Intranasal atomized dexmedetomidine for sedation during third molar extraction.

The purpose of this study was to evaluate the intranasal use of 1.5 µg/kg atomized dexmedetomidine for sedation in patients undergoing mandibular third molar removal. Eighteen patients underwent third molar removal in two surgical sessions. Patients were randomly assigned to receive intranasal water (placebo group) or 1.5 µg/kg atomized dexmedetomidine (group D) at the first session. The alternate regimen was used during the second session. Local anaesthesia was injected 30 min after placebo/sedative administration. Pain from local anaesthesia infiltration was rated on a scale from zero (no pain) to 10 (worst pain imaginable). Sedation status was measured every 10 min by a blinded observer with a modified Observer's Assessment of Alertness/Sedation (OAA/S) scale and the bispectral index (BIS). Adverse reactions and analgesic consumption were recorded. Sedation values in group D were significantly different from placebo at 20-30 min, peaked at 40-50 min, and returned to placebo levels at 70-80 min after intranasal drug administration. Group D displayed decreased heart rate and systolic blood pressure, but the decreases did not exceed 20% of the baseline values. Intranasal administration of 1.5 µg/kg atomized dexmedetomidine is effective, convenient, and safe as a sedative for patients undergoing third molar extraction.

Effect of remifentanil on the hemodynamic responses and recovery profile of patients undergoing single jaw orthognathic surgery.

The aim of this study was to compare fentanyl-based versus remifentanil-based anesthesia with regards to the intraoperative hemodynamic stress response and recovery profiles in patients undergoing Le Fort I osteotomy. Seventeen patients were randomly divided into two groups: patients in the F-group received 2 µg/kg fentanyl intravenously followed by an infusion of 0.03-0.06 µg/kg/min, while patients in the R-group received a 0.5 µg/kg bolus of remifentanil followed by an infusion of 0.0625-0.250 µg/kg/min. Mean arterial pressure and heart rate were recorded at the following points: before anesthetic induction, at endotracheal intubation, 5 min after intubation, at incision, just before the osteotomy, during the osteotomy, during the maxillary fracturing, at suturing, at extubation, 5 min after extubation, and then 15 and 30 min postoperatively. Heart rate and mean arterial pressure were significantly lower in the R-group in comparison to the F-group from t1 to t9 (P<0.05). All measured recovery times were significantly shorter in the R-group (P<0.05). The incidence of postoperative side effects was comparable between groups. Remifentanil-based anesthesia is an appropriate alternative to fentanyl during Le Fort I orthognathic surgery; it promotes hemodynamic stability, blunts the stress response to noxious stimuli, and provides a better recovery profile.

Inhaled methoxyflurane (Penthrox) sedation for third molar extraction: a comparison to nitrous oxide sedation.

BACKGROUND: The aim of this study was to evaluate the use of inhaled methoxyflurane (Penthrox) in the reduction of dental anxiety in patients undergoing mandibular third molar removal in a specialist surgical suite and compare it to the conventional nitrous oxide sedation. METHODS: A prospective randomized, non-blinded crossover design study of 20 patients receiving two types of sedation for their third molar extraction who participated in 40 treatment sessions. At first appointment, a patient was randomly assigned to receive either nitrous oxide sedation or intermittent Penthrox inhaler sedation, with the alternate regimen administered during the second appointment. Peri-procedural vital signs (heart rate and blood pressure) were recorded and any deviations from 20% from the baseline values, as well as any drop in oxygen saturation below 92% were documented. The Ramsay Sedation Scale (RSS) score was recorded every five minutes. Patient cooperation during the procedure, patients' general opinion about the sedation technique, surgeon satisfaction and the occurrence of side effects were all recorded. After the second procedure, the patient was also asked if he or she had any preference of one sedation technique over the other. RESULTS: Levels of sedation were comparable in nitrous oxide and Penthrox sedation sessions. However, at 15 minutes of sedation it was significantly lighter (p < 0.05) in Penthrox. No patient in both regimens reached a RSS deeper than a score of 4. Parameters measured for assessment of sedation (patient cooperation, surgeon satisfaction and patient general opinion about sedation technique) were all similarly comparable for both nitrous oxide and Penthrox. In both sedation sessions, the odour of the inhalational agent was accepted by the patients; half of the patients (10 patients) who received methoxyflurane thought its odour was pleasant. Patients preferred methoxyflurane (Penthrox) inhalation over nitrous oxide sedation (Fisher's Exact test, p < 0.05). Adverse events were minimal. No patient was either deeply sedated or agitated. Blood pressure was within ± 20% from the baseline values. No patient had oxygen saturation less than 92%. Dizziness was the most frequently encountered side effect in both regimens (four patients each). Two patients had bradycardia (HR < 60 beats/minute) when nitrous oxide was used in comparison to one patient with Penthrox sedation. Paraesthesia of fingers and heaviness of the chest was encountered only with nitrous oxide sedation (four patients). Mild self-limited shivering occurred in one patient with Penthrox sedation. CONCLUSIONS: The Penthrox Inhaler can produce a comparable sedation to that of nitrous oxide for the surgical extraction of third molars under local anaesthesia.

IL-1 plays a critical role in oral, but not dermal, wound healing.

Wound healing is a well-orchestrated complex process leading to the repair of injured tissues. After injury, proinflammatory cytokines act as important modulators of the inflammatory process. IL-1 expression has been regarded as necessary for healing; however, its effects have also been implicated in delayed wound repair. Currently, there is no consensus or direct evidence that IL-1 activity plays a central role in the healing process. The present investigation was undertaken to define the role of IL-1R signaling in the healing outcome of an excisional wound in the palate or scalp of mice that had targeted deletions of the IL-1R type 1 (IL-1R1(-/-)) compared with matched wild-type mice. Histomorphometric analysis was undertaken to assess the degree of healing and the recruitment of polymorphonuclear and mononuclear phagocytes. After 14 days, wild-type mice exhibited complete closure of intraoral wounds, while IL-1R1(-/-) animals had only partial closure (50%). In the IL-1R1(-/-) mice, healing tissues exhibited a persistent inflammatory cell infiltrate, which did not occur in wild-type animals. Treatment with antibiotics significantly diminished the persistent inflammatory infiltrate and improved healing in the experimental animals. In contrast to oral wounds, the rate of healing and recruitment of polymorphonuclear cells in scalp wounds was similar in IL-1R1(-/-) and wild-type mice. The present data underscore the importance of IL-1 in wound healing in a challenging environment and identify its principal role in facilitating the healing process by protecting an open wound from bacterial insult. In a less challenging environment, the production of new connective tissue and its coverage by migrating epithelium are minimally affected by the absence of IL-1 activity.

Expression of osteoprotegerin, receptor activator of NF-kappaB ligand (osteoprotegerin ligand) and related proinflammatory cytokines during fracture healing.

Fracture healing is a unique biological process regulated by a complex array of signaling molecules and proinflammatory cytokines. Recent evidence for the role of tumor necrosis family members in the coupling of cellular functions during skeletal homeostasis suggests that they also may be involved in the regulation of skeletal repair. The expression of a number of cytokines and receptors that are of functional importance to bone remodeling (osteoprotegerin [OPG], macrophage colony-stimulating factor [M-CSF], and osteoprotegerin ligand [receptor activator of NF-kappaB ligand (RANKL)]), as well as inflammation (tumor necrosis factor alpha [TNF-alpha] and its receptors, and interleukin-1alpha [IL-1alpha] and -beta and their receptors) were analyzed over a 28-day period after the generation of simple transverse fractures in mouse tibias. OPG was expressed constitutively in unfractured bones and elevated levels of expression were detected throughout the repair process. It showed two distinct peaks of expression: the first occurring within 24 h after fracture and the second at the time of peak cartilage formation on day 7. In contrast, the expression of RANKL was nearly undetectable in unfractured bones but strongly induced throughout the period of fracture healing. The peak in expression of RANKL did not correlate with that of OPG, because maximal levels of expression were seen on day 3 and day 14, when OPG levels were decreasing. M-CSF expression followed the temporal profile of RANKL but was expressed at relatively high basal levels in unfractured bones. TNF-alpha, lymphotoxin-beta (LT-beta), IL-1alpha, and IL-1beta showed peaks in expression within the first 24 h after fracture, depressed levels during the period of cartilage formation, and increased levels of expression on day 21 and day 28 when bone remodeling was initiated. Both TNF-alpha receptors (p55 and p75) and the IL-1RII receptor showed identical patterns of expression to their ligands, while the IL-1R1 was expressed only during the initial period of inflammation on day 1 and day 3 postfracture. Both TNF-alpha and IL-1alpha expression were localized primarily in macrophages and inflammatory cells during the early periods of inflammation and seen in mesenchymal and osteoblastic cells later during healing. TNF-alpha expression also was detected at very high levels in hypertrophic chondrocytes. These data imply that the expression profiles for OPG, RANKL, and M-CSF are tightly coupled during fracture healing and involved in the regulation of both endochondral resorption and bone remodeling. TNF-alpha and IL-1 are expressed at both very early and late phases in the repair process, which suggests that these cytokines are important in the initiation of the repair process and play important functional roles in intramembraneous bone formation and trabecular bone remodeling.

Hepatocyte responses to volatile anesthetics: changes in surface scanning and enzyme leakage.

The effects of volatile anesthetics were assessed in freshly isolated rat hepatocytes by surface-scanning electron microscopy and by measuring leakage of cellular enzymes, lactate dehydrogenase and beta-glucuronidase into the surrounding medium. The order of potency in regard to their capacity to produce alterations of these parameters was halothane = methoxyflurane greater than ether = control. The extent of enzyme leakage from hepatocytes exposed to halothane or methoxyflurane was both dose dependent and, for the first 30 minutes, time dependent. Surface scanning of the isolated hepatocytes showed that both halothane and methoxyflurane produced enzyme leakage and morphologic changes in cellular membranes, but ether did not. These studies demonstrate that scanning electron microscopy and enzyme leakage from cells are useful for the evaluation of drug-induced changes in lever cells in vitro. The relation between these drug-induced changes and clinical hepatotoxicity remains to be elucidated.