Fosphenytoin: pharmacokinetics and tolerance of intramuscular loading doses

PURPOSE: Fosphenytoin (FPHT; Cerebyx) is well absorbed when given intramuscularly (IM). All prior pharmacokinetic studies had the first plasma sample obtained 30 min after IM administration. The objectives of this study were to determine the rate and extent of FPHT absorption and to evaluate the tolerability of IM FPHT compared with IM saline. METHODS: This was an open-label, double-blinded study in which patients received 10 mg/kg dose of IM FPHT in one gluteus and IM saline in the other gluteus. Half the patients received saline injection of equal volume to FPHT (up to 19.5 mL); the other half received 2 mL of saline. Neurologic examination, vital signs, PHT blood samples, injection site examination, and subjective pain scores at injection site were obtained before and at timed intervals for 6 h. RESULTS: Total PHT serum concentrations 10 microg/mL were obtained in 5 min in 14.3% of patients and in 26.3% after 10 min. More than half the patients had therapeutic serum concentrations at 30 min; 45.8% of patients reported no pain at either the FPHT or saline injection site. No significant difference in pain was noted between FPHT and saline injection sites at 60 min and thereafter. Early decrease in blood pressure occurred but was not clinically significant. Classic PHT-induced central nervous system (CNS) side effects were evident in one third of patients within 1 h after injection. CONCLUSIONS: (a) IM FPHT is rapidly absorbed (therapeutic levels achieved as early as 5-20 min). (b) IM FPHT is well tolerated by most patients irrespective of injection volume.     

MR imaging as the sole preoperative imaging modality for right hepatectomy: a prospective study of living adult-to-adult liver donor candidates

OBJECTIVE: Our aim was to investigate the feasibility of MR imaging as a comprehensive preoperative imaging test for examination of liver donor candidates for adult-to-adult right lobe transplantation. SUBJECTS AND METHODS: Twenty-five consecutive donor candidates were examined at 1.5 T using a torso phased array coil with breath-hold T1- and T2-weighted imaging of the abdomen, MR cholangiography using T2-weighted turbo spin-echo imaging, and MR angiography and venography of the liver using two interpolated three-dimensional spoiled gradient-echo sequences (average dose of gadolinium contrast material, 0.17 mmol/kg). Images were interpreted for liver parenchymal and extrahepatic abnormalities; measurements of right and left lobe liver volumes; definition of hepatic arterial, portal venous, and hepatic venous anatomy; and definition of the biliary branching pattern. Findings were compared with those of conventional angiography in 13 patients, 11 of whom also had surgical findings for comparison. RESULTS: Nine patients were excluded as candidates for donation on the basis of MR imaging findings that included parenchymal or extrahepatic abnormalities in five patients, vascular anomalies in two, and biliary anomalies in three. Two patients who did not undergo surgery underwent conventional angiography that confirmed MR angiographic findings except for a small (<2 mm) accessory left hepatic artery missed on MR imaging. Of the nine patients who underwent successful right hepatectomy, all MR imaging findings were corroborated intraoperatively. In two patients, right hepatectomy was aborted at laparotomy because of intraoperative cholangiography findings; in one of them, the biliary finding was unsuspected on MR imaging. CONCLUSION: A comprehensive MR imaging examination has the potential to serve as the sole preoperative imaging modality for living adult-to-adult liver donor candidates provided improvements in definition of intrahepatic biliary anatomy can be achieved.     

Functional CT imaging of the acute hyperemic response to radiation therapy of the prostate gland: early experience

PURPOSE: Functional CT can measure perfusion and permeability. We hypothesized that acute changes could be measured in these indexes following radiation therapy (RT) to the prostate gland. METHOD: Twenty-two patients with prostatic cancer were studied before and 1-2 and 6-12 weeks after RT. A single section through the prostate was repeatedly scanned after contrast medium bolus injection. Contrast agent clearance per unit volume (alpha/V) and fractional vascular volume (fvv) were calculated using Patlak graphical analysis. Perfusion was calculated as the ratio between maximal rate of tissue enhancement and peak arterial enhancement. RESULTS: Significant increases in all indexes occurred after RT. Mean perfusion rose from 0.122 to 0.263 ml/min/ml at 1-2 weeks, mean alpha/V increased from 0.0012 to 0.0016 ml/min/ml at 1-2 weeks, and mean fvv increased from 13.7 to 21% at 1-2 weeks. All three indexes remained elevated at 6-12 weeks after the start of RT. CONCLUSION: Functional CT demonstrated an acute hyperemic response following RT to the prostate gland.     

Effect of acute and antecedent hypoglycemia on sympathetic neural activity and catecholamine responsiveness in normal rats

Adrenergic responsiveness to acute hypoglycemia is impaired after prior episodes of hypoglycemia. Although circulating epinephrine responses are blunted, associated alterations in adrenal sympathetic nerve activity (SNA) have not been reported. We examined adrenal nerve traffic in normal conscious rats exposed to acute insulin-induced hypoglycemia compared with insulin with (clamped) euglycemia. We also examined adrenal SNA and catecholamine responses to insulin-induced hypoglycemia in normal conscious rats after two antecedent episodes of hypoglycemia (days -2 and -1) compared with prior episodes of sham treatment. Acute insulin-induced hypoglycemia increased adrenal sympathetic nerve traffic compared with insulin administration with clamped euglycemia (165 +/- 12 vs. 118 +/- 21 spikes/s [P < 0.05]; or to 138 +/- 8 vs. 114 +/- 10% of baseline [P < 0.05]). In additional experiments, 2 days of antecedent hypoglycemia (days -2 and -1) compared with sham treatment significantly enhanced baseline adrenal SNA measured immediately before subsequent acute hypoglycemia on day 0 (180 +/- 11 vs. 130 +/- 12 spikes/s, respectively; P < 0.005) and during subsequent acute hypoglycemia (229 +/- 17 vs. 171 +/- 16 spikes/s; P < 0.05). However, antecedent hypoglycemia resulted in a nonsignificant reduction in hypoglycemic responsiveness of adrenal SNA when expressed as percent increase over baseline (127 +/- 5% vs. 140 +/- 14% of baseline). Antecedent hypoglycemia, compared with sham treatment, resulted in diminished epinephrine responsiveness to subsequent hypoglycemia. Norepinephrine responses to hypoglycemia were not significantly altered by antecedent hypoglycemia. In summary, prior hypoglycemia in normal rats increased adrenal sympathetic tone, but impaired epinephrine responsiveness to acute hypoglycemia. Hence, these data raise the intriguing possibility that increased sympathetic tone resulting from antecedent hypoglycemia downregulates subsequent epinephrine responsiveness to hypoglycemia. Alternatively, it is possible that the decrease in epinephrine responsiveness after antecedent hypoglycemia could be the result of reduced adrenal sympathetic nerve responsiveness.     

Pericardial mesothelioma following mantle field radiotherapy

A 49-year-old female was referred with recurrent pericardial effusion following mantle field radiotherapy for Hodgkin s lymphoma. She underwent video-assisted thoracoscopy and resection of a pericardial window. Intraoperatively she suffered a cardiac arrest and subsequently died in the early postoperative period despite maximal therapy. Pathological examination revealed extensive myocardial fibrosis and multiple nodules of pericardial mesothelioma. The latter has hitherto not been recognised following mediastinal radiation. The cardiac complications of mantle field radiotherapy are discussed.     

Combination of preconditioning and delayed flap elevation: evidence for improved perfusion and oxygenation of the latissimus dorsi muscle for cardiomyoplasty

BACKGROUND: Atrophy and fibrosis of the distal part of the latissimus dorsi muscle (LDM) wrap is a recognized complication of cardiomyoplasty that has been attributed to ischemia. Failure of the muscle wrap contributes to the late attrition seen in clinical cardiomyoplasty. In this study we examined the role of two-staged mobilization and of preconditioning by electrical stimulation on the regional perfusion and oxygenation of the LDM. METHODS: In a rabbit model (n = 36) the LDM was preconditioned as follows: group A muscles received preconditioning in situ; group B muscles were partially mobilized by dividing the intercostal perforators and then preconditioned; and group C muscles were completely mobilized and wrapped around a silicone-rubber mandrel before conditioning. Controls received no conditioning. The preconditioning regimen consisted of 2 weeks of continuous stimulation at 2.5 Hz. At completion of preconditioning the muscles were fully mobilized and mounted on a muscle-testing apparatus. Purpose-built microelectrodes measured regional PO2 and perfusion using a diffusible gas tracer technique. Muscles were weighed and processed for fiber typing and capillary counting. RESULTS: All preconditioned muscles demonstrated fiber transformation, with increased fatigue resistance. Perfusion of preconditioned muscles both at rest and during contraction was higher than control in the proximal part of the muscle. Distal regions of group B muscles had higher perfusion and capillary density than any other group (p < 0.05). Distal regions of group C had the lowest perfusion and capillary density, and showed muscle atrophy and histologic evidence of necrosis. During fatigue testing there was a decrease in the PO2 in the distal regions of the control and group C muscles (p < 0.05), whereas it was maintained at resting levels in both group A and B muscles. CONCLUSIONS: Conditioning in situ improves perfusion of the distal LDM and prevents a fall in tissue PO2 during contraction. Two-stage mobilization further improves distal perfusion and capillary density. In contrast, shortterm elevation followed by conditioning produces impaired distal perfusion, decrease in PO2, and fiber necrosis in the distal muscle. The present study suggests that partial mobilization of the LDM performed at the same time as placement of electrodes for preconditioning may prepare the LDM better for the demands of cardiomyoplasty.     

Aspiration of an oropharyngeal airway during nasotracheal intubation

The oropharyngeal airway (OPA) has been a remarkably safe device since its invention by Guedel in 1933. This plastic device is easily placed in the mouth and used for aiding in mask ventilation. We report a case of the aspiration of an OPA causing near total upper airway obstruction.