Doxapram-mediated Increase in Cardiac Output Reduces Opioid Plasma Concentrations: A Pharmacokinetic/Pharmacodynamic-Pharmacokinetic/Pharmacodynamic Modeling Study in Healthy Volunteers.

Doxapram is an analeptic that induces ventilatory stimulation and increases blood pressure and cardiac output (CO). Its mechanism of action is the blockade of background K+ -channels expressed on type 1 carotid body cells. In the randomized controlled trial, the authors explored the role of the increase in CO by doxapram (plasma concentration (Cp) 1,000-3,500 ng/mL) on the pharmacokinetics (PKs) and pharmacodynamics (PDs) of the potent opioid alfentanil (Cp 100-200 ng/mL). Population PK-PD analyses were performed on the doxapram PK-CO data and the alfentanil PK-antinociception data. The analyses showed that the doxapram-induced increase in CO explained the increase in alfentanil distribution and elimination clearances causing a significant reduction in plasma alfentanil Cp and antinociception. This novel approach in which one PK-PD model effectively drives another PK-PD model highlights the importance of physiological influences on PK and PD of a potent opioid with rapid onset of effect and low clinical margin of safety.

Pure orbital blowout fractures reconstructed with autogenous bone grafts: functional and aesthetic outcomes.

The purpose of this study was to investigate the ophthalmic clinical findings following surgical reconstruction with autogenous bone grafts of pure blowout fractures. A retrospective review of 211 patients who underwent surgical repair of an orbital fracture between October 1996 and December 2013 was performed. Following data analysis, 60 patients who were followed up over a period of 1 year were included. A solitary floor fracture was present in 38 patients and a floor and a medial wall fracture in 22 patients. Comparing preoperative findings between these two groups, preoperative diplopia and enophthalmos were almost twice as frequent in the group with additional medial wall fractures: diplopia 8% and 14% and enophthalmos 18% and 55%, respectively. One year following surgery there was no diplopia present in either group. In the solitary floor fracture group, 3% still had enophthalmos. It can be concluded that at 1 year following the repair of pure orbital floor fractures using autogenous bone, good functional and aesthetic results can be obtained. In the group with both floor and medial wall fractures, no enophthalmos was found when both walls were reconstructed. When the medial wall was left unoperated, 29% of patients still suffered from enophthalmos after 1 year.

The effect of platelet-rich plasma on early and late bone healing using a mixture of particulate autogenous cancellous bone and Bio-Oss: an experimental study in goats.

Platelet-rich plasma (PRP), containing various growth factors, may speed up wound and bone healing. Using osteoconductive alloplastic materials in reconstructive surgery, the amount of autogenous bone needed can be reduced. The purpose of this experiment was to study the effect of PRP on a mixture of autogenous bone and deproteinized bovine bone mineral (Bio-Oss) particles in goats. Four, round, critical size defects were made in the foreheads of 20 goats. In all goats the defects were filled with a mixture of autogenous particulate cancellous bone and (Bio-Oss) particles, in which 1 ml of PRP was added in two of the four defects. The goats were allocated to four subgroups each containing five goats, which were killed after 1, 2, 6 and 12 weeks. The results of the histological and histomorphometric examination showed that early and late bone healing were not enhanced when PRP was used.

The effect of platelet-rich plasma on early and late bone healing: an experimental study in goats.

Four round critical-size defects were made in the foreheads of 20 goats. The defects were filled with autogenous particulate cancellous bone, in which 1 ml of platelet-rich plasma (PRP) was added in two of the four defects of each goat. The goats were divided into four subgroups of five goats each, which were killed after 1, 2, 6 and 12 weeks. The results of histologic and histomorphometric examination showed that early and late bone healing was not enhanced when PRP was used.

Reproducibility of aimed-at profiles.

Would a surgeon always draw the same aimed-at profile when planning the correction of a face with evidently malpositioned jaws? The same 10 profile lines were given to seven maxillofacial surgeons on two occasions at intervals of 6 months. The differences in absolute and proportional vertical measurements were compared. It is shown that the variations between first and second drawing were quite large for individual values. However, even the mean differences per measurement vary between surgeons from 0 to 10%. The drawings for the whole group corresponded reasonably well with the ratios given by Farkas and Munro (1987) but were rather divergent from the 'golden dimensions' proposed by Brons and Mulié (1993). Considering the sometimes significant differences, one is advised not to draw profiles 'off the cuff' but to use a construction system for planning osteotomies.

Profiloplasty: variations in personal views.

There is sometimes controversy among colleagues over treatment plans in orthognathic surgery. This is because there are differing ideas about which part of the facial skeleton should be moved to give an optimal result. A study was therefore set up to obtain insight into the differences between surgeons. Ten unbalanced profile drawings were given to seven experienced surgeons with the request that they draw the profile line which they would like to give these patients. It was acceptable either to draw the profiles 'artistically' off the cuff or to use additional construction lines as long as this was not the profile planning according to Brons and Mulié (1993). The evaluation showed that some surgeons drew profiles which resembled each other to some extent in proportions and inclinations, while others produced variations without any evident regularity and basic concept. The variability per profile was very important in almost all cases. Such discrepancies are not acceptable in a teaching centre.

Differentiation of multiple giant cell lesions, Noonan-like syndrome, and (occult) hyperparathyroidism. Case report and review of the literature.

The history is reported of a boy known to have von Recklinghausen neurofibromatosis and multiple recurrent central giant cell granulomata of the mandible and maxilla. This paper discusses the problem of differentiating multiple central giant cell granulomata, Noonan-like/multiple giant cell lesion syndrome, and brown tumor resulting from (occult) hyperparathyroidism.

Continuous interpleural infusion of bupivacaine for postoperative analgesia after surgery with flank incisions: a double-blind comparison of 0.25% and 0.5% solutions.

Postoperative analgesia, as assessed by visual analogue scale scores (0-10) and patient-controlled analgesia morphine requirements, pulmonary function (forced vital capacity and forced expiratory volume in 1 s), and plasma bupivacaine concentrations were studied in patients receiving interpleural blockade with bupivacaine after surgery with a flank incision. Two groups of 10 patients received either 0.5% or 0.25% bupivacaine, both with epinephrine (5 micrograms/mL). Pain relief was initiated when patients had visual analogue scale scores greater than or equal to 4. Patients received 21 mL of bupivacaine 0.25% or 0.5% in a double-blind fashion. One hour later, a continuous infusion of 5 mL/h of the study solution was started. At the same time, patient-controlled analgesia became accessible to the patients. The onset time of pain relief and the area under the visual analogue scale score-time curves over the first 8 h were similar in both groups. Patient-controlled analgesia morphine use was also similar in the 0.25% (21.3 +/- 14.6 mg) and 0.5% (21.0 +/- 16.0 mg) groups (mean +/- SD). In both groups, forced vital capacity and forced expiratory volume in 1 s improved significantly within 60 min (P less than 0.05). Peak plasma concentrations (Cmax) and the area under the plasma concentration-time curve (AUC) over 24 h were higher (P less than 0.001) in the 0.5% group (Cmax, 1.47 +/- 0.37 micrograms/mL; AUC, 1511 +/- 323 micrograms.mL-1.min) than those in the 0.25% group (Cmax, 0.55 +/- 0.22 micrograms/mL; AUC, 680 +/- 118 micrograms.mL-1.min) (mean +/- SD).(ABSTRACT TRUNCATED AT 250 WORDS)

Uptake of sufentanil, alfentanil and morphine in the lungs of patients about to undergo coronary artery surgery.

We have studied the pulmonary extraction and retention of sufentanil, alfentanil and morphine using a double indicator technique in 30 patients undergoing elective aortocoronary bypass surgery. Patients were allocated to three groups (10 each) to receive sufentanil 43 micrograms, alfentanil 672 micrograms or morphine 1887 micrograms, mixed with indocyanine green as indicator. After sufentanil, mean peak extraction was 93.7% (95% confidence interval 87.1-100.4%) and release occurred after 16.1 (13.8-18.4) s; first-pass retention was 61.1 (51.3-70.9)%. After alfentanil, peak extraction was 67.4 (42.7-92.0)% and release occurred after 9.9 (8.5-11.3) s; first-pass retention was 10.1 (3.5-16.7)%. After morphine, peak extraction was 58.3 (44.4-72.2)% and release occurred after 7.2 (4.4-10.1) s; first-pass retention was 7.1 (-4.7-19.9)%. Both peak extraction and first-pass retention were significantly greater after sufentanil. There was no significant difference in the peak extraction and first-pass retention between alfentanil and morphine.