Biomedical subjects

D A Kuhl

Publications and source records attributed to D A Kuhl.

At least 19 recordsLinked to original sources

PubMed2000

Sequential single doses of cisapride, erythromycin, and metoclopramide in critically ill patients intolerant to enteral nutrition: a randomized, placebo-controlled, crossover study.

OBJECTIVE: To evaluate the comparative efficacy of enteral cisapride, metoclopramide, erythromycin, and placebo for promoting gastric emptying in critically ill patients with intolerance to gastric enteral nutrition (EN). DESIGN: A randomized, crossover study. SETTING: Adult medical intensive care unit at a university-affiliated private hospital and trauma intensive care unit at a university teaching hospital. PATIENTS: Ten adult, critically ill, mechanically ventilated patients not tolerating a fiber-containing EN product defined as a single aspirated gastric residual volume >150 mL or two aspirated gastric residual volumes >120 mL during a 12-hr period. INTERVENTIONS: Patients received 10 mg of cisapride, 200 mg of erythromycin ethylsuccinate, 10 mg of metoclopramide, and placebo as 20 mL of sterile water every 12 hrs over 48 hrs. Acetaminophen solution (1000 mg) was administered concurrently. Gastric residual volumes were assessed, and plasma acetaminophen concentrations were serially determined by TDx between 0 and 12 hrs to evaluate gastric emptying. MEASUREMENTS AND MAIN RESULTS: Gastric residual volumes during the study were not significantly different between agents. No differences in area under the concentration vs. time curve or elimination rate constant were identified between agents. Metoclopramide and cisapride had a significantly shorter mean residence time of absorption than erythromycin (6.3+/-4.5 [SEM] mins and 10.9+/-5.8 vs. 30.1+/-4.5 mins, respectively [p<.05]). Metoclopramide (9.7+/-15.3 mins) had a significantly shorter time to peak concentration compared with erythromycin and placebo (60.7+/-8.1 and 50.9+/-13.5 mins, respectively [p<.05]). The time to onset of absorption was significantly shorter for metoclopramide vs. cisapride (5.7+/-4.5 vs. 22.9+/-5.7 mins [p<.05]). CONCLUSION: In critically ill patients intolerant to EN, single enteral doses of metoclopramide or cisapride are effective for promoting gastric emptying in critically ill patients with gastric motility dysfunction. Additionally, metoclopramide may provide a quicker onset than cisapride.

Acetaminophen↗

PubMed2000

Gender differences in metered-dose inhaler-spacer device technique.

STUDY OBJECTIVE: To determine whether gender affects the correct use of a metered-dose inhaler (MDI)-spacer device. DESIGN: Prospective, observational study. SETTING: University classrooms. PATIENTS: Eighty-three students in their third year of a Doctor of Pharmacy program. INTERVENTION: Students were given the device and received 20 minutes of education on its use. They then were asked to perform the technique. Assessment and retraining were done, as necessary, by clinicians who were experienced with the device. Students returned 1 week later to perform the technique again. MEASUREMENTS AND MAIN RESULTS: The performance of men versus women was analyzed with chi 2 tests and the Student's t test. Power analysis indicated that 30 students were needed in each group. CONCLUSION: There were no significant differences between men and women in proper MDI-spacer technique.

Adult↗

PubMed1999

Prolonged opioid antagonism with naloxone in chronic renal failure.

Respiratory depression secondary to morphine intoxication occurred in an elderly patient with chronic renal failure (CRF). It was reversed with a continuous infusion of naloxone. Approximately 11 hours after the infusion was discontinued, the patient relapsed into respiratory depression consistent with opioid intoxication. He was rechallenged with a naloxone infusion with resolution of the opioid effects. This case suggests prolonged antagonism of opioid effects inconsistent with naloxone's reported pharmacologic effects. Serum naloxone concentrations measured after the end of the infusion suggest that the drug's pharmacokinetics were significantly altered. Further research is necessary to characterize pharmacokinetic changes that occur in CRF. In the absence of this information, similar patients should be closely monitored for relapse of respiratory depression after naloxone is discontinued.

Aged↗

PubMed1998

Alterations in N-acetylation of 3-methylhistidine in endotoxemic parenterally fed rats.

N-methylhistidine (3-meH) is endogenously released during muscle catabolism and serves as a marker of protein turnover. In rats > 85% of 3-meH is excreted in the urine as the N-acetyl derivative. It has been reported that the percent of non-acetylated 3-meH (NA-3-meH) varies minimally with stress. To further evaluate these reports we randomized 39 male Sprague-Dawley rats (157-213 g) to receive parenteral nutrition only (PN) or PN plus continuous infusion of Escherichia coli 026:B6 lipopolysaccharide at 6 (LPS-6) or 12 (LPS-12) mg.kg-1.d-1 for 48 h. All animals received isocaloric and isonitrogenous PN 24 h before and throughout the study with water ad libitum. Total 3-meH excretion was significantly increased (P < 0.05) in the LPS-6 (470 +/- 136 micrograms/48 h) and LPS-12 (557 +/- 171 micrograms/48 h) groups versus the PN (331 +/- 126 micrograms/48 h) group. NA-3-meH differed significantly between the LPS-12 (218 /+- 89 micrograms/48 h, LPS-6 (94 +/- 48 micrograms/48 h), and PN (39 +/- 12 micrograms/48 h) groups (P < 0.05). Percent NA-3-meH increased significantly from 12.7 +/- 3.9% in the PN group to 19.8 +/- 8.0 and 39.9 +/- 12.8% in the LPS-6 and LPS-12 groups, respectively (P < 0.05). No significant changes in acetyl 3-meH were found between groups. These data suggest that either saturation or inhibition of acetylation pathways occurs with increasing levels of stress. Due to the disproportionate increases in NA-3-meH and percent NA-3-meH during endotoxemia, only total 3-meH should be used as an indicator of protein turnover in rats.

Acetylation↗

PubMed1997

The effect of alpha-adrenergic antagonism upon nitrogen loss during endotoxemia.

Sixty male Sprague-Dawley rats were randomized to receive parenteral nutrition (PN) only; PN plus continuous infusion of Escherichia coli 026:B6 lipopolysaccharide (PN + LPS) at 6 mg.kg-1.d-1; or PN plus LPS plus a continuous infusion of the alpha-adrenergic antagonist phentolamine (PN + LPS + PHEN) at 5 mg.kg-1.d-1 or 20 mg.kg-1.d-1 for 48 h. All animals received isocaloric, isonitrogenous PN. LPS significantly lowered nitrogen balance (mmol/48 h) from PN control; however, addition of PHEN substantially worsened nitrogen balance compared with LPS (14.2 +/- 3, 2.4 +/- 5.2, -1.6 +/- 4.5, -0.8 +/- 5.4, for the PN, PN + LPS, PN + LPS + PHEN5 and PN + LPS + PHEN20 groups, respectively; P < 0.0001). Urinary 3-methylhistidine/creatinine ratio (3-meH/creat) paralleled the nitrogen balance data (0.30 +/- 0.09, 0.45 +/- 0.12, 0.51 +/- 0.14, 0.60 +/- 0.12, respectively; P < 0.0001). The high-dose PHEN resulted in 82 +/- 9% blockade. To ascertain if any beneficial effect upon body protein loss is achieved during severe stress, 30 rats were given PN + LPS at 12 mg.kg-1.d-1 or PN + LPS12 + PHEN20. These data showed similar changes in nitrogen balance and 3-methylhistidine/creatinine with the use of PHEN during severe endotoxemia. alpha-adrenergic antagonism with PHEN worsens body protein loss as measured by nitrogen balance and 3-methylhistidine/creatinine in PN-fed endotoxemic rats.

Adrenergic alpha-Antagonists↗

PubMed1997

Dose-dependent effect of octreotide on nitrogen retention and glucose homeostasis in response to endotoxemia in parenterally fed rats.

OBJECTIVE: This study compared the effect of different doses of octreotide on glucose and protein homeostasis in rats receiving concomitant lipopolysaccharide and parenteral nutrition infusions. METHODS: Sixty-six male Sprague Dawley rats (185 to 220 g) were randomized to receive parenteral nutrition only (PN), PN plus continuous infusion of Escherichia coli 026:B6 lipopolysaccharide at 6 mg/kg/day (LPS), PN plus LPS plus octreotide at 10 micrograms/kg/day (LPS + Oct 10), 100 micrograms/kg/day (LPS + Oct 100), or 1000 micrograms/kg/day (LPS + Oct 1000) for 48 hours. Prior to randomization all animals received isocaloric and isonitrogenous PN (170 kcal/kg/day as glucose and 1.1 g N/kg/day) and were kept nil per os except for water ad libitum. Nitrogen balance, urinary 3-methylhistidine/creatinine ratio, serum glucose concentration, and incidence of glycosuria were compared between groups. Serum urea nitrogen (SUN) changes were incorporated into the cumulative 48 hour nitrogen balance. ANOVA, Duncan's multiple range test, and Fisher's Exact Test were used for statistical analysis. RESULTS: Nitrogen balance (mg/48 hours) was significantly lower in all four groups receiving LPS +/- Oct when compared to the control group receiving PN alone. SUN (mg/dL) was significantly higher in all four groups receiving LPS +/- Oct when compared to control. There were no statistically significant differences in nitrogen balance or SUN among the four groups receiving LPS +/- Oct. The ratio of urinary 3-methylhistidine/ creatinine was significantly higher in the LPS + Oct 1000 group compared to the PN group (0.77 +/- 0.37 vs. 0.42 +/- 0.24, p < 0.05). Serum glucose concentrations and incidence of glycosuria among the five groups were not significantly different. CONCLUSIONS: Endotoxin significantly reduces nitrogen balance compared to controls fed PN. Octreotide does not significantly improve nitrogen retention or glucose homeostasis in endotoxemic parenterally fed rats.

Animals↗

PubMed1997

Recovery from ischemic acute renal failure is improved with enteral compared with parenteral nutrition.

OBJECTIVE: To compare measurements of renal function after acute ischemic renal failure in rats fed enterally or parenterally. DESIGN: Prospective, randomized, animal trial. SETTING: University research laboratory. SUBJECTS: Male Sprague-Dawley rats (n = 21). INTERVENTIONS: Animals were randomized to receive isocaloric (160 nonprotein kcal/kg/day), or isonitrogenous (1.4 g of nitrogen/kg/day [100 mmol/kg/day]) enteral (n = 10), or parenteral nutrition (n = 11) through either a gastrostomy tube or a catheter placed in the jugular vein. After the animals received 7 days of assigned feedings, baseline blood samples were collected. A right nephrectomy and 45-min left renal pedicle occlusion were then performed. One hour after the ischemic injury, assigned feedings were resumed and continued for 3 days. After ischemic injury, daily blood samples were obtained and 24-hr urine collections were performed. On day 11, animals were killed and the kidney was harvested and fixed for subsequent microscopic examination. MEASUREMENTS AND MAIN RESULTS: Urine was analyzed for concentrations of total urea nitrogen, creatinine, protein, and calcium. Serum was analyzed for creatinine and urea nitrogen concentrations. Fixed kidney sections were examined for mitotic figures, tubular calcifications, and casts using light microscopy by an investigator blinded to the nutritional regimen. Data are presented as mean +/- SD or median (range). Percent increase in creatinine clearance from the nadir on day 9 to day 11 was approximately 2.5-fold greater in the enteral compared with the parenteral nutrition group (490 +/- 221% vs. 208 +/- 130%; p = .003). Histologic evaluation demonstrated greater dystrophic tubular calcifications per ten high-power fields in the parenteral compared with the enteral nutrition group (50 [four to 85] vs. three [0 to 37]; p = .001). No differences in urine calcium concentration or 24-hr calcium excretion were seen. CONCLUSION: Rats given continuous enteral nutrition 7 days before and for 3 days after ischemic acute renal failure have improved renal function compared with rats given parenteral nutrition.

Acute Kidney Injury↗

PubMed1996

Standardization of acid hydrolysis procedure for urinary 3-methylhistidine determination by high-performance liquid chromatography.

The N-acetylated form of N-methylhistidine (3-methylhistidine, 3-meH), a non-invasive marker of proteolysis, accounts for 80-90% of total 3-meH excretion (acetylated+non-acetylated 3-meH) in the rat. To determine total 3-meH excretion, samples require acid hydrolysis prior to determination by high-performance liquid chromatography. This study evaluated the stability of 3-meH at various times and temperatures of hydrolysis and determined the optimal conditions for hydrolysis of samples. Increasing temperature (120 degrees C) results in significant degradation of 3-meH with no appreciable change in concentration being noted at 80 degrees C. Hydrolysis at 100 degrees C for 1.5 to 4 h or 80 degrees C for 8 to 12 h is recommended for determining total 3-meH concentrations in rat urine.

Animals↗

PubMed1996

Fluoro-deoxyglucose positron emission tomography in diffuse Lewy body disease.

We report six demented individuals with pathologically verified diffuse Lewy body disease (DLBD) studied with fluoro-deoxyglucose positron emission tomography (FDG-PET). Three subjects had pure DLBD and three subjects had combined DLBD and Alzheimer's disease (DLBD-AD) pathology. FDG-PET revealed evidence of diffuse cerebral hypometabolism in both pure DLBD and DLBD-AD with marked declines in association cortices with relative sparing of subcortical structures and primary somatomotor cortex, a pattern reported previously in AD. Unlike AD, however, these subjects also had hypometabolism in the occipital association cortex and primary visual cortex. These findings indicate the presence of diffuse cortical abnormalities in DLBD and suggest that FDG-PET may be useful in discriminating DLBD from AD antemortem.

Aged↗

PubMed1995

The effect of insulin-like growth factor-1 on protein metabolism and hepatic response to endotoxemia in parenterally fed rats.

To determine the influence of insulin-like growth factor-1 (IGF-1) on nitrogen loss and hepatic response to critical illness, 34 male Sprague-Dawley rats (190-230 g) were randomized to receive parenteral nutrition (PN) only (Ctrl), PN plus continuous infusion of Escherichia coli 026:B6 lipopolysaccharide at 6 mg/kg/day (LPS), or PN plus LPS plus rhIGF-1 (IGF-1) at 3 mg/kg/day for 48 hr. Prior to randomization, all animals underwent iv cannulation and 30 hr of adaptation to PN. All animals received isocaloric and isonitrogenous PN (glucose 170 kcal/kg/day and nitrogen 1.1 g/kg/day) and were kept NPO except for water ad libitum. [15N]glycine was infused in all animals for determination of liver fractional synthetic rate. Cumulative nitrogen balance during endotoxemia was significantly different from each other (+72 +/- 42, -217 +/- 131, -114 +/- 137 mg/kg/48 hr for the Ctrl, LPS, and IGF-1 groups, respectively; ANOVA, P < 0.001). Endotoxin significantly increased the urinary 3-methylhistidine/creatinine ratio (0.24 +/- 0.05, 0.55 +/- 0.12, 0.48 +/- 0.17 for the Ctrl, LPS, and IGF-1 groups, respectively; ANOVA, P < 0.001); however, IGF-1 did not significantly reduce the ratio. Endotoxin induced a significant increase in liver fractional synthetic rate (29 +/- 8, 56 +/- 18, 64 +/- 12%/day for the Ctrl, LPS, and IGF-1 groups, respectively; ANOVA, P < 0.01) and depressed hepatic cytochrome P450 concentration (0.54 +/- 0.19, 0.22 +/- 0.07, 0.19 +/- 0.07 nmol/mg protein, respectively; ANOVA, P < 0.05) and ethoxycoumarin O-deethylase (ECOD) activity (103 +/- 73, 29 +/- 13, 17 +/- 11, pmol/mg/min, respectively; ANOVA, P < 0.01); however, rhIGF-1 did not significantly alter these hepatic variables during endotoxin infusion. Recombinant human insulin-like growth factor-1 significantly improved nitrogen balance without compromising hepatic response as measured by liver fractional synthetic rate, cytochrome P450 concentration, and ECOD activity in endotoxemic parenterally fed rats.

7-Alkoxycoumarin O-Dealkylase↗

PubMed1994

Beta-agonists in the treatment of acute exacerbation of chronic obstructive pulmonary disease.

OBJECTIVE: To critically evaluate the following issues regarding the use of beta-agonists in the treatment of acute exacerbations of chronic obstructive pulmonary disease (COPD): (1) optimal dose, (2) use of nebulizer (NEB) versus metered-dose inhaler-spacer devices (MDISs), (3) comparison with anticholinergic agents, and (4) use in mechanically ventilated patients. The patient populations addressed are limited primarily to emergency department (ED) and intensive care/acute care settings. DATA SOURCES: English-language journal articles published between 1977 and 1993. STUDY SELECTION: Nine studies were evaluated that included beta-agonists alone or in combination with other bronchodilators in the treatment of acute exacerbation of COPD. Many of the studies contained design flaws or were limited in size, making interpretation difficult. In studies containing both asthma and COPD patients, focus was restricted to analysis of COPD patients when possible. DATA EXTRACTION: Performed subjectively by the authors. Studies were evaluated for methodologic strengths and weaknesses. DATA SYNTHESIS: Dosing studies in patients with stable disease show a relationship between dose and the various pulmonary function tests (PFTs). Dose also correlates with duration of action and incidence of adverse effects. Four studies compared NEBs versus MDISs. Studies revealed significant improvement in PFTs for both treatments, with no significant difference between groups noted. Five studies compared various combinations of beta-agonists and ipratropium. Both ipratropium and beta-agonists caused statistically significant increases in PFTs from baseline. Combination therapy provided no further increase in spirometry compared with that of single-agent therapy. One study did report an early discharge from the ED with the addition of ipratropium. Most studies did not use large doses of beta-agonists or evaluate the effect of repeated doses. Many studies allowed concomitant therapy. Most did not include outcome measurements, such as ED length of stay, admission rates, hospital stay, or incidence of relapse. CONCLUSIONS: Dose-response studies in patients with stable disease suggest that doses of albuterol powder up to 1 mg may be tolerated safely, although use of repeated larger doses has not been well studied. Beta-agonists given by MDIS or NEB are equally effective in this setting. There is no apparent advantage to combined use of beta-agonist and ipratropium in the acute setting. Future research in this area should evaluate the use of larger or repeated doses of beta-agonists in the acute setting. Optimizing concurrent therapy and evaluating various patient outcomes should receive special attention in further investigations.

Acute Disease↗

PubMed1993

Pneumonia and stress ulceration in severely injured patients. A prospective evaluation of the effects of stress ulcer prophylaxis.

Stress ulcer prophylaxis is a routine aspect of the care of critically injured patients. Recent reports have suggested that patients undergoing prophylaxis with histamine antagonists are predisposed to nosocomial pneumonia, and that treatment with sucralfate can prevent this problem. An open, prospective randomized trial of three regimens was conducted with 278 evaluable patients. The patients were assigned to one of three group: the group receiving sucralfate, the group receiving a cimetidine hydrochloride bolus, and the group undergoing continuous infusion with cimetidine. Stress ulceration developed in 8% of patients in the sucralfate group, 13% of patients in the cimetidine bolus group, and 12% of patients in the cimetidine infusion group, while nosocomial pneumonia developed in 29% of patients in the sucralfate group, 32% of patients in the cimetidine bolus group, and 23% of patients in the cimetidine infusion group. Multivariate analysis of risk factors associated with pneumonia demonstrated independent significance for score on the Glasgow Coma Scale, Injury Severity Score, cord injury, shock, and head injury. Only spinal cord injury was associated with stress ulceration. We conclude that sucralfate and cimetidine are both effective for stress ulcer prophylaxis and that there is no association of cimetidine with nosocomial pneumonia.

Administration, Oral↗

PubMed1992

Pharmacokinetics of systemically administered antibiotics in patients with thermal injury.

Patients who sustain thermal injury may require adjustments of antibiotic dosing because of pharmacokinetic alterations and pathological changes that occur in this patient subset. In general, studies of gentamicin, tobramycin, and amikacin have demonstrated lower elimination half-lives in burn patients than in nonburn patients and healthy volunteers. Other studies have shown a strong correlation between vancomycin clearance and creatinine clearance and the need for higher vancomycin dosages for burn patients than for nonburn patients. Studies of ceftazidime, ticarcillin, enoxacin, and aztreonam have shown increases in the volume of distribution or decreases in the maximum concentration achieved. Total and renal drug clearance of aztreonam was highly correlated with creatinine clearance. With imipenem, the half-life, clearance, and volume of distribution observed in burn patients were not significantly different from those in nonburn patients, although substantial interpatient variability existed. Imipenem clearance was significantly correlated with creatinine clearance. Individualization of antibiotic therapy for burn patients is recommended with use of measured serum concentrations of the antibiotic or creatinine clearance as an estimate of renal function.

Aminoglycosides↗

PubMed1991

Effect of neurotrauma on hepatic drug clearance.

Lorazepam, antipyrine, and indocyanine green were administered to 10 patients with severe head injuries as marker substrates of hepatic glucuronidation, oxidation, and hepatic blood flow, respectively. Pharmacokinetic parameter estimates were determined at baseline (20 to 80 hours after injury) and up to three additional times thereafter (study days 4, 7, and 14). Antipyrine clearance was increased significantly from baseline (0.50 +/- 0.31 ml/min/kg) on study days 4, 7, and 14 (p less than 0.0001). Increases in antipyrine clearance from baseline to the last study day were observed in all study patients ranging from 14% to 207%. A significant increase was also observed in lorazepam clearance on study day 14 relative to baseline (1.39 +/- 0.56 ml/min/kg) (p less than 0.005). Increases in lorazepam clearance occurred in seven of nine patients over time ranging from 9% to 130%. The unbound fraction of lorazepam did not change significantly over the study period. Likewise, no significant change was observed in the clearance of indocyanine green over time. Antipyrine clearance and alpha 1-acid glycoprotein (r = 0.41), and lorazepam clearance and C-reactive protein (r = -0.38) were significantly correlated (p less than 0.05). Similarly, antipyrine and lorazepam clearances were significantly correlated with injury severity based on the Acute Physiologic and Chronic Health Evaluation (APACHE II) score (r = -0.43 and r = -0.37, respectively). These findings suggest that hepatic oxidative and conjugative metabolism increase significantly over time in patients after acute head injury. An awareness of the potential for pharmacokinetic alterations in similarly metabolized drugs used for patients with severe head injuries is recommended.

Adult↗

PubMed1991

The prognostic inflammatory and nutritional index in traumatized patients receiving enteral nutrition support.

The prognostic inflammatory and nutritional index (PINI) is a clinical assessment tool which aggregates serum C-reactive protein (CRP), alpha 1-acid glycoprotein (AAG), prealbumin (PA), and albumin (ALB) concentrations into a single score. This study was conducted to characterize the index and its determinants over time in 15 critically ill trauma patients receiving enteral nutritional support (ENS). Patients received 1.4 g of protein/kg/day and 32 kcal/kg/day for at least 7 days using a nutritionally complete formula supplemented with whey protein. The PINI was calculated at baseline and on days 4, 7, 10, 14, 21, and 28. The PINI decreased significantly from baseline (186 +/- 202) to day 4 (116 +/- 86) and reached a nadir at day 14 (27 +/- 40). Serum CRP concentrations decreased significantly during the study period, while PA and ALB concentrations increased significantly. There was no change in the AAG concentration. Nitrogen balance increased significantly during the study period. The PINI was positively correlated with CRP concentration (r = 0.72, p = 0.0001) and negatively correlated with PA concentration (r = 0.56, p = 0.0004 and nitrogen balance (r = -0.51, p = 0.0018). The PINI decreased significantly during ENS of critically ill trauma patients, influenced primarily by a decrease in CRP concentration. Further studies are needed to characterize the PINI's performance as a prognostic tool.

Adolescent↗

PubMed1990

Algorithm for assessing renal dysfunction risk in critically ill trauma patients receiving aminoglycosides.

A recent retrospective study proposed that the following screening criteria be used in identifying critically ill trauma patients receiving aminoglycosides who are at significant risk to develop renal dysfunction: (1) post-admission shock, (2) minimum serum concentration more than 2 mg/L, and (3) diagnosis of septicemia. The major purpose of the present study was to validate these criteria and design a corresponding algorithm for clinical use. All patients admitted to a trauma intensive care unit and receiving an aminoglycosides was also studied. All patients studied over a 7-month period. A control group not receiving aminoglycosides was also studied. All patients were evaluated for the presence of renal dysfunction (i.e., serum creatinine increase greater than or equal to 0.5 mg/dL). Univariate and multivariate statistical analyses were used to compare potential associated risk factors. The overall renal dysfunction incidence was 10% in the treatment patients (n = 93) versus 5% in the control patients (n = 199) (p = 0.13). Sensitivity and specificity of the screening criteria were 67% and 92%, respectively. The predictive values of a positive and negative test relative to correctly labeling patients at high risk or low risk to develop renal dysfunction were 46% and 96%, respectively. Major risk factors associated with renal dysfunction in the treatment group were post-admission shock, minimum serum concentration more than 2 mg/L, and liver dysfunction. Use of three major risk factors has excellent predictive value in identifying severely traumatized patients at low risk for developing renal dysfunction while receiving aminoglycosides. The modest predictive value of a positive test results in conservative management of patients by avoidance of aminoglycosides, i.e., use of alternative antimicrobial agents.

Acute Kidney Injury↗

PubMed1990

Imipenem pharmacokinetics in patients with burns.

The pharmacokinetics of imipenem were studied in 11 adult patients with severe burns who were receiving a therapeutic regimen of imipenem-cilastatin 500 mg intravenously every 6 hours. Serial blood samples for measuring imipenem and 24-hour urine collections for creatinine clearance (CrCl) were obtained after the initial dose and after multiple dosing. Plasma was assayed for imipenem by use of HPLC. A two-compartment model provided a superior fit to the data compared with a one-compartment model in 9 of the 11 patients. There was no significant difference in any pharmacokinetic parameter between the initial dose and after multiple dosing (p greater than 0.05). Combined mean (+/- SD) parameter estimates for the two dosing periods were as follows: VC, 0.11 +/- 0.06 L/kg; Vss, 0.22 +/- 0.06 L/kg; CL, 12.5 +/- 3.6 L/hr/1.73 m2; t1/2 alpha, 0.18 +/- 0.13 hr; t1/2 beta, 1.12 +/- 0.44 hr. Mean clearance in two patients with creatinine clearance values greater than 150 ml/min/1.73 m2 was 17.7 L/hr/1.73 m2. Mean clearance in two patients with creatinine clearance values less than 50 ml/min/1.73 m2 was 8.5 L/hr/1.73 m2. No pharmacokinetic parameter was significantly different from previously reported parameters in normal volunteers (p greater than 0.05). Creatinine clearance ranged from 17 to 218 ml/min/1.73 m2. Imipenem clearance was significantly related to creatinine clearance (CL = 63 + 0.059 CLCR; r2 = 0.60, p = 0.001). No significant association was found between total body surface area burns and imipenem clearance (p greater than 0.05). Our data suggest imipenem pharmacokinetics in patients with burns are comparable to those in normal volunteers although substantial intersubject variability exists.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1990

Prophylaxis of posttraumatic seizures.

The issue of routine anticonvulsant prophylaxis for early and late posttraumatic epilepsy (PTE) has received much attention in the medical literature. Such problems as lack of standard definitions for early and late PTE, the retrospective design of most studies, the wide variability of inclusion and exclusion criteria, and the varied duration of follow-up make this body of literature extremely difficult to evaluate. Severe head trauma appears to cause injured neurons to become hyperexcitable; this in turn brings about the formation of an epileptogenic focus during the time between trauma and seizure occurrence. Both military and civilian head injury populations have been used to evaluate the incidence of PTE. Early seizures (i.e., less than 7 days) occur in approximately 3-5 percent of the head injury patients in both the military and civilian groups. Factors increasing this incidence include intracranial hematoma, focal neurologic deficits, posttraumatic amnesia (PTA) lasting greater than 24 hours, depressed skull fracture, and age less than 5 years. The incidence of late seizures is directly related to the extent of brain damage. The military population, composed primarily of cases with penetrating head injury, is associated with a late PTE incidence of approximately 30-50 percent. Closed head injuries in the military population involve a 5-15 percent seizure incidence. Late PTE incidence after head injuries in the civilian population is less than 5 percent. Risk factors associated with late PTE include loss of consciousness or PTA lasting greater than 24 hours, dural lacerations, depressed skull fractures, and various computerized tomography deficits. These factors vary slightly between the military and civilian populations.(ABSTRACT TRUNCATED AT 250 WORDS)

Humans↗