related to GH release.
Adult↗
Pediatric pharmacodynamics of midazolam oral syrup. Pediatric Pharmacology Research Unit Network.
In this study, the authors evaluate the pharmacodynamics, safety, and acceptability of a new cherry-flavored oral syrup formulation of midazolam. This randomized, double-blind, parallel-group, dose-ranging clinical trial of oral midazolam was conducted at seven U.S. health care institutions focused on pediatric clinical pharmacology research (i.e., the PPRU Network). Pediatric patients (n = 85, ages 6 months through 15 years) underwent invasive procedures and were randomized to a single oral dose of midazolam syrup (0.25, 0.5, or 1.0 mg/kg). Patient taste acceptability of midazolam syrup was evaluated at the time of oral administration. Pharmacodynamic measurements included (1) sedation score using a 5-point scale at baseline and 10-, 20-, and 30-minute postdose intervals and (2) anxiety score using a 4-point scale at the time of separation from caretakers and, when applicable, at the time of mask anesthetic induction. Midazolam and alpha-hydroxymidazolam plasma concentrations were measured at all pharmacodynamic measurement time points. Adverse events were monitored continuously during the study. Most patients (99%) accepted the syrup without difficulty. Satisfactory sedation was achieved within 30 minutes by 81% of patients. The anxiety score at the time of caretaker separation and mask anesthetic induction was satisfactory for 87% and 91% of patients, respectively. A significant linear relationship between plasma drug concentration and maximal sedation score, but not anxiety score, was observed. The occurrence of adverse events was consistent with the known safety profile of midazolam. The most commonly reported adverse events were hiccoughing, hypoxemia, nausea, and emesis. It was concluded that a new oral syrup formulation of midazolam, 0.25 to 1.0 mg/kg, effectively induced rapid-onset, dose-related, adequate, and safe sedation and anxiolysis in pediatric patients who underwent operative procedures. Sedative effects were related to plasma concentrations of both midazolam and the primary metabolite, alpha-hydroxymidazolam. Oral midazolam, 1.0 mg/kg, administered within 30 minutes of the expected procedure or anesthetic induction should provide safe and effective sedation to a majority of children ages 6 months to 16 years.
Administration, Oral↗
The effect of training and epinephrine infusion on ratings of perceived exertion (RPE).
Seven untrained males (mean age [+/-SD] = 25.6+/-3.9 yr, mean ht = 177.0+/-5.9 cm, mean wt = 65.8+/-7.4 kg) completed a 6-week exercise program (cycle ergometer). Prior to training, and at the end of each week of training, each subject performed a 20 min constant-power exercise test (absolute power was the same each week). At the end of the six week training program (within a few days), an additional 20 min constant-power test was performed, during which epinephrine was infused at a rate of 100 ng x kg(-1) x min(-1) over the final 10 min of exercise. Training significantly (P<0.05) reduced end-exercise ratings of perceived exertion (RPE), plasma epinephrine concentration [Epi], plasma norepinephrine concentration [NE], blood lactate concentration [La-], minute ventilation (V(E)), heart rate (HR), and blood glucose concentration [Glc]. Epinephrine infusion failed to increase RPE despite significant (p < 0.05) increases in [Epi], [La-], V(E) and [Glc]. Therefore, the present data indicate that RPE during exercise is not causally related to changes in plasma [Epi]. It also appears that modest changes in plasma [NE], blood [La-], V(E) and blood [Glc] during constant-power cycle ergometry (as observed during Epi infusion) do not impact RPE.
Adrenergic Agonists↗
Antibiotic restriction does not alter endemic colonization with resistant gram-negative rods in a pediatric intensive care unit.
OBJECTIVE: To test whether a ceftazidime restriction policy in a pediatric intensive care unit (ICU) could decrease the endemic rate of colonization with ceftazidime-resistant gram-negative bacilli. DESIGN: Prospective, pre- vs. postintervention study. SETTING: University hospital pediatric ICU. PATIENTS: Consecutive children admitted to the pediatric ICU over a 19-mo period. INTERVENTIONS: After an observation period in which antibiotic use was not controlled, ceftazidime was prohibited unless the patient's microbiological results indicated that the drug was necessary for cure. Aminoglycoside use was not regulated. The size of the endemic reservoir of ceftazidime- and tobramycin-resistant organisms was determined by daily nasopharyngeal and rectal swab specimens obtained on all admissions to the ICU. MEASUREMENTS AND MAIN RESULTS: Despite a 96% reduction in ceftazidime use, the incidence density (number of isolates/100 patient-days) of ceftazidime-resistant organisms increased through the course of the study, from 1.57 to 2.16. The incidence density of tobramycin-resistant organisms was unchanged. Ceftazidime restriction resulted in a small but nonsignificant decrease in the proportion of ceftazidime-resistant organisms acquired late (beyond 72 hrs) in the patients' ICU course (56.5% vs. 45.9%). However, there was a more substantial decrease in the proportion of ceftazidime-resistant organisms derived from species known to harbor derepressible amp C beta-lactamases (68.2% vs. 45.9%, p < .05). CONCLUSIONS: These data indicate that antibiotic restriction policies in an ICU fail to diminish the size of the endemic reservoir of antibiotic-resistant gram-negative rods, and suggest that such policies in the absence of broader efforts to limit antibiotic use will have little impact.
Anti-Bacterial Agents↗
Clinical perspectives on sinusitis and otitis media.
As the leading cause of physician office visits and loss of time from school as well as the cause of significant morbidity among young children, respiratory infections impose a major burden on the health care system. The most common causative pathogens are Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis. In young children acute otitis media and sinusitis may present with relatively nonspecific symptoms such as irritability. Older children may complain of more specific problems; for example those with otitis media may complain of otalgia. Upper respiratory tract infections are typically diagnosed by signs and symptoms and treated empirically with an antimicrobial agent that offers coverage of the usual causative respiratory pathogens.
Child↗
Serum sertraline and N-desmethylsertraline levels in breast-feeding mother-infant pairs.
OBJECTIVE: The authors' goal was to study the serum sertraline levels of breast-feeding mothers and their infants. METHOD: They obtained serum levels of sertraline and N-desmethylsertraline in nine mother-infant pairs. RESULTS: Sertraline levels were very low (less than 2 ng/ml) in seven of the nine infants and low (3 ng/ml) in one. N-Desmethylsertraline levels were also low (6 ng/ml or less) in seven of the nine infants. One infant had a high level of N-desmethylsertraline, and one infant had unusual serum sertraline and N-desmethylsertraline values (half of its mother's levels). All infants were thriving. CONCLUSIONS: Most breast-feeding infants whose mothers were taking sertraline had very low serum levels of both sertraline and N-desmethylsertraline, consistent with published reports. The authors discuss in detail the one infant with unusually high levels.
1-Naphthylamine↗
Cefprozil treatment of persistent and recurrent acute otitis media.
OBJECTIVE: We identified the pathogens causing persistent and recurrent acute otitis media (AOM) and the clinical efficacy of cefprozil as treatment. STUDY DESIGN: This was a noncomparative, open label multicenter trial. Children ages 6 months to 12 years with signs and symptoms of AOM and evidence of middle ear effusion, as confirmed by pneumatic otoscopy or tympanometry, underwent tympanocentesis and subsequent treatment with cefprozil (15 mg/kg given twice daily) for 10 days. Patients with recurrent otitis media or failure of previous antibiotic therapy or prophylaxis were particularly sought for the study. RESULTS: Two hundred sixty-two (99%) of 265 enrolled children were considered evaluable. The median age of the study group was 1 year. Ninety-eight (37%) of the children had a history (within 30 days) of prior antibiotic use. Ninety-seven (37%) met our definition of recurrent AOM, 48 (18%) met our definition of persistent AOM and 132 (50%) children had 3 or more previous episodes of acute otitis media within 12 months before study. Eighty-two (31%) of the enrollment tympanocentesis had no growth, 150 (57%) had a single bacterial pathogen and 29 (11%) had multiple bacterial pathogens. Of the 93 Streptococcus pneumoniae pretreatment isolates, 50 (54%) were penicillin-susceptible, 12 (13%) were penicillin-intermediate resistant and 31 (33%) were penicillin-resistant. Of the 75 Haemophilus influenzae pretreatment isolates, 42 (56%) produced beta-lactamase as did 4 (27%) of the 15 Moraxella catarrhalis strains. A satisfactory clinical response by pathogen was found in 75% (70 of 93) with S. pneumoniae, 75% (56 of 75) with H. influenzae and 93% (13 of 14) with M. catarrhalis; the response with single pathogen infections was higher than those with multiple pathogens (118 of 150 (78%) and 17 of 29 (59%), respectively; P = 0.03). The response for patients with isolates of S. pneumoniae that were penicillin-susceptible, -intermediate or -resistant were 39 of 50 (78%), 11 of 12 (92%) and 21 of 31 (68%), respectively. Older children had a satisfactory clinical outcome more frequently than younger children (P < 0.001), and the response to therapy varied for persistent, recurrent and recently untreated AOM (P < 0.01). CONCLUSION: Persistent and recurrent AOM involves the same pathogens as recently untreated AOM but bacteria with reduced antibiotic susceptibility may be more frequently present. This noncomparative study suggests that cefprozil 30 mg/kg/day given in two divided doses for 10 days may be effective in the treatment of children with persistent and recurrent AOM.
Acute Disease↗
Pharmacokinetics of ceftriaxone.
Ceftriaxone fulfills many of the qualities of an ideal antibiotic: a prolonged elimination half-life, which results from a "restrictive" excretion pattern; saturable protein binding, which provides the theoretical basis for administering the total daily dose as a single bolus; and once-a-day dosing, which provides plasma and tissue concentrations that exceed the MIC for most susceptible pathogens for 24 hours.
Bacterial Infections↗
Antiemetic efficacy and pharmacokinetic analyses of the serotonin antagonist ondansetron (GR 38032F) during multiple-day chemotherapy with cisplatin prior to autologous bone marrow transplantation.
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Adult↗
Comparison of piperacillin alone versus piperacillin plus tobramycin for treatment of respiratory infections in children with cystic fibrosis.
Seventeen patients with cystic fibrosis (CF) and pulmonary exacerbations were randomly assigned to two treatment groups: piperacillin 600 mg/kg/day (P), and piperacillin 600 mg/kg/day plus tobramycin (PT), in order to determine the safety and pharmacokinetics of high-dose piperacillin and whether piperacillin alone was effective for the treatment of Pseudomonas infections. The mean half-life of piperacillin was 0.54 hours, with a peak concentration of 232 micrograms/ml. No differences between P and PT groups were noted in clinical assessment, as judged by Shwachman scores, pulmonary function testing, or weight gain. However, during the course of treatment, quantitative sputum cultures decreased by greater than 10(2) colony-forming units in only 5 out of 19 Pseudomonas isolates from the P group, compared with 12 of 19 isolates from the PT group (P less than 0.03, Chi-square). Although emergence of resistance was not seen, one isolate had an increase in minimum inhibitory concentration from 8 to 128 micrograms/ml. There were no serious adverse reactions to piperacillin; only one patient developed fever possibly related to piperacillin. Therapy with high-dose piperacillin was safe in children with CF. Treatment with piperacillin alone was less effective than combination therapy with gentamicin for reduction in titer of Pseudomonas in sputum. However, the role of antimicrobial agents in the treatment of CF remains undefined. A double-blind placebo-controlled trial is indicated.
Child↗
Screening for the developmental toxicity of retinoids: use of the sea urchin model.
Retinoids are being used increasingly in dermatologic practice. Fetal malformation is a major form of toxicity associated with certain retinoids. In this study, the developmental toxicity of isotretinoin, its metabolites, and a structurally related analog, tretinoin, were evaluated using the sea urchin model. The American sea urchin, Arbacia punctulata, completes its major developmental stages within 24 hr and has been previously utilized for screening human teratogens. The parent compound, isotretinoin, induced dose-dependent delayed rather than dysmorphic development of the sea urchin embryo. In contrast, its metabolites, 4-oxo-isotretinoin and 4-oxo-tretinoin, and the analog tretinoin induced strikingly dysmorphic development. This may indicate that the metabolites of isotretinoin, rather than the parent compound, may be responsible for the fetal abnormalities observed in the "isotretinoin teratogen syndrome." Therefore, the sea urchin model might serve as a discriminating and rapid screening test for identifying other potential developmentally toxic retinoids.
Animals↗
Amiodarone: correlation of serum concentration with suppression of complex ventricular ectopic activity.
Although amiodarone has been used for the suppression of complex ventricular arrhythmias since the early 1970s, there is a paucity of information regarding the relation of serum concentration to arrhythmia suppression. To investigate this relation, 25 patients receiving chronic amiodarone therapy for complex ventricular arrhythmias were retrospectively studied. At each visit a blood sample for determination of trough serum amiodarone concentration and a 24-hour 2-channel ambulatory electrocardiogram (ECG) were obtained. Dosage was adjusted, based on the ambulatory ECG, to maintain arrhythmia suppression at the lowest possible amiodarone dose and, hence, because of the extremely long half-life of amiodarone, patients were rarely in a true steady state. Over 17 months, 218 ambulatory ECGs with corresponding serum samples were analyzed. Negative correlations between serum amiodarone concentration and the frequencies of premature ventricular complexes (PVCs), paired PVCs and ventricular tachycardia were found (p less than 0.005, p less than 0.005 and p less than 0.05, respectively). No correlations existed between amiodarone dose and these arrhythmias. Trough serum amiodarone concentrations greater than 2.0 micrograms/ml were associated with significant reductions in the frequencies of PVCs (p less than 0.01) and paired PVCs (p less than 0.02) when compared with serum concentrations below this level. A reduction in ventricular tachycardia was seen with serum concentrations greater than 1.5 micrograms/ml (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
Amiodarone↗
Amiodarone: intravenous loading for rapid suppression of complex ventricular arrhythmias.
A major disadvantage of conventional amiodarone therapy is the long delay between initiation of therapy and arrhythmia suppression. In this study, the hypothesis was tested that complex ventricular arrhythmias would be suppressed rapidly by an intravenous amiodarone infusion designed to achieve and maintain a therapeutic serum concentration. Eleven patients were studied. Each underwent a single intravenous dose kinetic study, followed by a two stage infusion of amiodarone that achieved and maintained a serum concentration of 2 to 3 micrograms/ml. In seven patients, arrhythmias during hours 24 to 48 after the infusion were compared with arrhythmias without therapy. Amiodarone therapy reduced episodes of ventricular tachycardia by 85% (p less than 0.01), paired premature ventricular complexes by 74% (p less than 0.01) and premature ventricular complexes by 60% (p less than 0.05). Four patients could not tolerate a control period without therapy because of symptomatic arrhythmias. In three patients, symptomatic arrhythmias were abolished during the 24 hour evaluation period. Two of 11 patients, both with severe left ventricular dysfunction, developed significant hypotension during the loading phase of the infusion. It is concluded that the achievement and maintenance of a therapeutic serum concentration of intravenous amiodarone are effective in the rapid suppression of life-threatening ventricular arrhythmias. Caution should be employed when using large intravenous doses in patients with severely impaired left ventricular function.
Administration, Oral↗
The convulsant potency of lidocaine and its N-dealkylated metabolites.
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Acetanilides↗